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THE LANCET
Authors Blessy Antony,a Hannah Blau,b Elena Casiraghi,c,d,e Johanna J. Loomba,f Tiffany J. Callahan,g Bryan J. Laraway,h Kenneth J. Wilkins,i Corneliu C. Antonescu,j Giorgio Valentini,c,e Andrew E. Williams,k Peter N. Robinson,b,l Justin T. Reese,d and T. M. Murali,a, on behalf of the N3C consortium
NATURE
Authors Jon Klein, Jamie Wood, Jillian Jaycox, Rahul M. Dhodapkar, Peiwen Lu, Jeff R. Gehlhausen, Alexandra Tabachnikova, Kerrie Greene, Laura Tabacof, Amyn A. Malik, Valter Silva Monteiro, Julio Silva, Kathy Kamath, Minlu Zhang, Abhilash Dhal, Isabel M. Ott, Gabrielee Valle, Mario Peña-Hernandez, Tianyang Mao, Bornali Bhattacharjee, Takehiro Takahashi, Carolina Lucas, Eric Song, Dayna Mccarthy, Erica Breyman, Jenna Tosto-Mancuso, Yile Dai, Emily Perotti, Koray Akduman, Tiffany J. Tzeng, Lan Xu, Anna C. Geraghty, Michelle Monje, Inci Yildirim, John Shon, Ruslan Medzhitov, Denyse Lutchmansingh, Jennifer D. Possick, Naftali Kaminski, Saad B. Omer, Harlan M. Krumholz, Leying Guan, Charles S. Dela Cruz, David van Dijk, Aaron M. Ring, David Putrino & Akiko Iwasaki
Post-acute infection syndromes (PAIS) may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a PAIS known as “Long COVID” (LC). Individuals with LC frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2–4; however, the biological processes associated with the development and persistence of these symptoms are unclear. Here, 273 individuals with or without LC were enrolled in a cross-sectional study that included multi-dimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with LC. Marked differences were noted in circulating myeloid and lymphocyte populations relative to matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with LC. Further, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with LC, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with LC. Integration of immune phenotyping data into unbiased machine learning models identified key features most strongly associated with LC status. Collectively, these findings may help guide future studies into the pathobiology of LC and aid in developing relevant biomarkers.
THE BMJ
Authors Andrew S Oseran,1,2 Yang Song,1 Jiaman Xu,1 Issa J Dahabreh,1,3 Rishi K Wadhera,1,4 James A de Lemos,5 Sandeep R Das,5 Tianyu Sun,1 Robert W Yeh,1,4 Dhruv S Kazi1,4
Objectives To characterize the long term risk of death and hospital readmission after an index admission with covid-19 among Medicare fee-for-service beneficiaries, and to compare these outcomes with historical control patients admitted to hospital with influenza. Design Retrospective cohort study. Setting United States. Participants 883394 Medicare fee-for-service beneficiaries age ≥65 years discharged alive after an index hospital admission with covid-19 between 1 March 2020 and 31 August 2022, compared with 56409 historical controls discharged alive after a hospital admission with influenza between 1 March 2018 and 31 August 2019. Weighting methods were used to account for differences in observed characteristics. Main outcome measures All cause death within 180 days of discharge. Secondary outcomes included first all cause readmission and a composite of death or readmission within 180 days. Results The covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference −0.12) and had a lower proportion of women (51.7% v 57.3%, −0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid- Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, −0.12), heart failure (43.4% v 49.9%, −0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, −0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;–0.1%, −0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%. Co nclusions Medicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.
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Authors Amy D. Proal, Michael B. VanElzakker, Soo Aleman, Katie Bach, Brittany P. Boribong, Marcus Buggert, Sara Cherry, Daniel S. Chertow, Helen E. Davies, Christopher L. Dupont, Steven G. Deeks, William Eimer, E. Wesley Ely, Alessio Fasano, Marcelo Freire, Linda N. Geng, Diane E. Griffin, Timothy J. Henrich, Akiko Iwasaki, David Izquierdo-Garcia, Michela Locci, Saurabh Mehandru, Mark M. Painter, Michael J. Peluso, Etheresia Pretorius, David A. Price, David Putrino, Richard H. Scheuermann, Gene S. Tan, Rudolph E. Tanzi, Henry F. VanBrocklin, Lael M. Yonker, E. John Wherry
Abstract Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA—potentially capable of being translated to produce viral proteins—persist in tissue as a ‘reservoir’. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.
JAMA
Authors Nancy Kentish-Barnes, PhD Matthieu Resche-Rigon, MD, PhD Antoine Lafarge Virginie Souppart, RN Anne Renet, MS Frédéric Pochard, MD, PhD Elie Azoulay
Authors Emily Harris
Authors Michelle K. Ptak, BA1; Elena Frank, PhD2; Katherine E. T. Ross, BS, BA1; Jennifer L. Cleary, MS1; Srijan Sen, MD, PhD3; Karina Pereira-Lima, PhD, MSc4
LANCET
Authors Franziska Legler,a,b,h Lil Meyer-Arndt,a,b,c,h Lukas Mödl,d Claudia Kedor,e Helma Freitag,e Elisa Stein,e Uta Hoppmann,a,b,c Rebekka Rust,a,b Kirsten Wittke,e Nadja Siebert,b Janina Behrens,b Andreas Thiel,f,g Frank Konietschke,d Friedemann Paul,a,b,h Carmen Scheibenbogen,e,h and Judith Bellmann-Strobla,b,h,∗
Authors Ryan C. Thompson, Nicole W. Simons, Lillian Wilkins, Esther Cheng, Diane Marie Del Valle, Gabriel E. Hoffman, Carlo Cervia, Brian Fennessy, Konstantinos Mouskas, Nancy J. Francoeur, Jessica S. Johnson, Lauren Lepow, Jessica Le Berichel, Christie Chang, Aviva G. Beckmann, Ying-chih Wang, Kai Nie, Nicholas Zaki, Kevin Tuballes, Vanessa Barcessat, Mario A. Cedillo, Dan Yuan, Laura Huckins, Panos Roussos, Thomas U. Marron, The Mount Sinai COVID-19 Biobank Team, Benjamin S. Glicksberg, Girish Nadkarni, James R. Heath, Edgar Gonzalez-Kozlova, Onur Boyman, Seunghee Kim-Schulze, Robert Sebra, Miriam Merad, Sacha Gnjatic, Eric E. Schadt, Alexander W. Charney, Noam D. Beckmann
Abstract Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.
Authors Melissa Suran
Authors Nathan J. Cheetham Rose Penfold Valentina Giunchiglia Vicky Bowyer Carole H. Sudre Liane S. Canas Jie Deng Benjamin Murray Eric Kerfoot Michela Antonelli Khaled Rjoob Erika Molteni Marc F. Österdahl Nicholas R. Harvey William R. Trender Michael H. Malim Katie J. Doores Peter J. Hellyer Marc Modat Alexander Hammers Sebastien Ourselin Emma L. Duncan Adam Hampshire Claire J. Steves
Authors Aarthi Talla, Suhas V. Vasaikar, Gregory Lee Szeto, Maria P. Lemos, Julie L. Czartoski, Hugh MacMillan, Zoe Moodie, Kristen W. Cohen, Lamar B. Fleming, Zachary Thomson, Lauren Okada, Lynne A. Becker, Ernest M. Coffey, Stephen C. De Rosa, Evan W. Newell, Peter J. Skene, Xiaojun Li, Thomas F. Bumol, M. Juliana McElrath & Troy R. Torgerson
Abstract Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute SARS-CoV-2 infection. The aetiologies may include persistent inflammation, unresolved tissue damage or delayed clearance of viral protein or RNA, but the biological differences they represent are not fully understood. Here we evaluate the serum proteome in samples, longitudinally collected from 55 PASC individuals with symptoms lasting ≥60 days after onset of acute infection, in comparison to samples from symptomatically recovered SARS-CoV-2 infected and uninfected individuals. Our analysis indicates heterogeneity in PASC and identified subsets with distinct signatures of persistent inflammation. Type II interferon signaling and canonical NF-κB signaling (particularly associated with TNF), appear to be the most differentially enriched signaling pathways, distinguishing a group of patients characterized also by a persistent neutrophil activation signature. These findings help to clarify biological diversity within PASC, identify participants with molecular evidence of persistent inflammation, and highlight dominant pathways that may have diagnostic or therapeutic relevance, including a protein panel that we propose as having diagnostic utility for differentiating inflammatory and non-inflammatory PASC.
Authors Tanayott Thaweethai, PhD; Sarah E. Jolley, MD, MS; Elizabeth W. Karlson, MD, MS; Emily B. Levitan, ScD; Bruce Levy, MD; Grace A. McComsey, MD; Lisa McCorkell, MPP; Girish N. Nadkarni, MD, MPH; Sairam Parthasarathy, MD; Upinder Singh, MD; Tiffany A. Walker, MD; Caitlin A. Selvaggi, MS; Daniel J. Shinnick, MS; Carolin C. M. Schulte, PhD; Rachel Atchley-Challenner, PhD; RECOVER Consortium Authors; Leora I. Horwitz, MD; Andrea S. Foulkes, ScD; for the RECOVER Consortium
Abstract Importance SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure SARS-CoV-2 infection. Main Outcomes and Measures PASC and 44 participant-reported symptoms (with severity thresholds). Results A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
THE NEW ENGLAND JOURNAL OF MEDICINE
Authors Janko Ž. Nikolich, M.D., Ph.D., Clifford J. Rosen, M.D.
Authors Cristina Groza, David Totschnig, Christoph Wenisch, Johanna Atamaniuk, Alexander Zoufaly
Abstract The causative agent of the ongoing Corona virus disease 2019 (COVID-19) pandemic, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has acquired a considerable amount of mutations, leading to changes in clinical manifestations and increased transmission. Recent studies based on animal disease models and data from the general population were reporting a higher pathogenicity of the BA.2 sublineage compared to BA.1. The aim of this study was to provide real world data on patients with the SARS-CoV-2 Omicron BA.1 and BA.2 subvariants treated at our center, highlighting similarities and differences in the clinical disease course. We retrospectively collected and analyzed the data of adult patients admitted with confirmed SARS-CoV-2 infection at the Department for Infectious Diseases and Tropical Medicine, Klinik Favoriten, Vienna, Austria. Patient characteristics including age, underlying diseases, vaccination status and outcome were compared between patients with the BA.1 and BA.2 subvariants. Between January 2022 and May 2022 we included 168 patients infected with Omicron BA.1 and 100 patients with BA.2. Patients admitted with BA.2 were significantly older, more often fully immunized and required less dexamethasone than patients with BA.1. No substantial differences were identified between patients infected with BA.1 and BA.2 regarding BMI, laboratory findings, need for supplemental oxygen, mortality and other evaluated comorbidities excepting active malignancies. The significantly larger percentage of fully immunized patients admitted with BA.2 is pointing to an increased transmissibility of this subvariant, while the comparable outcome of a somewhat older and sicker patient population might be indicative of reduced virulence.
Authors Yan Xie, Taeyoung Choi, Ziyad Al-Aly
Authors Hiam Chemaitelly, Houssein H Ayoub, Patrick Tang, Peter Coyle, Hadi M Yassine, Asmaa A Al Thani, Hebah A Al-Khatib, Mohammad R Hasan, Zaina Al-Kanaani, Einas Al-Kuwari, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, Riyazuddin Mohammad Shaik, Hanan F Abdul-Rahim, Gheyath K Nasrallah, Mohamed Ghaith Al-Kuwari, Adeel A Butt, Hamad Eid Al-Romaihi, Mohamed H Al-Thani, Abdullatif Al-Khal, Roberto Bertollini, Jeremy Samuel Faust, Laith J Abu-Raddad
Authors Mark É. Czeisler, Said A. Ibrahim
Authors Christopher Doan, BS; Shuang Li, PhD; James S. Goodwin
Abstract Importance Several studies reported sharp decreases in screening mammography for breast cancer and low-dose computed tomographic screening for lung cancer in the early months of the COVID-19 pandemic, followed by a return to normal or near-normal levels in the summer of 2020. Objective To determine the observed vs expected mammography and low-dose computed tomographic scan rates from the beginning of the pandemic through April 2022. Design, Setting, and Participants In this retrospective cohort study assessing mammography and low-dose computed tomography rates from January 2017 through April 2022, data for January 2016 to February 2020 were used to generate expected rates for the period March 2020 to April 2022. The study included a 20% national sample of Medicare fee-for-service enrollees among women aged 50 to 74 years for mammography, and men and women aged 55 to 79 years for low-dose computed tomographic scan. Main Outcomes and Measures Receipt of screening mammography or low-dose computed tomographic scan. Results The yearly cohorts for the mammography rates included more than 1 600 000 women aged 50 to 74 years, and the cohorts for the low-dose computed tomographic scan rates included more than 3 700 000 men and women aged 55 to 79 years. From January 2017 through February 2020, monthly mammography rates were flat, whereas there was a monotonic increase in low-dose computed tomographic scan rates, from approximately 500 per million per month in early 2017 to 1100 per million per month by January 2020. Over the period from March 2020 to April 2022, there were episodic drops in both mammography and low-dose computed tomographic scan rates, coincident with increases in national COVID-19 infection rates. For the periods from March 2020 to February 2020 and March 2021 to February 2022, the observed low-dose computed tomographic scan rates were 24% (95% CI, 23%-24%) and 14% (95% CI, 13%-15%) below expected rates, whereas mammography rates were 17% (95% CI, 17%-18%) and 4% (95% CI, 4%-3%) below expected. Conclusions and Relevance In this cohort study, the decreases in cancer screening during the early phases of the COVID-19 pandemic did not resolve after the initial pandemic surges. Successful interventions to improve screening rates should address pandemic-specific reasons for low screening participation.
Authors Seth Flaxman, PhD; Charles Whittaker, PhD; Elizaveta Semenova, PhD; Theo Rashid, MSci; Robbie M. Parks, PhD; Alexandra Blenkinsop, PhD; H. Juliette T. Unwin, PhD; Swapnil Mishra, PhD; Samir Bhatt, DPhil; Deepti Gurdasani, PhD; Oliver Ratmann
Abstract Importance COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. Objective To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. Design, Setting, and Participants This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non–COVID-19 causes in 2019, 2020, and 2021. Main Outcomes and Measures Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). Results There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US, ranking eighth among all causes of deaths, fifth in disease-related causes of deaths (excluding unintentional injuries, assault, and suicide), and first in deaths caused by infectious or respiratory diseases when compared with 2019. COVID-19 deaths constituted 2% of all causes of death in this age group. Conclusions and Relevance The findings of this study suggest that COVID-19 was a leading cause of death in CYP. It caused substantially more deaths in CYP annually than any vaccine-preventable disease historically in the recent period before vaccines became available. Various factors, including underreporting and not accounting for COVID-19’s role as a contributing cause of death from other diseases, mean that these estimates may understate the true mortality burden of COVID-19. The findings of this study underscore the public health relevance of COVID-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, appropriate pharmaceutical and nonpharmaceutical interventions (eg, vaccines, ventilation, air cleaning) will continue to play an important role in limiting transmission of the virus and mitigating severe disease in CYP.
Authors Hannah E. Davis, Lisa McCorkell, Julia Moore Vogel, Eric J. Topol
Abstract Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.
Authors Evan Xu, Yan Xie, Ziyad Al-Aly
Authors Peije Russell, Lars Esser, Christoph E. Hagemeyer & Nicolas H. Voelcker
Abstract Extensive reports of pulmonary embolisms, ischaemic stroke and myocardial infarctions caused by coronavirus disease 2019 (COVID-19), as well as a significantly increased long-term risk of cardiovascular diseases in COVID-19 survivors, have highlighted severe deficiencies in our understanding of thromboinflammation and the need for new therapeutic options. Due to the complexity of the immunothrombosis pathophysiology, the efficacy of treatment with conventional anti-thrombotic medication is questioned. Thrombolytics do appear efficacious, but are hindered by severe bleeding risks, limiting their use. Nanomedicine can have profound impact in this context, protecting delicate (bio)pharmaceuticals from degradation en route and enabling delivery in a targeted and on demand manner. We provide an overview of the most promising nanocarrier systems and design strategies that may be adapted to develop nanomedicine for COVID-19-induced thromboinflammation, including dual-therapeutic approaches with antiviral and immunosuppressants. Resultant targeted and side-effect-free treatment may aid greatly in the fight against the ongoing COVID-19 pandemic.
Authors Theresa M. Bastain, PhD, MPH; Emily A. Knapp, PhD; Andrew Law, ScM; Molly Algermissen, PhD; Lyndsay A. Avalos, PhD; Zoe Birnhak, BA; Courtney Blackwell, PhD; Carrie V. Breton, ScD; Cristiane Duarte, PhD; Jean Frazier, MD; Jody Ganiban, PhD; Paige Greenwood, PhD; Julie Herbstman, PhD; Ixel Hernandez-Castro, MPH; Julie Hofheimer, PhD; Margaret R. Karagas, PhD; Johnnye Lewis, PhD; David Pagliaccio, PhD; Bruce Ramphal, BS; Darby Saxbe, PhD; Rebecca Schmidt, PhD; Carmen Velez-Vega, PhD; Xiaodan Tang, PhD; Ghassan B. Hamra, PhD; Amy Margolis
Abstract Importance The primary outcomes of the COVID-19 pandemic on the mental health of women with children remain largely unknown. Objectives To identify and describe clusters of mothers of children participating in the Environmental influences on Child Health Outcomes (ECHO) Program that characterize pandemic-associated hardships, coping mechanisms, and behaviors, and to evaluate associations between pandemic-associated hardships, coping strategies, and behavior changes with pandemic-associated traumatic stress symptoms. Design, Setting, and Participants This multicenter cohort study investigated experiences during the COVID-19 pandemic between April 2020 and August 2021 among maternal caregivers of children participating in the ECHO Program. Data from self-identified mothers of ECHO-enrolled children from 62 US cohorts were included in analyses. Data were analyzed from November 2021 to July 2022. Exposures The primary exposures were pandemic-associated changes in mothers’ health, health care utilization, work and finances, coping strategies, and health-associated behaviors. Exposures were assessed via a self-reported questionnaire designed by ECHO investigators. Main Outcomes and Measures The primary outcome was the total symptoms score of pandemic-associated traumatic stress (PTS), defined as the number of items endorsed at least sometimes or more frequently, from a 10-item self-report measure. Results The study surveyed 11 473 mothers (mean [SD] age, 37.8 [7.4] years; 342 American Indian [2.98%], 378 Asian [3.29%], 1701 Black [14.83%], and 7195 White [62.71%]; 2184 with Hispanic/Latina ethnicity [19.04%]) and identified 2 clusters that best characterized their COVID-19 pandemic experiences—one characterized by higher life disruptions (eg, to work and health care), higher social isolation, more coping behaviors to mitigate the outcomes of the pandemic, and more changes to their health behavior routines (high change [1031 mothers]) and the other characterized by lower changes (low change [3061 mothers]). The high change cluster was more socioeconomically advantaged and reported higher PTS (mean [SD] number of symptoms, 3.72 [2.44] vs 2.51 [2.47]). Across both clusters, higher pandemic-associated hardships, coping mechanisms, and behavior changes were associated with higher PTS, and these associations were greater in the low change cluster. Conclusions and Relevance In this study of more than 11 000 US mothers, associations between socioeconomic factors, stressful life events, and mental health sequelae were complex. Accordingly, programs, policies, and practices targeting mental health during public health crises such as the COVID-19 pandemic should consider the range and configuration of hardships in designing the most effective interventions to mitigate long-term outcomes.
Authors Victoria Mansell, Sally Hall Dykgraaf, Michael Kidd, Felicity Goodyear-Smith
Authors Alessandro Padovani, Andrea Pilotto
Authors Paul Baum, Lisa Do, Lea Deterding, Julia Lier, Ines Kunis, Dorothee Saur, Joseph Classen, Hubert Wirtz & Ulrich Laufs
Abstract Patients with Post-COVID syndrome (PCS) are frequently referred for cardiologic evaluation. We assessed cardiac function and biomarkers in relation to functional status and fatigue in patients with PCS. This prospective single-center cohort study included 227 patients with persisting symptoms after COVID-19 infection. Most frequent complaints were fatigue (70%), dyspnea (56%), neurocognitive symptoms (34%) and chest pain (28%). Standardized questionnaires were used to assess Post-COVID-Functional-Scale (PCFS) and fatigue (MFI-20). The fatigue severity was inversely related to age and did not correlate with cardiovascular diseases, echocardiographic findings, or biomarkers. Similarly, mild to moderate functional impairment (PCFS 1–3) did not correlate with cardiovascular alterations. However, the subgroup of patients with significant functional impairment (PCFS = 4) had more frequent cardiovascular comorbidities, biomarkers and impaired global longitudinal strain (GLS). Patients with elevated troponin T showed abnormal GLS, reduced left ventricular ejection fraction and impaired tricuspid annular plane systolic excursion. The majority of patients with PCS shows a normal cardiac function. Only the small subgroup of patients with severe functional impairment and patients with elevated troponin T is at risk for impaired cardiac function and likely to benefit from specialized care by a cardiologist.
Authors Chris Stokel-Walker
Authors Varun Venkataramani, M.D., Ph.D., and Frank Winkler
Authors Tom Alan Ranger, PhD; Ash Kieran Clift, MBBS; Martina Patone, PhD; Carol A. C. Coupland, PhD; Robert Hatch, BM, BCh; Karen Thomas, MSc; Peter Watkinson, MD; Julia Hippisley-Cox
Abstract Importance Evidence indicates that preexisting neuropsychiatric conditions confer increased risks of severe outcomes from COVID-19 infection. It is unclear how this increased risk compares with risks associated with other severe acute respiratory infections (SARIs). Objective To determine whether preexisting diagnosis of and/or treatment for a neuropsychiatric condition is associated with severe outcomes from COVID-19 infection and other SARIs and whether any observed association is similar between the 2 outcomes. Design, Setting, and Participants Prepandemic (2015-2020) and contemporary (2020-2021) longitudinal cohorts were derived from the QResearch database of English primary care records. Adjusted hazard ratios (HRs) with 99% CIs were estimated in April 2022 using flexible parametric survival models clustered by primary care clinic. This study included a population-based sample, including all adults in the database who had been registered with a primary care clinic for at least 1 year. Analysis of routinely collected primary care electronic medical records was performed. Exposures Diagnosis of and/or medication for anxiety, mood, or psychotic disorders and diagnosis of dementia, depression, schizophrenia, or bipolar disorder. Main Outcomes and Measures COVID-19–related mortality, or hospital or intensive care unit admission; SARI-related mortality, or hospital or intensive care unit admission. Results The prepandemic cohort comprised 11 134 789 adults (223 569 SARI cases [2.0%]) with a median (IQR) age of 42 (29-58) years, of which 5 644 525 (50.7%) were female. The contemporary cohort comprised 8 388 956 adults (58 203 severe COVID-19 cases [0.7%]) with a median (IQR) age of 48 (34-63) years, of which 4 207 192 were male (50.2%). Diagnosis and/or treatment for neuropsychiatric conditions other than dementia was associated with an increased likelihood of a severe outcome from SARI (anxiety diagnosis: HR, 1.16; 99% CI, 1.13-1.18; psychotic disorder diagnosis and treatment: HR, 2.56; 99% CI, 2.40-2.72) and COVID-19 (anxiety diagnosis: HR, 1.16; 99% CI, 1.12-1.20; psychotic disorder treatment: HR, 2.37; 99% CI, 2.20-2.55). The effect estimate for severe outcome with dementia was higher for those with COVID-19 than SARI (HR, 2.85; 99% CI, 2.71-3.00 vs HR, 2.13; 99% CI, 2.07-2.19). Conclusions and Relevance In this longitudinal cohort study, UK patients with preexisting neuropsychiatric conditions and treatments were associated with similarly increased risks of severe outcome from COVID-19 infection and SARIs, except for dementia.
Authors Judith D Auerbach, Andrew D Forsyth, Calum Davey, James R Hargreaves, the Group for lessons from pandemic HIV prevention for the COVID-19 response
Authors Sydney M. Hartman-Munick, MD; Jessica A. Lin, MD; Carly E. Milliren, MPH; Paula K. Braverman, MD; Kathryn S. Brigham, MD; Martin M. Fisher, MD; Neville H. Golden, MD; Jessica M. Jary, DO; Diana C. Lemly, MD; Abigail Matthews, PhD, MHA; Rollyn M. Ornstein, MD; Alexandra Roche, MD; Ellen S. Rome, MD, MPH; Elaine L. Rosen, MD; Yamini Sharma, MD; Jennifer K. Shook, MD; Jaime L. Taylor, DO, MS; Margaret Thew, DNP, FNP; Megen Vo, MD; Michaela Voss, MD; Elizabeth R. Woods, MD, MPH; Sara F. Forman, MD; Tracy K. Richmond,
Abstract Importance The COVID-19 pandemic has affected youth mental health. Increases in site-specific eating disorder (ED) care have been documented; however, multisite studies demonstrating national trends are lacking. Objective To compare the number of adolescent/young adult patients seeking inpatient and outpatient ED care before and after onset of the COVID-19 pandemic. Design, Setting, and Participants Using an observational case series design, changes in volume in inpatient and outpatient ED-related care across 15 member sites (14 geographically diverse hospital-based adolescent medicine programs and 1 nonhospital-based ED program) of the US National Eating Disorder Quality Improvement Collaborative was examined. Sites reported monthly volumes of patients seeking inpatient and outpatient ED care between January 2018 and December 2021. Patient volumes pre- and postpandemic onset were compared separately for inpatient and outpatient settings. Demographic data such as race and ethnicity were not collected because this study used monthly summary data. Exposures Onset of the COVID-19 pandemic. Main Outcomes and Measures Monthly number of patients seeking inpatient/outpatient ED-related care. Results Aggregate total inpatient ED admissions were 81 in January 2018 and 109 in February 2020. Aggregate total new outpatient assessments were 195 in January 2018 and 254 in February 2020. Before the COVID-19 pandemic, the relative number of pooled inpatient ED admissions were increasing over time by 0.7% per month (95% CI, 0.2%-1.3%). After onset of the pandemic, there was a significant increase in admissions over time of 7.2% per month (95% CI, 4.8%-9.7%) through April 2021, then a decrease of 3.6% per month (95% CI, −6.0% to −1.1%) through December 2021. Prepandemic, pooled data showed relative outpatient ED assessment volume was stable over time, with an immediate 39.7% decline (95% CI, −50.4% to −26.7%) in April 2020. Subsequently, new assessments increased by 8.1% (95% CI, 5.3%-11.1%) per month through April 2021, then decreased by 1.5% per month (95% CI, −3.6% to 0.7%) through December 2021. The nonhospital-based ED program did not demonstrate a significant increase in the absolute number of admissions after onset of the pandemic but did see a significant increase of 8.2 (95% CI, 6.2-10.2) additional inquiries for care per month in the first year after onset of the pandemic. Conclusions and Relevance In this study, there was a significant COVID-19 pandemic-related increase in both inpatient and outpatient volume of patients with EDs across sites, particularly in the first year of the pandemic. Given inadequate ED care availability prior to the pandemic, the increased postpandemic demand will likely outstrip available resources. Results highlight the need to address ED workforce and program capacity issues as well as improve ED prevention strategies.
Authors Mallikarjuna Ponnapa Reddy 1, Ashwin Subramaniam 2, Clara Chua 3, Ryan Ruiyang Ling 4, Christopher Anstey 5, Kollengode Ramanathan 6, Arthur S Slutsky 7, Kiran Shekar
Authors Raphaela I. Lau, Fen Zhang, Qin Liu, Qi Su, Francis K. L. Chan, Siew C. Ng
Abstract The gastrointestinal tract is involved in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gut microbiota has important roles in viral entry receptor angiotensin-converting enzyme 2 (ACE2) expression, immune homeostasis, and crosstalk between the gut and lungs, the ‘gut–lung axis’. Emerging preclinical and clinical studies indicate that the gut microbiota might contribute to COVID-19 pathogenesis and disease outcomes; SARS-CoV-2 infection was associated with altered intestinal microbiota and correlated with inflammatory and immune responses. Here, we discuss the cutting-edge evidence on the interactions between SARS-CoV-2 infection and the gut microbiota, key microbial changes in relation to COVID-19 severity and host immune dysregulations with the possible underlying mechanisms, and the conceivable consequences of the pandemic on the human microbiome and post-pandemic health. Finally, potential modulatory strategies of the gut microbiota are discussed. These insights could shed light on the development of microbiota-based interventions for COVID-19.
Authors Raphael S Peter, senior associate researcher1, Alexandra Nieters, associate professor2, Hans-Georg Kräusslich, professor3, Stefan O Brockmann, head4, Siri Göpel, senior physician5, Gerhard Kindle, senior associate researcher2, Uta Merle, chief physician6, Jürgen M Steinacker, professor7, Dietrich Rothenbacher, professor1, Winfried V Kern
Abstract Objectives To describe symptoms and symptom clusters of post-covid syndrome six to 12 months after acute infection, describe risk factors, and examine the association of symptom clusters with general health and working capacity. Design Population based, cross sectional study Setting Adults aged 18-65 years with confirmed SARS-CoV-2 infection between October 2020 and March 2021 notified to health authorities in four geographically defined regions in southern Germany. Participants 50 457 patients were invited to participate in the study, of whom 12 053 (24%) responded and 11 710 (58.8% (n=6881) female; mean age 44.1 years; 3.6% (412/11 602) previously admitted with covid-19; mean follow-up time 8.5 months) could be included in the analyses. Main outcome measures Symptom frequencies (six to 12 months after versus before acute infection), symptom severity and clustering, risk factors, and associations with general health recovery and working capacity. Results The symptom clusters fatigue (37.2% (4213/11 312), 95% confidence interval 36.4% to 38.1%) and neurocognitive impairment (31.3% (3561/11 361), 30.5% to 32.2%) contributed most to reduced health recovery and working capacity, but chest symptoms, anxiety/depression, headache/dizziness, and pain syndromes were also prevalent and relevant for working capacity, with some differences according to sex and age. Considering new symptoms with at least moderate impairment of daily life and ≤80% recovered general health or working capacity, the overall estimate for post-covid syndrome was 28.5% (3289/11 536, 27.7% to 29.3%) among participants or at least 6.5% (3289/50 457) in the infected adult population (assuming that all non-responders had completely recovered). The true value is likely to be between these estimates. Conclusions Despite the limitation of a low response rate and possible selection and recall biases, this study suggests a considerable burden of self-reported post-acute symptom clusters and possible sequelae, notably fatigue and neurocognitive impairment, six to 12 months after acute SARS-CoV-2 infection, even among young and middle aged adults after mild infection, with a substantial impact on general health and working capacity.
Authors Nico Dragano, PhD; Olga Dortmann, Dipl; Jörg Timm, MD; Matthias Mohrmann, Dipl; Rosemarie Wehner, Dipl; Christoph J. Rupprecht, Dipl; Maria Scheider, MS; Ertan Mayatepek, MD; Morten Wahrendorf
Authors Mayssam Nehme, Olivia Braillard, François Chappuis, CoviCare Study Team, Idris Guessous
Abstract Post-COVID condition is prevalent in 10–35% of cases in outpatient settings, however a stratification of the duration and severity of symptoms is still lacking, adding to the complexity and heterogeneity of the definition of post-COVID condition and its oucomes. In addition, the potential impacts of a longer duration of disease are not yet clear, along with which risk factors are associated with a chronification of symptoms beyond the initial 12 weeks. In this study, follow-up was conducted at 7 and 15 months after testing at the outpatient SARS-CoV-2 testing center of the Geneva University Hospitals. The chronification of symptoms was defined as the continuous presence of symptoms at each evaluation timepoint (7 and 15 months). Adjusted estimates of healthcare utilization, treatment, functional impairment and quality of life were calculated. Logistic regression models were used to evaluate the associations between the chronification of symptoms and predictors. Overall 1383 participants were included, with a mean age of 44.3 years, standard deviation (SD) 13.4 years, 61.4% were women and 54.5% did not have any comorbidities. Out of SARS-CoV-2 positive participants (n = 767), 37.0% still had symptoms 7 months after their test of which 47.9% had a resolution of symptoms at the second follow-up (15 months after the infection), and 52.1% had persistent symptoms and were considered to have a chronification of their post-COVID condition. Individuals with a chronification of symptoms had an increased utilization of healthcare resources, more recourse to treatment, more functional impairment, and a poorer quality of life. Having several symptoms at testing and difficulty concentrating at 7 months were associated with a chronification of symptoms. COVID-19 patients develop post-COVID condition to varying degrees and duration. Individuals with a chronification of symptoms experience a long-term impact on their health status, functional capacity and quality of life, requiring a special attention, more involved care and early on identification considering the associated predictors.
Authors Eleni Gavriilaki, Styliani Kokoris
Authors Maxime Taquet, Rebecca Sillett, Lena Zhu, Jacob Mendel, Isabella Camplisson, Quentin Dercon, Paul J Harrison
Authors JACQUI WISE
Authors Christopher E Brightling, Rachael A Evans
SCIENCE
Authors Katharine M. N. Lee, Eleanor J. Junkins, Chongliang Luo, Urooba A. Fatima, Maria L. Cox, Kathryn B. H. Clancy
Abstract Early in 2021, many people began sharing that they experienced unexpected menstrual bleeding after SARS-CoV-2 inoculation. We investigated this emerging phenomenon of changed menstrual bleeding patterns among a convenience sample of currently and formerly menstruating people using a web-based survey. In this sample, 42% of people with regular menstrual cycles bled more heavily than usual, while 44% reported no change after being vaccinated. Among respondents who typically do not menstruate, 71% of people on long-acting reversible contraceptives, 39% of people on gender-affirming hormones, and 66% of postmenopausal people reported breakthrough bleeding. We found that increased/breakthrough bleeding was significantly associated with age, systemic vaccine side effects (fever and/or fatigue), history of pregnancy or birth, and ethnicity. Generally, changes to menstrual bleeding are not uncommon or dangerous, yet attention to these experiences is necessary to build trust in medicine.
Authors Vignesh Chidambaram Amudha Kumar Marie Gilbert Majella Bhavna Seth Ranjith Kumar Sivakumar Dinesh Voruganti Mahesh Bavineni Ahmad Baghal Kim Gates Annu Kumari Subhi J. Al'Aref Panagis Galiatsatos Petros C. Karakousis Jawahar L. Mehta
Authors AA.VV.
Abstract A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days post-virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
Authors Dominique Farge*, Corinne Frere*, Jean M Connors, Alok A Khorana, Ajay Kakkar, Cihan Ay, Andres Muñoz, Benjamin Brenner, Pedro H Prata, Dialina Brilhante, Darko Antic, Patricia Casais, María Cecilia Guillermo Esposito, Takayuki Ikezoe, Syed A Abutalib, Luis A Meillon-García, Henri Bounameaux, Ingrid Pabinger, James Douketis, the International Initiative on Thrombosis and Cancer (ITAC) advisory panel
Authors Peymané Adab, Shamil Haroon, Margaret E O’Hara, Rachel E Jordan
Authors Bridget M. Kuehn
Authors Stéphane Kremer, H. Rolf Jäger
Authors Matthew Whitaker, Joshua Elliott, Marc Chadeau-Hyam, Steven Riley, Ara Darzi, Graham Cooke, Helen Ward, Paul Elliott
Abstract Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3–5 of the REACT-2 study (n = 508,707; September 2020 – February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3–5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3–5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.
Authors Ingibjörg Magnúsdóttir*, Anikó Lovik*, Anna Bára Unnarsdóttir*, Daniel McCartney*, Helga Ask*, Kadri Kõiv*, Lea Arregui Nordahl Christoffersen*, Sverre Urnes Johnson*, Arna Hauksdóttir, Chloe Fawns-Ritchie, Dorte Helenius, Juan González-Hijón, Li Lu, Omid V Ebrahimi, Asle Hoffart, David J Porteous, Fang Fang, Jóhanna Jakobsdóttir, Kelli Lehto, Ole A Andreassen, Ole B V Pedersen, Thor Aspelund, Unnur Anna Valdimarsdóttir
Authors Randy L. Gollub
Authors AMBER DANCE
Authors Melanie Saville, Jakob P. Cramer, Matthew Downham, Adam Hacker, Nicole Lurie, Lieven Van der Veken, Mike Whelan, Richard Hatchett
Authors Jennifer Abassi
Authors COVID-19 Forecasting Team
Authors Yan Xie, Evan Xu, Ziyad Al-Aly
Abstract Objective To estimate the risks of incident mental health disorders in survivors of the acute phase of covid-19. Design Cohort study. Setting US Department of Veterans Affairs. Participants Cohort comprising 153 848 people who survived the first 30 days of SARS-CoV-2 infection, and two control groups: a contemporary group (n=5 637 840) with no evidence of SARS-CoV-2, and a historical control group (n=5 859 251) that predated the covid-19 pandemic. Main outcomes measures Risks of prespecified incident mental health outcomes, calculated as hazard ratio and absolute risk difference per 1000 people at one year, with corresponding 95% confidence intervals. Predefined covariates and algorithmically selected high dimensional covariates were used to balance the covid-19 and control groups through inverse weighting. Results The covid-19 group showed an increased risk of incident anxiety disorders (hazard ratio 1.35 (95% confidence interval 1.30 to 1.39); risk difference 11.06 (95% confidence interval 9.64 to 12.53) per 1000 people at one year), depressive disorders (1.39 (1.34 to 1.43); 15.12 (13.38 to 16.91) per 1000 people at one year), stress and adjustment disorders (1.38 (1.34 to 1.43); 13.29 (11.71 to 14.92) per 1000 people at one year), and use of antidepressants (1.55 (1.50 to 1.60); 21.59 (19.63 to 23.60) per 1000 people at one year) and benzodiazepines (1.65 (1.58 to 1.72); 10.46 (9.37 to 11.61) per 1000 people at one year). The risk of incident opioid prescriptions also increased (1.76 (1.71 to 1.81); 35.90 (33.61 to 38.25) per 1000 people at one year), opioid use disorders (1.34 (1.21 to 1.48); 0.96 (0.59 to 1.37) per 1000 people at one year), and other (non-opioid) substance use disorders (1.20 (1.15 to 1.26); 4.34 (3.22 to 5.51) per 1000 people at one year). The covid-19 group also showed an increased risk of incident neurocognitive decline (1.80 (1.72 to 1.89); 10.75 (9.65 to 11.91) per 1000 people at one year) and sleep disorders (1.41 (1.38 to 1.45); 23.80 (21.65 to 26.00) per 1000 people at one year). The risk of any incident mental health diagnosis or prescription was increased (1.60 (1.55 to 1.66); 64.38 (58.90 to 70.01) per 1000 people at one year). The risks of examined outcomes were increased even among people who were not admitted to hospital and were highest among those who were admitted to hospital during the acute phase of covid-19. Results were consistent with those in the historical control group. The risk of incident mental health disorders was consistently higher in the covid-19 group in comparisons of people with covid-19 not admitted to hospital versus those not admitted to hospital for seasonal influenza, admitted to hospital with covid-19 versus admitted to hospital with seasonal influenza, and admitted to hospital with covid-19 versus admitted to hospital for any other cause. Conclusions The findings suggest that people who survive the acute phase of covid-19 are at increased risk of an array of incident mental health disorders. Tackling mental health disorders among survivors of covid-19 should be a priority.
Authors Torri D. Metz, Rebecca G. Clifton, Brenna L. Hughes, Grecio J. Sandoval, William A. Grobman, George R. Saade, Tracy A. Manuck, Monica Longo, Amber Sowles, Kelly Clark, Hyagriv N. Simhan, Dwight J. Rouse, Hector Mendez-Figueroa, Cynthia Gyamfi-Bannerman, Jennifer L. Bailit, Maged M. Costantine, Harish M. Sehdev, Alan T. N. Tita, George A. Macones
Abstract Importance It remains unknown whether SARS-CoV-2 infection specifically increases the risk of serious obstetric morbidity. Objective To evaluate the association of SARS-CoV-2 infection with serious maternal morbidity or mortality from common obstetric complications. Design, Setting, and Participants Retrospective cohort study of 14 104 pregnant and postpartum patients delivered between March 1, 2020, and December 31, 2020 (with final follow-up to February 11, 2021), at 17 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Gestational Research Assessments of COVID-19 (GRAVID) Study. All patients with SARS-CoV-2 were included and compared with those without a positive SARS-CoV-2 test result who delivered on randomly selected dates over the same period. Exposures SARS-CoV-2 infection was based on a positive nucleic acid or antigen test result. Secondary analyses further stratified those with SARS-CoV-2 infection by disease severity. Main Outcomes and Measures The primary outcome was a composite of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2. The main secondary outcome was cesarean birth. Results Of the 14 104 included patients (mean age, 29.7 years), 2352 patients had SARS-CoV-2 infection and 11 752 did not have a positive SARS-CoV-2 test result. Compared with those without a positive SARS-CoV-2 test result, SARS-CoV-2 infection was significantly associated with the primary outcome (13.4% vs 9.2%; difference, 4.2% [95% CI, 2.8%-5.6%]; adjusted relative risk [aRR], 1.41 [95% CI, 1.23-1.61]). All 5 maternal deaths were in the SARS-CoV-2 group. SARS-CoV-2 infection was not significantly associated with cesarean birth (34.7% vs 32.4%; aRR, 1.05 [95% CI, 0.99-1.11]). Compared with those without a positive SARS-CoV-2 test result, moderate or higher COVID-19 severity (n = 586) was significantly associated with the primary outcome (26.1% vs 9.2%; difference, 16.9% [95% CI, 13.3%-20.4%]; aRR, 2.06 [95% CI, 1.73-2.46]) and the major secondary outcome of cesarean birth (45.4% vs 32.4%; difference, 12.8% [95% CI, 8.7%-16.8%]; aRR, 1.17 [95% CI, 1.07-1.28]), but mild or asymptomatic infection (n = 1766) was not significantly associated with the primary outcome (9.2% vs 9.2%; difference, 0% [95% CI, −1.4% to 1.4%]; aRR, 1.11 [95% CI, 0.94-1.32]) or cesarean birth (31.2% vs 32.4%; difference, −1.4% [95% CI, −3.6% to 0.8%]; aRR, 1.00 [95% CI, 0.93-1.07]). Conclusions and Relevance Among pregnant and postpartum individuals at 17 US hospitals, SARS-CoV-2 infection was associated with an increased risk for a composite outcome of maternal mortality or serious morbidity from obstetric complications.
PLOS MEDICINE
Authors Krishnan Bhaskaran ,Christopher T. Rentsch ,George Hickman ,William J. Hulme ,Anna Schultze,Helen J. Curtis,Kevin Wing,Charlotte Warren-Gash,Laurie Tomlinson,Chris J. Bates,Rohini Mathur,Brian MacKenna,Viyaasan Mahalingasivam,Angel Wong,Alex J. Walker,Caroline E. Morton,Daniel Grint,Amir Mehrkar,Rosalind M. Eggo,Peter Inglesby,Ian J. Douglas,Helen I. McDonald,Jonathan Cockburn,Elizabeth J. Williamson,David Evans,John Parry,Frank Hester,Sam Harper,Stephen JW Evans,Sebastian Bacon,Liam Smeeth ,Ben Goldacre
Abstract Background There is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation. Methods and findings With the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes. We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants. Conclusions In this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.
Authors Bryan Christie
Authors Qiuyue Ma, Jue Liu, Qiao Liu, Liangyu Kang, Runqing Liu, Wenzhan Jing, Yu Wu, Min Liu
Abstract Importance Asymptomatic infections are potential sources of transmission for COVID-19. Objective To evaluate the percentage of asymptomatic infections among individuals undergoing testing (tested population) and those with confirmed COVID-19 (confirmed population). Data Sources PubMed, EMBASE, and ScienceDirect were searched on February 4, 2021. Study Selection Cross-sectional studies, cohort studies, case series studies, and case series on transmission reporting the number of asymptomatic infections among the tested and confirmed COVID-19 populations that were published in Chinese or English were included. Data Extraction and Synthesis This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Random-effects models were used to estimate the pooled percentage and its 95% CI. Three researchers performed the data extraction independently. Main Outcomes and Measures The percentage of asymptomatic infections among the tested and confirmed populations. Results Ninety-five unique eligible studies were included, covering 29 776 306 individuals undergoing testing. The pooled percentage of asymptomatic infections among the tested population was 0.25% (95% CI, 0.23%-0.27%), which was higher in nursing home residents or staff (4.52% [95% CI, 4.15%-4.89%]), air or cruise travelers (2.02% [95% CI, 1.66%-2.38%]), and pregnant women (2.34% [95% CI, 1.89%-2.78%]). The pooled percentage of asymptomatic infections among the confirmed population was 40.50% (95% CI, 33.50%-47.50%), which was higher in pregnant women (54.11% [95% CI, 39.16%-69.05%]), air or cruise travelers (52.91% [95% CI, 36.08%-69.73%]), and nursing home residents or staff (47.53% [95% CI, 36.36%-58.70%]). Conclusions and Relevance In this meta-analysis of the percentage of asymptomatic SARS-CoV-2 infections among populations tested for and with confirmed COVID-19, the pooled percentage of asymptomatic infections was 0.25% among the tested population and 40.50% among the confirmed population. The high percentage of asymptomatic infections highlights the potential transmission risk of asymptomatic infections in communities.
Authors Abdul Mannan Baig
Authors Yan Xie, Benjamin Bowe, Ziyad Al-Aly
Abstract The Post-Acute Sequelae of SARS-CoV-2 infection (PASC) have been characterized; however, the burden of PASC remains unknown. Here we used the healthcare databases of the US Department of Veterans Affairs to build a cohort of 181,384 people with COVID-19 and 4,397,509 non-infected controls and estimated that burden of PASC—defined as the presence of at least one sequela in excess of non-infected controls—was 73.43 (72.10, 74.72) per 1000 persons at 6 months. Burdens of individual sequelae varied by demographic groups (age, race, and sex) but were consistently higher in people with poorer baseline health and in those with more severe acute infection. In sum, the burden of PASC is substantial; PASC is non-monolithic with sequelae that are differentially expressed in various population groups. Collectively, our results may be useful in informing health systems capacity planning and care strategies of people with PASC.
Authors Martina Patone, Lahiru Handunnetthi, Defne Saatci, Jiafeng Pan, Srinivasa Vittal Katikireddi, Saif Razvi, David Hunt, Xue W. Mei, Sharon Dixon, Francesco Zaccardi, Kamlesh Khunti, Peter Watkinson, Carol A. C. Coupland, James Doidge, David A. Harrison, Rommel Ravanan, Aziz Sheikh, Chris Robertson, Julia Hippisley-Cox
Abstract Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain–Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12–1.71 at 15–21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain–Barré syndrome (IRR, 2.32; 95% CI: 1.08–5.02 at 1–28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18). Overall, we estimated 38 excess cases of Guillain–Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.
Authors Thirumalaisamy P. Velavana, Srinivas Reddy Pallerla, Jule Ruter, Yolanda Augustin, Peter G. Kremsner, Sanjeev Krishna, Christian G. Meyera
Abstract The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing.
Authors OFFICE PRESS THE LANCET
Authors Lixue Huang, Qun Yao, Xiaoying Gu, Qiongya Wang, Lili Ren, Yeming Wang, Ping Hu, Li Guo, Min Liu, Jiuyang Xu, Xueyang Zhang, Yali Qu, Yanqing Fan, Xia Li, Caihong Li, Ting Yu, Jiaan Xia, Ming Wei, Li Chen, Yanping Li, Fan Xiao, Dan Liu, Jianwei Wang, Xianguang Wang, Bin Cao
Authors Harry Crook, Sanara Raza, Joseph Nowell, Megan Young, Paul Edison
Abstract Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.
ELSEVIER
Authors Annemieke Smorenberg, Edgar JG Peters, Paul LA van Daele, Esther J Nossent, Majon Muller
Abstract Importance: Among COVID-19 cases, especially the (frail) elderly show a high number of severe infections, hospital admissions, complications, and death. The highest mortality is found between 80 and 89 years old. Why do these patients have a higher risk of severe COVID-19? In this narrative review we address potential mechanisms regarding viral transmission, physical reserve and the immune system, increasing the severity of this infection in elderly patients. Observations: First, the spread of COVID-19 may be enhanced in elderly patients. Viral shedding may be increased, and early identification may be complicated due to atypical disease presentation and limited testing capacity. Applying hygiene and quarantine measures, especially in patients with cognitive disorders including dementia, can be challenging. Additionally, elderly patients have a decreased cardiorespiratory reserve and are more likely to have co-morbidity including atherosclerosis, rendering them more susceptible to complications. The aging innate and adaptive immune system is weakened, while there is a pro-inflammatory tendency. The effects of SARS-CoV-2 on the immune system on cytokine production and T-cells, further seem to aggravate this pro-inflammatory tendency, especially in patients with cardiovascular comorbidity, increasing disease severity. Conclusions and relevance: The combination of all factors mentioned above contribute to the disease severity of COVID-19 in the older patient. While larger studies of COVID-19 in elderly patients are needed, understanding the factors increasing disease severity may improve care and preventative measures to protect the elderly patient at risk for (severe) COVID-19 in the future.
Authors Carole H Sudre, Ayya Keshet, Mark S Graham, Amit D Joshi, Smadar Shilo, Hagai Rossman, Benjamin Murray, Erika Molten, Kerstin Klaser, Liane D Canas, Michela Antonelli, Long H Nguyen, David A Drew, Marc Modat, Joan Capdevila Pujol, Sajaysurya Ganesh, Jonathan Wolf, Tomer Meir, Andrew T Chan, Claire J Steves, Tim D Spector, John S Brownstein, Eran Segal, Sebastien Ourselin, Christina M Astley
Authors Nicolas Barizien, Morgan Le Guen, Stéphanie Russel, Pauline Touche, Florent Huang, Alexandre Vallée
Abstract Increasing numbers of COVID-19 patients, continue to experience symptoms months after recovering from mild cases of COVID-19. Amongst these symptoms, several are related to neurological manifestations, including fatigue, anosmia, hypogeusia, headaches and hypoxia. However, the involvement of the autonomic nervous system, expressed by a dysautonomia, which can aggregate all these neurological symptoms has not been prominently reported. Here, we hypothesize that dysautonomia, could occur in secondary COVID-19 infection, also referred to as “long COVID” infection. 39 participants were included from December 2020 to January 2021 for assessment by the Department of physical medicine to enhance their physical capabilities: 12 participants with COVID-19 diagnosis and fatigue, 15 participants with COVID-19 diagnosis without fatigue and 12 control participants without COVID-19 diagnosis and without fatigue. Heart rate variability (HRV) during a change in position is commonly measured to diagnose autonomic dysregulation. In this cohort, to reflect HRV, parasympathetic/sympathetic balance was estimated using the NOL index, a multiparameter artificial intelligence-driven index calculated from extracted physiological signals by the PMD-200 pain monitoring system. Repeated-measures mixed-models testing group effect were performed to analyze NOL index changes over time between groups. A significant NOL index dissociation over time between long COVID-19 participants with fatigue and control participants was observed (p = 0.046). A trend towards significant NOL index dissociation over time was observed between long COVID-19 participants without fatigue and control participants (p = 0.109). No difference over time was observed between the two groups of long COVID-19 participants (p = 0.904). Long COVID-19 participants with fatigue may exhibit a dysautonomia characterized by dysregulation of the HRV, that is reflected by the NOL index measurements, compared to control participants. Dysautonomia may explain the persistent symptoms observed in long COVID-19 patients, such as fatigue and hypoxia.
Authors In-Kyung Jeong, Kun Ho Yoon, Moon Kyu Lee
Abstract The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.
Authors Amanda B. Payne, Zunera Gilani, Shana Godfred-Cato, Ermias D. Belay, Leora R. Feldstein, Manish M. Patel, Adrienne G. Randolph, Margaret Newhams, Deepam Thomas, Reed Magleby, Katherine Hsu, Meagan MPH; Elizabeth Dufort, Angie Maxted, Michael Pietrowski, Allison Longenberger, Sally Bidol, Justin Henderson, Lynn Sosa, Alexandra Edmundson, Melissa Tobin-D’Angelo, Laura Edison, Sabrina Heidemann, Aalok R. Singh, John S. Giuliano Jr, Lawrence C. Kleinman, Keiko M. Tarquinio, Rowan F. Walsh, Julie C. Fitzgerald, Katharine N. Clouser, Shira J. Gertz, Ryan W. Carroll, Christopher L. Carroll, Brooke E. Hoots, Carrie Reed, F. Scott Dahlgren, Matthew E. Oster, Timmy J. Pierce, Aaron T. Curns, Gayle E. Langley, Angela P. Campbell
Abstract Importance Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. Objective To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. Design, Setting, and Participants This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. Exposures Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). Main Outcomes and Measures Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. Results In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). Conclusions and Relevance In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.
Authors Matthew D. Solomon, Mai Nguyen-Huynh, Thomas K. Leong, Janet Alexander, Jamal S. Rana, Jeffrey Klingman, Alan S. Go
Authors Tahmina Nasserie, Michael Hittle, Steven N. Goodman
Abstract Importance Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy. Objective To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection. Evidence Review A search of PubMed and Web of Science was conducted to identify studies published from January 1, 2020, to March 11, 2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19, SARS-CoV-2, coronavirus, 2019-nCoV, long-term, after recovery, long-haul, persistent, outcome, symptom, follow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study quality. Findings A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range [IQR], 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity. Conclusions and Relevance This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. Current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.
ANNALS OF INTERNAL MEDICINE
Authors Olivier Marion, Arnaud Del Bello, Florence Abravanel, Chloé Couat, Stanislas Faguer, Laure Esposito, Anne Laure Hebral, Jacques Izopet, Nassim Kamar
Authors Marie-Pierre Dubé, Audrey Lemaçon, Amina Barhdadi, Louis-Philippe Lemieux Perreault, Essaïd Oussaïd, Géraldine Asselin, Sylvie Provost, Maxine Sun, Johanna Sandoval, Marc-André Legault, Ian Mongrain, Anick Dubois, Diane Valois, Emma Dedelis, Jennifer Lousky, Julie Choi, Elisabeth Goulet, Christiane Savard, Lea-Mei Chicoine, Mariève Cossette, Malorie Chabot-Blanchet, Marie-Claude Guertin, Simon de Denus, Nadia Bouabdallaoui, Richard Marchand, Zohar Bassevitch, Anna Nozza, Daniel Gaudet, Philippe L. L’Allier, Julie Hussin, Guy Boivin, David Busseuil, Jean-Claude Tardif
Abstract We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10–8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10–8) in interaction with colchicine (P = 1.19 × 10–5) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.
Authors Sarah E Daugherty, Yinglong Guo, Kevin Heath, Micah C Dasmariñas, Karol Giuseppe Jubilo, Jirapat Samranvedhya, Marc Lipsitch, Ken Cohen
Abstract Objective To evaluate the excess risk and relative hazards for developing incident clinical sequelae after the acute phase of SARS-CoV-2 infection in adults aged 18-65. Design Retrospective cohort study. Setting Three merged data sources from a large United States health plan: a large national administrative claims database, an outpatient laboratory testing database, and an inpatient hospital admissions database. Participants Individuals aged 18-65 with continuous enrollment in the health plan from January 2019 to the date of a diagnosis of SARS-CoV-2 infection. Three comparator groups, matched by propensity score, to individuals infected with SARS-CoV-2: a 2020 comparator group, an historical 2019 comparator group, and an historical comparator group with viral lower respiratory tract illness. Main outcome measures More than 50 clinical sequelae after the acute phase of SARS-CoV-2 infection (defined as the date of first SARS-CoV-2 diagnosis (index date) plus 21 days) were identified using ICD-10 (international classification of diseases, 10th revision) codes. Excess risk in the four months after acute infection and hazard ratios with Bonferroni corrected 95% confidence intervals were calculated. Results 14% of adults aged ≤65 who were infected with SARS-CoV-2 (27 074 of 193 113) had at least one new type of clinical sequelae that required medical care after the acute phase of the illness, which was 4.95% higher than in the 2020 comparator group. The risk for specific new sequelae attributable to SARS-Cov-2 infection after the acute phase, including chronic respiratory failure, cardiac arrythmia, hypercoagulability, encephalopathy, peripheral neuropathy, amnesia (memory difficulty), diabetes, liver test abnormalities, myocarditis, anxiety, and fatigue, was significantly greater than in the three comparator groups (2020, 2019, and viral lower respiratory tract illness groups) (all P<0.001). Significant risk differences because of SARS-CoV-2 infection ranged from 0.02 to 2.26 per 100 people (all P<0.001), and hazard ratios ranged from 1.24 to 25.65 compared with the 2020 comparator group. Conclusions The results indicate the excess risk of developing new clinical sequelae after the acute phase of SARS-CoV-2 infection, including specific types of sequelae less commonly seen in other viral illnesses. Although individuals who were older, had pre-existing conditions, and were admitted to hospital because of covid-19 were at greatest excess risk, younger adults (aged ≤50), those with no pre-existing conditions, or those not admitted to hospital for covid-19 also had an increased risk of developing new clinical sequelae. The greater risk for incident sequelae after the acute phase of SARS-CoV-2 infection is relevant for healthcare planning.
Authors Lixue Huang, Bin Cao
SPRINGER LINK
Authors Arcelia Guerson-Gil, Leonidas Palaiodimos, Andrei Assa, Dimitris Karamanis, Damianos Kokkinidis, Natalia Chamorro-Pareja, Preeti Kishore, Jason M. Leider, Lawrence J. Brandt
Abstract It has been demonstrated that obesity is an independent risk factor for worse outcomes in patients with COVID-19. Our objectives were to investigate which classes of obesity are associated with higher in-hospital mortality and to assess the association between obesity and systemic inflammation. This was a retrospective study which included consecutive hospitalized patients with COVID-19 in a tertiary center. Three thousand five hundred thirty patients were included in this analysis (female sex: 1579, median age: 65 years). The median body mass index (BMI) was 28.8 kg/m2. In the overall cohort, a J-shaped association between BMI and in-hospital mortality was depicted. In the subgroup of men, BMI 35–39.9 kg/m2 and BMI ≥40 kg/m2 were found to have significant association with higher in-hospital mortality, while only BMI ≥40 kg/m2 was found significant in the subgroup of women. No significant association between BMI and IL-6 was noted. Obesity classes II and III in men and obesity class III in women were independently associated with higher in-hospital mortality in patients with COVID-19. The male population with severe obesity was the one that mainly drove this association. No significant association between BMI and IL-6 was noted.
Authors Chirag Patel, Farukh Ikram, Nicholas Nguyen, Hao Nguyen, Chijioke Ukoha, Lawrence Hoang, Priyanka Acharya, Manavjot Sidhu
Authors Justin D. Salciccioli, Lilin She, Abigail Tulchinsky, Frank Rockhold, Juan Carlos Cardet, Elliot Israel
Authors Marcio José Concepción Zavaleta, Julia Cristina Coronado Arroyo, Francisca Elena Zavaleta Gutiérrez,Luis Alberto Concepción Urteaga
Authors Cynthia Putri, Timotius Ivan Hariyanto, Joshua Edward Hananto, Kevin Christian, Rocksy Fransisca V. Situmeang, Andree Kurniawan
Abstract Background Parkinson's Disease (PD) is among one of the common comorbidities in older patients. People with PD may be more vulnerable to severe pneumonia, due to the impairment of pulmonary function. Currently, the association between PD and COVID-19 is not yet established. This study aims to analyze the relationship between PD and in-hospital outcomes of COVID-19. Materials and methods We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 25th, 2020. All articles published on COVID-19 and Parkinson's Disease were retrieved. The quality of the study was assessed using the Newcastle Ottawa Scale (NOS) tool for observational studies and Joanna Briggs Institute (JBI) Critical Appraisal Tools for cross-sectional studies. Statistical analysis was done using Review Manager 5.4 software. Results A total of 12 studies with 103,874 COVID-19 patients were included in this meta-analysis. This meta-analysis showed that Parkinson's Disease was associated with poor in-hospital outcomes [[OR 2.64 (95% CI 1.75–3.99), p < 0.00001, I2 = 81%] and its subgroup which comprised of severe COVID-19 [OR 2.61 (95% CI 1.98–3.43), p < 0.00001, I2 = 0%] and mortality from COVID-19 [RR 2.63 (95% CI 1.50–4.60), p = 0.0007, I2 = 91%]. Meta-regression showed that the association was influenced by age (p = 0.05), but not by gender (p = 0.46) and dementia (p = 0.23). Conclusions Extra care and close monitoring should be provided to Parkinson's Disease patients to minimize the risk of infections, preventing the development of severe and mortality outcomes.
Authors Maryann Mason, Ponni Arukumar, Joe Feinglass
PNAS
Authors Xiaoyue Ni, Wei Ouyang, Hyoyoung Jeong, Jin-Tae Kim, Andreas Tzaveils, Ali Mirzazadeh, Changsheng Wu, Jong Yoon Lee, Matthew Keller, Chaithanya K. Mummidisetty, Manish Patel, Nicholas Shawen, Joy Huang, Hope Chen, Sowmya Ravi, Jan-Kai Chang, KunHyuck Lee, Yixin Wu, Ferrona Lie, Youn J. Kang, Jong Uk Kim, Leonardo P. Chamorro, Anthony R. Banks, Ankit Bharat, Arun Jayaraman, Shuai Xu, John A. Rogers
Abstract Capabilities in continuous monitoring of key physiological parameters of disease have never been more important than in the context of the global COVID-19 pandemic. Soft, skin-mounted electronics that incorporate high-bandwidth, miniaturized motion sensors enable digital, wireless measurements of mechanoacoustic (MA) signatures of both core vital signs (heart rate, respiratory rate, and temperature) and underexplored biomarkers (coughing count) with high fidelity and immunity to ambient noises. This paper summarizes an effort that integrates such MA sensors with a cloud data infrastructure and a set of analytics approaches based on digital filtering and convolutional neural networks for monitoring of COVID-19 infections in sick and healthy individuals in the hospital and the home. Unique features are in quantitative measurements of coughing and other vocal events, as indicators of both disease and infectiousness. Systematic imaging studies demonstrate correlations between the time and intensity of coughing, speaking, and laughing and the total droplet production, as an approximate indicator of the probability for disease spread. The sensors, deployed on COVID-19 patients along with healthy controls in both inpatient and home settings, record coughing frequency and intensity continuously, along with a collection of other biometrics. The results indicate a decaying trend of coughing frequency and intensity through the course of disease recovery, but with wide variations across patient populations. The methodology creates opportunities to study patterns in biometrics across individuals and among different demographic groups.
AJNR (AMERICAN JOURNAL OF NEURORADIOLOGY)
Authors F. Al-Mufti, K. Amuluru, R. Sahni, K. Bekelis, R. Karimi, J. Ogulnick, J. Cooper, P. Overby, R. Nuoman, A. Tiwari, K. Berekashvili, N. Dangayach, J. Liang, G. Gupta, P. Khandelwal, J.F. Dominguez, T. Sursal, H. Kamal, K. Dakay, B. Taylor, E. Gulko, M. El-Ghanem, S.A. Mayer and C. Gandhi
Abstract BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is associated with hypercoagulability. We sought to evaluate the demographic and clinical characteristics of cerebral venous thrombosis among patients hospitalized for coronavirus disease 2019 (COVID-19) at 6 tertiary care centers in the New York City metropolitan area. MATERIALS AND METHODS: We conducted a retrospective multicenter cohort study of 13,500 consecutive patients with COVID-19 who were hospitalized between March 1 and May 30, 2020. RESULTS: Of 13,500 patients with COVID-19, twelve had imaging-proved cerebral venous thrombosis with an incidence of 8.8 per 10,000 during 3 months, which is considerably higher than the reported incidence of cerebral venous thrombosis in the general population of 5 per million annually. There was a male preponderance (8 men, 4 women) and an average age of 49 years (95% CI, 36–62 years; range, 17–95 years). Only 1 patient (8%) had a history of thromboembolic disease. Neurologic symptoms secondary to cerebral venous thrombosis occurred within 24 hours of the onset of the respiratory and constitutional symptoms in 58% of cases, and 75% had venous infarction, hemorrhage, or both on brain imaging. Management consisted of anticoagulation, endovascular thrombectomy, and surgical hematoma evacuation. The mortality rate was 25%. CONCLUSIONS: Early evidence suggests a higher-than-expected frequency of cerebral venous thrombosis among patients hospitalized for COVID-19. Cerebral venous thrombosis should be included in the differential diagnosis of neurologic syndromes associated with SARS-CoV-2 infection.
AHA JOURNALS
Authors Mina K. Chung, David A. Zidar, Michael R. Bristow, Scott J. Cameron, Timothy Chan, Clifford V. Harding III, Deborah H. Kwon, Tamanna Singh, John C. Tilton, Emily J. Tsai, Nathan R. Tucker, John Barnard, Joseph Loscalzo
Abstract A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.
HEALTH EUROPA
Authors HEALTH EUROPA
Authors Mark S Graham, Carole H Sudre, Anna May, Michela Antonelli, Benjamin Murray, Thomas Varsavsky, Kerstin Kläser, Liane S Canas, Erika Molteni, Marc Modat, David A Drew, Long H Nguyen, Lorenzo Polidori, Somesh Selvachandran, Christina Hu, Joan Capdevila, COVID-19 Genomics UK (COG-UK) Consortium, Alexander Hammers, Andrew T Chan, Jonathan Wolf, Tim D Spector, Claire J Steves, Sebastien Ourselin
JAC-ANTIMICROBIAL RESISTANCE (OXFORD ACADEMY)
Authors Shamshul Ansari, John P Hays, Andrew Kemp, Raymond Okechukwu, Jayaseelan Murugaiyan, Mutshiene Deogratias Ekwanzala, Maria Josefina Ruiz Alvarez, Maneesh Paul-Satyaseela, Chidozie Declan Iwu, Clara Balleste-Delpierre, Ed Septimus, Lawrence Mugisha, Joseph Fadare, Susmita Chaudhuri, Vindana Chibabhai, J M Rohini W W Wadanamby, Ziad Daoud, Yonghong Xiao, Thulasiraman Parkunan, Yara Khalaf, Nkuchia M M’Ikanatha, Maarten B M van Dongen
Abstract The COVID-19 pandemic presents a serious public health challenge in all countries. However, repercussions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on future global health are still being investigated, including the pandemic’s potential effect on the emergence and spread of global antimicrobial resistance (AMR). Critically ill COVID-19 patients may develop severe complications, which may predispose patients to infection with nosocomial bacterial and/or fungal pathogens, requiring the extensive use of antibiotics. However, antibiotics may also be inappropriately used in milder cases of COVID-19 infection. Further, concerns such as increased biocide use, antimicrobial stewardship/infection control, AMR awareness, the need for diagnostics (including rapid and point-of-care diagnostics) and the usefulness of vaccination could all be components shaping the influence of the COVID-19 pandemic. In this publication, the authors present a brief overview of the COVID-19 pandemic and associated issues that could influence the pandemic’s effect on global AMR.
JOURNAL OF HEPATOLOGY
Authors Markus Cornberg, Maria Buti, Christiane S. Eberhardt, Paolo Antonio Grossi, Daniel Shouval
Authors Paul Aveyard, Min Gao, Nicola Lindson, Jamie Hartmann-Boyce, Peter Watkinson, Duncan Young, Carol A C Coupland, Pui San Tan, Ashley K Clift, David Harrison, Doug W Gould, Ian D Pavord, Julia Hippisley-Cox
Authors Baptiste Queré, Alain Saraux, Thierry Marhadour, Sandrine Jousse-Joulin, Divi Cornecc, Camille Houssais, Guillermo Carvajal Alegriac, Maxime Quiviger, Margot Le Guillou, Valérie Devauchelle-Pensec, Dewi Guellec
Authors Maura Boldrini, Peter D. Canoll, Robyn S. Klein
Authors Ingrid Torjesen
OXFORD ACADEMY
Authors John W Baddley
Authors Ani Nalbandian, Kartik Sehgal, Aakriti Gupta, Mahesh V. Madhavan, Claire McGroder, Jacob S. Stevens, Joshua R. Cook, Anna S. Nordvig, Daniel Shalev, Tejasav S. Sehrawat, Neha Ahluwalia, Behnood Bikdeli, Donald Dietz, Caroline Der-Nigoghossian, Nadia Liyanage-Don, Gregg F. Rosner, Elana J. Bernstein, Sumit Mohan, Akinpelumi A. Beckley, David S. Seres, Toni K. Choueiri, Nir Uriel, John C. Ausiello, Domenico Accili, Daniel E. Freedberg, Matthew Baldwin, Allan Schwartz, Daniel Brodie, Christine Kim Garcia, Mitchell S. V. Elkind, Jean M. Connors, John P. Bilezikian, Donald W. Landry, Elaine Y. Wan
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.
Authors Samantha J. Rivard, C. Ann Vitous, Shelytia Cocroft, Christopher Varlamos, Ashley Duby, Pasithorn A. Suwanabol, Scott E. Regenbogen, Lillias H. Maguire, Gifty Kwaky
Abstract Background To focus on critical care needs of coronavirus patients, elective operations were postponed and selectively rescheduled. The effect of these measures on patients was unknown. We sought to understand patients’ perspectives regarding surgical care during the CoVID-19 pandemic to improve future responses. Methods We performed qualitative interviews with patients whose operations were postponed. Interviews explored patient responses to: 1) surgery postponement; 2) experience of surgery; 3) impacts of rescheduling/postponement on emotional/physical health; 4) identifying areas of improvement. Interviews were recorded, transcribed, coded, and analyzed through an integrated approach. Results Patient perspectives fell within the following domains: 1) reactions to surgery postponement/rescheduling; 2) experience of surgery during CoVID-19 pandemic; 3) reflections on communication; 4) patient trust in surgeons and healthcare. Conclusions We found no patient-reported barriers to rescheduling surgery. Several areas of care which could be improved (communication). There was an unexpected sense of trust in surgeons and the hospital.
BIORXIV
Authors Luca Ferasin, Matthieu Fritz, Heidi Ferasin, Pierre Becquart, Vincent Legros, Eric M. Leroy
Abstract Domestic pets can contract SARS-CoV-2 infection but, based on the limited information available to date, it is unknown whether the new British B.1.1.7 variant can more easily infect certain animal species or increase the possibility of human-to-animal transmission. In this study, we report the first cases of infection of domestic cats and dogs by the British B.1.1.7 variant of SARS-CoV-2 diagnosed at a specialist veterinary hospital in the South-East of England. Furthermore, we discovered that many owners and handlers of these pets had developed Covid-19 respiratory symptoms 3-6 weeks before their pets became ill and had also tested PCR positive for Covid-19. Interestingly, all these B.1.1.7 infected pets developed atypical clinical manifestations, including severe cardiac abnormalities secondary to myocarditis and a profound impairment of the general health status of the patient but without any primary respiratory signs. Together, our findings demonstrate for the first time the ability for companion animals to be infected by the B.1.1.7 variant of SARS-CoV-2 and raise questions regarding its pathogenicity in these animals. Moreover, given the enhanced infectivity and transmissibility of B.1.1.7 variant for humans, these findings also highlights more than ever the risk that companion animals may potentially play a significant role in SARS-CoV-2 outbreak dynamics than previously appreciated.
Authors The Writing Committee for the COMEBAC Study Group
Abstract Importance Little is known about long-term sequelae of COVID-19. Objective To describe the consequences at 4 months in patients hospitalized for COVID-19. Design, Setting, and Participants In a prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit. Exposures Survival of hospitalization for COVID-19. Main Outcomes and Measures Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography. Results Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years [SD, 16 years]; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 [best] to 5 [worst]). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale “role limited owing to physical problems” (possible range, 0 [best] to 100 [worst]). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%). Conclusions and Relevance Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.
Authors Mayara Bearse, Yin P. Hung, Aram J. Krauson, Liana Bonanno, Baris Boyraz, Cynthia K. Harris, T. Leif Helland, Caroline F. Hilburn, Bailey Hutchison, Soma Jobbagy, Michael S. Marshall, Daniel J. Shepherd, Julian A. Villalba, Isabela Delfino, Javier Mendez-Pena, Ivan Chebib, Christopher Newton-Cheh, James R. Stone
Abstract COVID-19 has been associated with cardiac injury and dysfunction. While both myocardial inflammatory cell infiltration and myocarditis with myocyte injury have been reported in patients with fatal COVID-19, clinical–pathologic correlations remain limited. The objective was to determine the relationships between cardiac pathological changes in patients dying from COVID-19 and cardiac infection by SARS-CoV-2, laboratory measurements, clinical features, and treatments. In a retrospective study, 41 consecutive autopsies of patients with fatal COVID-19 were analyzed for the associations between cardiac inflammation, myocarditis, cardiac infection by SARS-CoV-2, clinical features, laboratory measurements, and treatments. Cardiac infection was assessed by in situ hybridization and NanoString transcriptomic profiling. Cardiac infection by SARS-CoV-2 was present in 30/41 cases: virus+ with myocarditis (n = 4), virus+ without myocarditis (n = 26), and virus– without myocarditis (n = 11). In the cases with cardiac infection, SARS-CoV-2+ cells in the myocardium were rare, with a median density of 1 cell/cm2. Virus+ cases showed higher densities of myocardial CD68+ macrophages and CD3+ lymphocytes, as well as more electrocardiographic changes (23/27 vs 4/10; P = 0.01). Myocarditis was more prevalent with IL-6 blockade than with nonbiologic immunosuppression, primarily glucocorticoids (2/3 vs 0/14; P = 0.02). Overall, SARS-CoV-2 cardiac infection was less prevalent in patients treated with nonbiologic immunosuppression (7/14 vs 21/24; P = 0.02). Myocardial macrophage and lymphocyte densities overall were positively correlated with the duration of symptoms but not with underlying comorbidities. In summary, cardiac infection with SARS-CoV-2 is common among patients dying from COVID-19 but often with only rare infected cells. Cardiac infection by SARS-CoV-2 is associated with more cardiac inflammation and electrocardiographic changes. Nonbiologic immunosuppression is associated with lower incidences of myocarditis and cardiac infection by SARS-CoV-2.
Authors Virginie Lambrecq, Aurélie Hanin, Esteban Munoz-Musat, Lydia Chougar, Salimata Gassama, Cécile Delorme, Louis Cousyn, Alaina Borden, Maria Damiano, Valerio Frazzini, Gilles Huberfeld, Frank Landgraf, Vi-Huong Nguyen-Michel, Phintip Pichit, Aude Sangare, Mario Chavez, Capucine Morélot-Panzini, Elise Morawiec, Mathieu Raux, Charles-Edouard Luyt, Pierre Rufat, Damien Galanaud, Jean-Christophe Corvol, Catherine Lubetzki, Benjamin Rohaut, Sophie Demeret, Nadya Pyatigorskaya, Lionel Naccache, Vincent Navarro
Abstract Importance There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19–related encephalopathy and guide clinical management. Objectives To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19–related encephalopathy. Design, Setting, and Participants This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020. Exposures Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription–polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest. Main Outcomes and Measures Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records. Results Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter–enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19–related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter–enhancing lesions. Conclusions and Relevance The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19–related encephalopathy and guide treatment strategy.
WORLD OBESITY
Authors WORLD OBESITY
Authors Nitipong Permpalung, Teresa Po-Yu Chiang, Allan B Massie, Sean X Zhang, Robin K Avery, Saman Nematollahi, Darin Ostrander, Dorry L Segev, Kieren A Marr
Abstract Background COVID-19 associated pulmonary aspergillosis (CAPA) occurs in critically ill COVID-19 patients. Risks and outcomes remain poorly understood. Methods A retrospective cohort study of adult mechanically ventilated COVID-19 patients admitted to five Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores. Results Amongst the cohort of 396 people, 39 met criteria for CAPA. Compared to those without, patients with CAPA were more likely to have underlying pulmonary vascular disease (41% vs 21.6%, p=0.01), liver disease (35.9% vs 18.2%, p=0.02), coagulopathy (51.3% vs 33.1%, p=0.03), solid tumors (25.6% vs 10.9%, p=0.017), multiple myeloma (5.1% vs 0.3%, p=0.027), corticosteroid exposure during index admission (66.7% vs 42.6%, p=0.005), and had a lower BMI (median 26.6 vs 29.9, p=0.04). People with CAPA had worse outcomes as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio 1.081.091.1, p<0.001), and advancing in severity almost twice as fast (subhazard ratio, sHR 1.31.82.5, p<0.001). People with CAPA were intubated twice as long as those without (sHR) 0.40.50.6, p<0.001) and had a longer hospital length of stay [median (IQR) 41.1 (20.5, 72.4) vs 18.5 (10.7, 31.8), p<0.001]. Conclusion CAPA is associated with poor outcomes. Attention towards preventative measures (screening and/or prophylaxis) is warranted in people with high risk of developing CAPA.
Authors John N Aucott, Alison W Rebman
Authors Matthew W. Martinez, Andrew M. Tucker, O. Josh Bloom, Gary Green, John P. DiFiori, Gary Solomon, Dermot Phelan, Jonathan H. Kim, Willem Meeuwisse, Allen K. Sills, Dana Rowe, Isaac I. Bogoch, Paul T. Smith, Aaron L. Baggish, Margot Putukian, David J. Engel
Abstract Importance The major North American professional sports leagues were among the first to return to full-scale sport activity during the coronavirus disease 2019 (COVID-19) pandemic. Given the unknown incidence of adverse cardiac sequelae after COVID-19 infection in athletes, these leagues implemented a conservative return-to-play (RTP) cardiac testing program aligned with American College of Cardiology recommendations for all athletes testing positive for COVID-19. Objective To assess the prevalence of detectable inflammatory heart disease in professional athletes with prior COVID-19 infection, using current RTP screening recommendations. Design, Setting, and Participants This cross-sectional study reviewed RTP cardiac testing performed between May and October 2020 on professional athletes who had tested positive for COVID-19. The professional sports leagues (Major League Soccer, Major League Baseball, National Hockey League, National Football League, and the men’s and women’s National Basketball Association) implemented mandatory cardiac screening requirements for all players who had tested positive for COVID-19 prior to resumption of team-organized sports activities. Exposures Troponin testing, electrocardiography (ECG), and resting echocardiography were performed after a positive COVID-19 test result. Interleague, deidentified cardiac data were pooled for collective analysis. Those with abnormal screening test results were referred for additional testing, including cardiac magnetic resonance imaging and/or stress echocardiography. Main Outcomes and Measures The prevalence of abnormal RTP test results potentially representing COVID-19–associated cardiac injury, and results and outcomes of additional testing generated by the initial screening process. Results The study included 789 professional athletes (mean [SD] age, 25 [3] years; 777 men [98.5%]). A total of 460 athletes (58.3%) had prior symptomatic COVID-19 illness, and 329 (41.7%) were asymptomatic or paucisymptomatic (minimally symptomatic). Testing was performed a mean (SD) of 19 (17) days (range, 3-156 days) after a positive test result. Abnormal screening results were identified in 30 athletes (3.8%; troponin, 6 athletes [0.8%]; ECG, 10 athletes [1.3%]; echocardiography, 20 athletes [2.5%]), necessitating additional testing; 5 athletes (0.6%) ultimately had cardiac magnetic resonance imaging findings suggesting inflammatory heart disease (myocarditis, 3; pericarditis, 2) that resulted in restriction from play. No adverse cardiac events occurred in athletes who underwent cardiac screening and resumed professional sport participation. Conclusions and Relevance This study provides large-scale data assessing the prevalence of relevant COVID-19–associated cardiac pathology with implementation of current RTP screening recommendations. While long-term follow-up is ongoing, few cases of inflammatory heart disease have been detected, and a safe return to professional sports activity has thus far been achieved.
JAAD INTERNATIONAL
Authors See Wei Tan, Yew Chong Tam, Choon Chiat Oh
Authors Gianluca Campo, Daniela Fortuna, Elena Berti, Rossana De Palma, Giuseppe Di Pasquale, Marcello Galvani, Alessandro Navazio, Giancarlo Piovaccari, Andrea Rubboli, Gabriele Guardigli, Nazzareno Galiè, Giuseppe Boriani, Stefano Tondi, Diego Ardissino, Massimo Piepoli, Federico Banchelli, Andrea Santarelli, Gianni Casella
Abstract Background The COVID-19 pandemic has put several healthcare systems under severe pressure. The present analysis investigates how the first wave of the COVID-19 pandemic affected the myocardial infarction (MI) network of Emilia-Romagna (Italy). Methods Based on Emilia-Romagna mortality registry and administrative data from all the hospitals from January 2017 to June 2020, we analysed: i) temporal trend in MI hospital admissions; ii) characteristics, management, and 30-day mortality of MI patients; iii) out-of-hospital mortality for cardiac cause. • View related content for this article Findings Admissions for MI declined on February 22, 2020 (IRR -19.5%, 95%CI from -8.4% to -29.3%, p = 0.001), and further on March 5, 2020 (IRR -21.6%, 95%CI from -9.0% to -32.5%, p = 0.001). The return to pre-COVID-19 MI-related admission levels was observed from May 13, 2020 (IRR 34.3%, 95%CI 20.0%-50.2%, p<0.001). As compared to those before the pandemic, MI patients admitted during and after the first wave were younger and with fewer risk factors. The 30-day mortality remained in line with that expected based on previous years (ratio observed/expected was 0.96, 95%CI 0.84–1.08). MI patients positive for SARS-CoV-2 were few (1.5%) but showed poor prognosis (around 5-fold increase in 30-day mortality). In 2020, the number of out-of-hospital cardiac deaths was significantly higher (ratio observed/expected 1.17, 95%CI 1.08–1.27). The peak was reached in April. Interpretation In Emilia-Romagna, MI hospitalizations significantly decreased during the first wave of the COVID-19 pandemic. Management and outcomes of hospitalized MI patients remained unchanged, except for those with SARS-CoV-2 infection. A concomitant increase in the out-of-hospital cardiac mortality was observed.
Authors Thomas H Brix, Laszlo Hegedüs, Jesper Hallas, Lars C Lund
Authors Jennifer K. Logue, Nicholas M. Franko, Denise J. McCulloch, Dylan McDonald, Ariana Magedson, Caitlin R. Wolf, Helen Y. Chu
Authors Retesh Bajaj, Hannah C Sinclair, Kush Patel, Ben Low, Ana Pericao, Charlotte Manisty, Oliver Guttmann, Filip Zemrak, Owen Miller, Paula Longhi, Alastair Proudfoot, Boris Lams, Sangita Agarwal, Federica M Marelli-Berg, Simon Tiberi, Teresa Cutino-Moguel, Gerry Carr-White, Saidi A Mohiddin
Authors Santhoshini Leela Ramani, Jonathan Samet, Colin K. Franz, Christine Hsieh, Cuong V. Nguyen, Craig Horbinski, Swati Deshmukh
Abstract The global pandemic of coronavirus disease 2019 (COVID-19) has revealed a surprising number of extra-pulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While myalgia is a common clinical feature of COVID-19, other musculoskeletal manifestations of COVID-19 were infrequently described early during the pandemic. There have been emerging reports, however, of an array of neuromuscular and rheumatologic complications related to COVID-19 infection and disease course including myositis, neuropathy, arthropathy, and soft tissue abnormalities. Multimodality imaging supports diagnosis and evaluation of musculoskeletal disorders in COVID-19 patients. This article aims to provide a first comprehensive summary of musculoskeletal manifestations of COVID-19 with review of imaging.
Authors E. Murillo-Zamora, O. Mendoza-Cano, I. Delgado-Enciso, C.M. Hernandez-Suarez
Abstract Objective The aim of the study was to evaluate factors predicting severe symptomatic laboratory-confirmed (via Reverse transcription polymerase chain reaction, RT-PCR polymerase chain reaction) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. Study design This is a nationwide retrospective cohort study that was conducted in Mexico. Methods Data from 258 reinfection cases (at least 28 days between both episodes onset) were analyzed. We used risk ratios (RRs) and 95% confidence intervals (CIs) to evaluate predictors of severe (dyspnea requiring hospital admission) secondary SARS-CoV-2 infection. Results The risk of severe disease was 14.7%, and the observed overall fatality rate was 4.3%. Patients with more serious primary disease were more likely to develop severe symptoms (39.5% vs. 5.5%, P < 0.001) during reinfection. In multiple analysis, factors associated with an increased risk of severe symptomatic SARS-CoV-2 reinfection were increasing age (RRper year = 1.007, 95% CI = 1.003–1.010), comorbidities (namely, obesity [RR = 1.12, 95% CI = 1.01–1.24], asthma [RR = 1.26, 95% CI = 1.06–1.50], type 2 diabetes mellitus [RR = 1.22, 95% CI = 1.07–1.38]), and previous severe laboratory-confirmed coronavirus disease 2019 (RR = 1.20, 95% CI = 1.03–1.39). Conclusions To the best of our knowledge, this is the first study evaluating disease outcomes in a large set of laboratory-positive cases of symptomatic SARS-CoV-2 reinfection, and factors associated with illness severity were characterized. Our results may contribute to the current knowledge of SARS-CoV-2 pathogenicity and to identify populations at increased risk of a poorer outcome after reinfection.
Authors David W. Nauen, Jody E. Hooper, C. Matthew Stewart, Isaac H. Solomon
Authors Noémie Zucman, Fabrice Uhel, Diane Descamps, Damien Roux, Jean-Damien Ricard
Authors Roos S G Sablerolles, Melvin Lafeber, Janneke A L van Kempen, Bob P A van de Loo, Eric Boersma, Wim J R Rietdijk, Harmke A Polinder-Bos, Simon P Mooijaart, Hugo van der Kuy, Jorie Versmissen, Miriam C Faes,
Authors The Lancet Haematology
AJOG (AMERICAN JOURNAL OF OBSTRETICS GYNECOLOGY)
Authors Maria Gomez-Roas, Ka’Derricka Davis, Karolina Leziak, Jenise Jackson, Brittney R. Williams, Joe M. Feinglass, William A. Grobman, Lynn M. Yee
Authors Min‐Chul Kim, Chunguang Cui, Kyeong‐Ryeol Shin, Joon‐Yong Bae, Oh‐Joo Kweon, Mi‐Kyung Lee, Seong‐Ho Choi, Sun‐Young Jung, Man‐Seong Park, Jin‐Won Chung
EJC (EUROPEAN JOURNAL OF CANCER)
Authors Liang En Wee, Edwin P. Conceicao, Kennedy Y.-Y. Ng, Chee K. Tham, Indumathi Venkatachalam
Authors Norbert Stefan, Andreas L. Birkenfeld, Matthias B. Schulze
Abstract Obesity and impaired metabolic health are established risk factors for the non-communicable diseases (NCDs) type 2 diabetes mellitus, cardiovascular disease, neurodegenerative diseases, cancer and nonalcoholic fatty liver disease, otherwise known as metabolic associated fatty liver disease (MAFLD). With the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), obesity and impaired metabolic health also emerged as important determinants of severe coronavirus disease 2019 (COVID-19). Furthermore, novel findings indicate that specifically visceral obesity and characteristics of impaired metabolic health such as hyperglycaemia, hypertension and subclinical inflammation are associated with a high risk of severe COVID-19. In this Review, we highlight how obesity and impaired metabolic health increase complications and mortality in COVID-19. We also summarize the consequences of SARS-CoV-2 infection for organ function and risk of NCDs. In addition, we discuss data indicating that the COVID-19 pandemic could have serious consequences for the obesity epidemic. As obesity and impaired metabolic health are both accelerators and consequences of severe COVID-19, and might adversely influence the efficacy of COVID-19 vaccines, we propose strategies for the prevention and treatment of obesity and impaired metabolic health on a clinical and population level, particularly while the COVID-19 pandemic is present.
Authors Karola S. Jering, Brian L. Claggett, Jonathan W. Cunningham, Ning Rosenthal, Orly Vardeny, Michael F. Greene, Scott D. Solomon
Authors Ziad Bakouny, Marco Paciotti, Andrew L. Schmidt, Stuart R. Lipsitz, Toni K. Choueiri, Quoc-Dien Trinh
Authors Priya Venkatesan
Authors Milena S. Marcolino, Patricia K. Ziegelmann, Maira V.R. Souza-Silva, I.J.B. Nascimento, Luana M. Oliveira, Luanna S. Monteiro, Thaís L.S. Sales, Karen B. Ruschel, Karina P.M.P. Martins, Ana Paula B.S. Etges, Israel Molinae, Carisi A. Polanczykb
Abstract Objectives To describe the clinical characteristics, laboratory results, imaging findings, and in-hospital outcomes of COVID-19 patients admitted to Brazilian hospitals. Methods A cohort study of laboratory-confirmed COVID-19 patients who were hospitalized from March 2020 to September 2020 in 25 hospitals. Data were collected from medical records using Research Electronic Data Capture (REDCap) tools. A multivariate Poisson regression model was used to assess the risk factors for in-hospital mortality. Results For a total of 2,054 patients (52.6% male; median age of 58 years), the in-hospital mortality was 22.0%; this rose to 47.6% for those treated in the intensive care unit (ICU). Hypertension (52.9%), diabetes (29.2%), and obesity (17.2%) were the most prevalent comorbidities. Overall, 32.5% required invasive mechanical ventilation, and 12.1% required kidney replacement therapy. Septic shock was observed in 15.0%, nosocomial infection in 13.1%, thromboembolism in 4.1%, and acute heart failure in 3.6%. Age >= 65 years, chronic kidney disease, hypertension, C-reactive protein ≥ 100 mg/dL, platelet count < 100 × 109/L, oxygen saturation < 90%, the need for supplemental oxygen, and invasive mechanical ventilation at admission were independently associated with a higher risk of in-hospital mortality. The overall use of antimicrobials was 87.9%. Conclusions This study reveals the characteristics and in-hospital outcomes of hospitalized patients with confirmed COVID-19 in Brazil. Certain easily assessed parameters at hospital admission were independently associated with a higher risk of death. The high frequency of antibiotic use points to an over-use of antimicrobials in COVID-19 patients.
Authors Serafino Buono, Marinella Zingale, Santina Citta, Vita Mongelli, Grazia Trubia, Giovanna Mascali, Paola Occhipinti, Enrica Pettinato, Raffaele Ferri, Catalda Gagliano, Donatella Greco
Abstract During the COVID-19 pandemic, the Oasi Research Institute of Troina (Italy) became an important hotbed for infection; in fact, 109 patients with different levels of Intellectual Disability (ID) tested positive for COVID-19. The procedures and interventions put in place at the Oasi Research Institute due to the COVID-19 pandemic are exhaustively reported in this paper. The description of the clinical procedures as well as remote/in person psychological support services provided to people with ID and their families are here divided into three different sections: Phase I (or Acute phase), Phase II (or Activity planning), and Phase III (or Activity consolidation). In each section, the main psycho-pathological characteristics of patients, the reactions of family members and the multidisciplinary interventions put in place are also described.
Authors Marlene S.Williams, Sammy Zakari, Michelle D'Alessandro, Susan Kraeuter, Heather Hicks
BMJ
Authors David Salman, Dane Vishnubala, Peter Le Feuvre, Thomas Beaney, Jonathan Korgaonkar, Azeem Majeed, Alison H McGregor
BMC PSYCHIATRY
Authors Maurizio Bonati, Rita Campi, Michele Zanetti, Massimo Cartabia, Francesca Scarpellini, Antonio Clavenna, Giulia Segre
Authors Brenda T Pun, Rafael Badenes, Gabriel Heras La Calle, Onur M Orun, Wencong Chen, Rameela Raman, Beata-Gabriela K Simpson, Stephanie Wilson-Linville, Borja Hinojal Olmedillo, Ana Vallejo de la Cueva, Mathieu van der Jagt, Rosalía Navarro Casado, Pilar Leal Sanz, Günseli Orhun, Carolina Ferrer Gómez, Karla Núñez Vázquez, Patricia Piñeiro Otero, Fabio Silvio Taccone, Elena Gallego Curto, Anselmo Caricato, Hilde Woien, Guillaume Lacave, Hollis R O’Neal Jr, Sarah J Peterson, Nathan E Brummel, Timothy D Girard, E Wesley Ely, Pratik P Pandharipande
Authors Chaolin Huang, Lixue Huang, Yeming Wang, Xia Li, Lili Ren, Xiaoying Gu, Liang Kang, Li Guo, Min Liu, Xing Zhou, Jianfeng Luo, Zhenghui Huang, Shengjin Tu, Yue Zhao, Li Chen, Decui Xu, Yanping Li, Caihong Li, Lu Peng, Yong Li , Wuxiang Xie, Dan Cui, Lianhan Shang, Guohui Fan, Jiuyang Xu, Geng Wang, Ying Wang, Jingchuan Zhong, Chen Wang , Jianwei Wang, Dingyu Zhang, Bin Cao
Authors TOM SOLOMON
MDPI
Authors Laura Magnasco, Malgorzata Mikulska, Daniele Roberto Giacobbe, Lucia Taramasso, Antonio Vena, Chiara Dentone, Silvia Dettori, Stefania Tutino, Laura Labate, Vincenzo Di Pilato, Francesca Crea, Erika Coppo, Giulia Codda, Chiara Robba, Lorenzo Ball, Nicolo’ Patroniti, Anna Marchese. Paolo Pelosi, Matteo Bassetti
Abstract The possible negative impact of severe adult respiratory distress caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19) on antimicrobial stewardship and infection control has been postulated, but few real-life data are available. The aim of this study was to report our experience with colonization/infection of carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Candida auris among critically ill COVID-19 patients admitted to the intensive care unit (ICU). All COVID-19 patients admitted to the ICUs at San Martino Policlinico Hospital–IRCCS in Genoa, Italy, were screened from 28 February to 31 May 2020. One-hundred and eighteen patients admitted to COVID-19 ICUs were included in the study. Among them, 12 (10.2%) became colonized/infected with CRPA, 6 (5.1%) with C. auris and 2 (1.6%) with CR-Kp. All patients with CRPA received prior treatment with meropenem, and in 11 (91.7%) infection was not preceded by colonization. Four patients (66.7%) developed C. auris candidemia. A significant spread of resistant pathogens was observed among critically ill COVID-19 patients. Dedicated strategies are warranted to prevent horizontal spread and maintain effective antimicrobial stewardship programs in the setting of COVID-19 care.
Authors Anahita Rouzé, Ignacio Martin-Loeches, Pedro Povoa, Demosthenes Makris, Antonio Artigas, Mathilde Bouchereau, Fabien Lambiotte, Matthieu Metzelard, Pierre Cuchet, Claire Boulle Geronimi, Marie Labruyere, Fabienne Tamion, Martine Nyunga, Charles-Edouard Luyt, Julien Labreuche, Olivier Pouly, Justine Bardin, Anastasia Saade, Pierre Asfar, Jean-Luc Baudel, Alexandra Beurton, Denis Garot, Iliana Ioannidou, Louis Kreitmann, Jean-François Llitjos, Eleni Magira, Bruno Mégarbane, David Meguerditchian, Edgar Moglia, Armand Mekontso-Dessap, Jean Reignier, Matthieu Turpin, Alexandre Pierre, Gaetan Plantefeve, Christophe Vinsonneau, Pierre-Edouard Floch, Nicolas Weiss, Adrian Ceccato, Antoni Torres, Alain Duhamel, Saad Nseir
Authors Sarah Fredrich Benjamin M Greenberg Kimmo J Hatanpaa
Authors Manlio Milanese, Angelo Guido Corsico, Salvatore Bellofiore, Laura Carrozzi, Fabiano Di Marco, Bruno Iovene, Luca Richeldi, Antonio Sanna, Pierachille Santus, Mario Schisano, Nicola Scichilone, Carlo Vancheri, Isa Cerveri
Abstract The 2019 coronavirus disease (COVID-19) pandemic is currently a challenge worldwide. Due to the characteristics of lung function tests, the risk of cross infection may be high between health care workers and patients. The role of lung function testing is well defined for the diagnosis of various diseases and conditions. Lung function tests are also indispensable in evaluating the response to medical treatment, in monitoring patient respiratory and systemic pathologies, and in evaluating preoperative risk in cardiothoracic and major abdominal surgeries. However, lung function testing represents a potential route for COVID-19 transmission, due to the aerosol generated during the procedures and the concentration of patients with pulmonary diseases in lung function laboratories. Currently, the opportunities for COVID-19 transmission remain partially unknown, and data are continuously evolving. This review provides useful information on the risks and recommendations for lung function testing, which have varied according to the phase of the pandemic. This information may support national and regional boards and the health authorities to which they belong. There is a need for rapid re-opening of lung function laboratories, but maximum safety is required in the COVID-19 era.
WILEY ONLINE LIBRARY
Authors Christian Hoffmann José L. Casado Georg Härter Pilar Vizcarra Ana Moreno Dario Cattaneo Paola Meraviglia Christoph D. Spinner Farhad Schabaz Stephan Grunwald Cristina Gervasoni
Abstract Objectives A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID‐19 pandemic. Clinical data on patients co‐infected with HIV and SARS‐CoV‐2 are still scarce. Methods This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID‐19 in people living with HIV (PLWH), infected with SARS‐CoV‐2 in three countries in different clinical settings. COVID‐19 was clinically classified as to be mild‐to‐moderate or severe. Results Of 175 patients, 49 (28%) had severe COVID‐19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID‐19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID‐19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS‐defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID‐19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26‐6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir. Conclusions In PLWH, immune deficiency is a possible risk factor for severe COVID‐19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.
Authors Eskild Petersen
Authors Lionel Piroth, Jonathan Cottenet, Anne-Sophie Mariet, Philippe Bonniaud, Mathieu Blot, Pascale Tubert-Bitter, Catherine Quantin
Authors Raymond Pranata, Joshua Henrina, Michael Anthonius Lim, Sherly Lawrensia, Emir Yonas, Rachel Vania, Ian Huang, Antonia Anna Lukito, Ketut Suastika, R. A. Tuty Kuswardhani, Siti Setiati
Introduction: National Institute for Health and Care Excellence (NICE) endorsed clinical frailty scale (CFS) to help with decision-making. However, this recommendation lacks an evidence basis and is controversial. This meta- analysis aims to quantify the dose-response relationship between CFS and mortality in COVID-19 patients, with a goal of supplementing the evidence of its use. Methods: We performed a systematic literature search from several electronic databases up until 8 September 2020. We searched for studies investigating COVID-19 patients and reported both (1) CFS and its distribution (2) CFS and its association with mortality. The outcome of interest was mortality, defined as clinically validated death or non-survivor. The odds ratio (ORs) will be reported per 1% increase in CFS. The potential for a non- linear relationship based on ORs of each quantitative CFS was examined using restricted cubic splines with a three-knots model. Results: There were a total of 3817 patients from seven studies. Mean age was 80.3 (SD 8.2), and 53% (48–58%) were males. The pooled prevalence for CFS 1–3 was 34% (32–36%), CFS 4–6 was 42% (40–45%), and CFS 7–9 was 23% (21–25%). Each 1-point increase in CFS was associated with 12% increase in mortality (OR 1.12 (1.04, 1.20), p = 0.003; I 2 : 77.3%). The dose-response relationship was linear (Pnon-linearity=0.116). The funnel-plot analysis was asymmetrical; Trim-and-fill analysis by the imputation of two studies on the left side resulted in OR of 1.10 [1.03, 1.19]. Conclusion: This meta-analysis showed that increase in CFS was associated with increase in mortality in a linear fashion.
Authors John P. Donnelly, Xiao Qing Wang, Theodore J. Iwashyna, Hallie C. Prescott
Authors Stephen Keddie, Julia Pakpoor, Christina Mousele, Menelaos Pipis, Pedro M Machado, Mark Foster, Christopher J Record, Ryan Y S Keh, Janev Fehmi, Ross W Paterson, Viraj Bharambe, Lisa M Clayton, Claire Allen, Olivia Price, Jasmine Wall, Annamaria Kiss-Csenki, Dipa P Rathnasabapathi, Ruth Geraldes, Tatyana Yermakova, Joshua King-Robson, Maya Zosmer, Sanjeev Rajakulendran, Sheetal Sumaria, Simon F Farmer, Ross Nortley, Charles R Marshall, Edward J Newman, Niranjanan Nirmalananthan, Guru Kumar, Aswin A Pinto, James Holt, Tim M Lavin, Kathryn M Brennan, Michael S Zandi, Dipa L Jayaseelan, Jane Pritchard, Robert D M Hadden, Hadi Manji, Hugh J Willison, Simon Rinaldi, Aisling S Carr, Michael P Lunn
Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in his cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65–1.88 per 100 000 individuals per year. In 2020, GBS and COVID-19 incidences varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: −0.56 to 0.63, P = 0.86). GBS incidence fell between March and May 2020 compared to the same months of 2016–19. In an independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) likely related to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.
Authors Fabiana Fiasca, Mauro Minelli, Dominga Maio, Martina Minelli, Ilaria Vergallo, Stefano Necozione, Antonella Mattei
Abstract The COVID-19 outbreak disproportionately affected the elderly and areas with higher population density. Among the multiple factors possibly involved, a role for air pollution has also been hypothesized. This nationwide observational study demonstrated the significant positive relationship between COVID-19 incidence rates and PM2.5 and NO2 levels in Italy, both considering the period 2016–2020 and the months of the epidemic, through univariate regression models, after logarithmic transformation of the variables, as the data were not normally distributed. That relationship was confirmed by a multivariate analysis showing the combined effect of the two pollutants, adjusted for the old-age index and population density. An increase in PM2.5 and NO2 concentrations by one unit (1 µg/m3) corresponded to an increase in incidence rates of 1.56 and 1.24 × 104 people, respectively, taking into account the average levels of air pollutants in the period 2016–2020, and 2.79 and 1.24 × 104 people during March–May 2020. Considering the entire epidemic period (March–October 2020), these increases were 1.05 and 1.01 × 104 people, respectively, and could explain 59% of the variance in COVID-19 incidence rates (R2 = 0.59). This evidence could support the implementation of targeted responses by focusing on areas with low air quality to mitigate the spread of the disease.
Authors QuanQiu Wang, Nathan A. Berger, Rong Xu
Importance Patients with specific cancers may be at higher risk than those without cancer for coronavirus disease 2019 (COVID-19) and its severe outcomes. At present, limited data are available on the risk, racial disparity, and outcomes for COVID-19 illness in patients with cancer.
Objectives To investigate how patients with specific types of cancer are at risk for COVID-19 infection and its adverse outcomes and whether there are cancer-specific race disparities for COVID-19 infection.
Design, Setting, and Participants This retrospective case-control analysis of patient electronic health records included 73.4 million patients from 360 hospitals and 317 000 clinicians across 50 US states to August 14, 2020. The odds of COVID-19 infections for 13 common cancer types and adverse outcomes were assessed.
Exposures The exposure groups were patients diagnosed with a specific cancer, whereas the unexposed groups were patients without the specific cancer.
Main Outcomes and Measures The adjusted odds ratio (aOR) and 95% CI were estimated using the Cochran-Mantel-Haenszel test for the risk of COVID-19 infection.
Results Among the 73.4 million patients included in the analysis (53.6% female), 2 523 920 had at least 1 of the 13 common cancers diagnosed (all cancer diagnosed within or before the last year), and 273 140 had recent cancer (cancer diagnosed within the last year). Among 16 570 patients diagnosed with COVID-19, 1200 had a cancer diagnosis and 690 had a recent cancer diagnosis of at least 1 of the 13 common cancers. Those with recent cancer diagnosis were at significantly increased risk for COVID-19 infection (aOR, 7.14 [95% CI, 6.91-7.39]; P < .001), with the strongest association for recently diagnosed leukemia (aOR, 12.16 [95% CI, 11.03-13.40]; P < .001), non–Hodgkin lymphoma (aOR, 8.54 [95% CI, 7.80-9.36]; P < .001), and lung cancer (aOR, 7.66 [95% CI, 7.07-8.29]; P < .001) and weakest for thyroid cancer (aOR, 3.10 [95% CI, 2.47-3.87]; P < .001). Among patients with recent cancer diagnosis, African Americans had a significantly higher risk for COVID-19 infection than White patients; this racial disparity was largest for breast cancer (aOR, 5.44 [95% CI, 4.69-6.31]; P < .001), followed by prostate cancer (aOR, 5.10 [95% CI, 4.34-5.98]; P < .001), colorectal cancer (aOR, 3.30 [95% CI, 2.55-4.26]; P < .001), and lung cancer (aOR, 2.53 [95% CI, 2.10-3.06]; P < .001). Patients with cancer and COVID-19 had significantly worse outcomes (hospitalization, 47.46%; death, 14.93%) than patients with COVID-19 without cancer (hospitalization, 24.26%; death, 5.26%) (P < .001) and patients with cancer without COVID-19 (hospitalization, 12.39%; death, 4.03%) (P < .001).
Conclusions and Relevance In this case-control study, patients with cancer were at significantly increased risk for COVID-19 infection and worse outcomes, which was further exacerbated among African Americans. These findings highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic.
BMJ JOURNALS
Authors Amanda Zakeri, Ashutosh P Jadhav, Bruce A Sullenger, Shahid M Nimjee
Coronavirus disease 2019 (COVID-19) results from infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first reported in Wuhan, China in patients suffering from severe pneumonia and acute respiratory distress syndrome and has now grown into the first pandemic in over 100 years. Patients infected with SARS-CoV-2 develop arterial thrombosis including stroke, myocardial infarction and peripheral arterial thrombosis, all of which result in poor outcomes despite maximal medical, endovascular, and microsurgical treatment compared with non-COVID-19-infected patients. In this review we provide a brief overview of SARS-CoV-2, the infectious agent responsible for the COVID-19 pandemic, and describe the mechanisms responsible for COVID-19-associated coagulopathy. Finally, we discuss the impact of COVID-19 on ischemic stroke, focusing on large vessel occlusion.
This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.
Authors Davide Lazzeroni, Pietro Concari, Luca Moderato
NATURE MICROBIOLOGY
Authors Smadar Shilo, Hagai Rossman, Barak Mizrahi
Authors Barak Mizrahi, Smadar Shilo, Hagai Rossman, Nir Kalkstein, Karni Marcus, Yael Barer, Ayya Keshet, Na’ama Shamir-Stein, Varda Shalev, Anat Ekka Zohar, Gabriel Chodick, Eran Segal
Authors Ankit Bharat, Melissa Querrey, Nikolay S. Marko, Samuel Kim, Chitaru Kurihara, Rafael Garza-Castillon, Adwaiy Manerikar, Ali Shilatifard, Rade Tomic, Yuliya Politanska, Hiam Abdala-Valencia, Anjana V. Yeldandi, Jon W. Lomasney, Alexander V. Misharin, G.R. Scott Budinger
Abstract Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19-associated respiratory failure. Concerns limiting lung transplantation include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and the potential risk for allograft infection by pathogens causing ventilator-associated pneumonia in the native lung. Importantly, the native lung might recover, resulting in long-term outcomes preferable to those of transplant. Here, we report the results of lung transplantation in three patients with non-resolving COVID-19-associated respiratory failure. We performed single molecule fluorescent in situ hybridization (smFISH) to detect both positive and negative strands of SARS-CoV-2 RNA in explanted lung tissue from the three patients and in additional control lung tissue samples. We conducted extracellular matrix imaging and single cell RNA sequencing on explanted lung tissue from the three patients who underwent transplantation and on warm post-mortem lung biopsies from two patients who had died from COVID-19-associated pneumonia. Lungs from these five patients with prolonged COVID-19 disease were free of SARS-CoV-2 as detected by smFISH, but pathology showed extensive evidence of injury and fibrosis that resembled end-stage pulmonary fibrosis. Using machine learning, we compared single cell RNA sequencing data from the lungs of patients with late stage COVID-19 to that from the lungs of patients with pulmonary fibrosis and identified similarities in gene expression across cell lineages. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is their only option for survival.
Authors Enrico Maria Trecarichi, Maria Mazzitelli, Francesca Serapide, Maria Chiara Pelle, Bruno Tassone, Eugenio Arrighi, Graziella Perri, Paolo Fusco, Vincenzo Scaglione, Chiara Davoli, Rosaria Lionello, Valentina La Gamba, Giuseppina Marrazzo, Maria Teresa Busceti, Amerigo Giudice, Marco Ricchio, Anna Cancelliere, Elena Lio, Giada Procopio, Francesco Saverio Costanzo, Daniela Patrizia Foti, Giovanni Matera, Carlo Torti
Abstract Since December 2019, coronavirus disease 2019 (COVID-19) pandemic has spread from China all over the world and many COVID-19 outbreaks have been reported in long-term care facilities (LCTF). However, data on clinical characteristics and prognostic factors in such settings are scarce. We conducted a retrospective, observational cohort study to assess clinical characteristics and baseline predictors of mortality of COVID-19 patients hospitalized after an outbreak of SARS-CoV-2 infection in a LTCF. A total of 50 patients were included. Mean age was 80 years (SD, 12 years), and 24/50 (57.1%) patients were males. The overall in-hospital mortality rate was 32%. At Cox regression analysis, significant predictors of in-hospital mortality were: hypernatremia (HR 9.12), lymphocyte count < 1000 cells/µL (HR 7.45), cardiovascular diseases other than hypertension (HR 6.41), and higher levels of serum interleukin-6 (IL-6, pg/mL) (HR 1.005). Our study shows a high in-hospital mortality rate in a cohort of elderly patients with COVID-19 and hypernatremia, lymphopenia, CVD other than hypertension, and higher IL-6 serum levels were identified as independent predictors of in-hospital mortality. Given the small population size as major limitation of our study, further investigations are necessary to better understand and confirm our findings in elderly patients.
Authors Mattia Bellan, Giuseppe Patti, Eyal Hayden, Danila Azzolina, Mario Pirisi, Antonio Acquaviva, Gianluca Aimaretti, Paolo Aluffi Valletti, Roberto Angilletta, Roberto Arioli, Gian Carlo Avanzi, Gianluca Avino, Piero Emilio Balbo, Giulia Baldon, Francesca Baorda, Emanuela Barbero, Alessio Baricich, Michela Barini, Francesco Barone-Adesi, Sofia Battistini, Michela Beltrame, Matteo Bertoli, Stephanie Bertolin, Marinella Bertolotti, Marta Betti, Flavio Bobbio, Paolo Boffano, Lucio Boglione, Silvio Borrè, Matteo Brucoli, Elisa Calzaducca, Edoardo Cammarata, Vincenzo Cantaluppi, Roberto Cantello, Andrea Capponi, Alessandro Carriero, Francesco Giuseppe Casciaro, Luigi Mario Castello, Federico Ceruti, Guido Chichino, Emilio Chirico, Carlo Cisari, Micol Giulia Cittone, Crizia Colombo, Cristoforo Comi, Eleonora Croce, Tommaso Daffara, Pietro Danna, Francesco Della Corte, Simona De Vecchi, Umberto Dianzani, Davide Di Benedetto, Elia Esposto, Fabrizio Faggiano, Zeno Falaschi, Daniela Ferrante, Alice Ferrero, Ileana Gagliardi, Gianluca Gaidano, Alessandra Galbiati, Silvia Gallo, Pietro Luigi Garavelli, Clara Ada Gardino, Massimiliano Garzaro, Maria Luisa Gastaldello, Francesco Gavelli, Alessandra Gennari, Greta Maria Giacomini, Irene Giacone, Valentina Giai Via, Francesca Giolitti, Laura Cristina Gironi, Carla Gramaglia, Leonardo Grisafi, Ilaria Inserra, Marco Invernizzi, Marco Krengli, Emanuela Labella, Irene Cecilia Landi, Raffaella Landi, Ilaria Leone, Veronica Lio, Luca Lorenzini, Antonio Maconi, Mario Malerba, Giulia Francesca Manfredi, Maria Martelli, Letizia Marzari, Paolo Marzullo, Marco Mennuni, Claudia Montabone, Umberto Morosini, Marco Mussa, Ilaria Nerici, Alessandro Nuzzo, Carlo Olivieri, Samuel Alberto Padelli, Massimiliano Panella, Andrea Parisini, Alessio Paschè, Alberto Pau, Anita Rebecca Pedrinelli, Ilaria Percivale, Roberta Re, Cristina Rigamonti, Eleonora Rizzi, Andrea Rognoni, Annalisa Roveta, Luigia Salamina, Matteo Santagostino, Massimo Saraceno, Paola Savoia, Marco Sciarra, Andrea Schimmenti, Lorenza Scotti, Enrico Spinoni, Carlo Smirne, Vanessa Tarantino, Paolo Amedeo Tillio, Rosanna Vaschetto, Veronica Vassia, Domenico Zagaria, Elisa Zavattaro, Patrizia Zeppegno, Francesca Zottarelli, Pier Paolo Sainaghi
Abstract Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.
Authors Jessie R. Chung, Sara S. Kim, Michael L. Jackson, Lisa A. Jackson, Edward A. Belongia, Jennifer P. King, Richard K. Zimmerman, Mary Patricia Nowalk, Emily T. Martin, Arnold S. Monto, Manjusha Gaglani, Michael E. Smith, Manish Patel, Brendan Flannery
Abstract We compared symptoms and characteristics of 4961 ambulatory patients with and without laboratory-confirmed SARS-CoV-2 infection. Findings indicate that clinical symptoms alone would be insufficient to distinguish between COVID-19 and other respiratory infections (e.g., influenza) and/or to evaluate the effects of preventive interventions (e.g., vaccinations).
Authors R. Torres-Castro, L. Vasconcello-Castillo, X. Alsina-Restoy, L. Solis-Navarroa, F. Burgos, H. Puppoa,b, J. Vilaró
Abstract Background Evidence suggests lungs as the organ most affected by coronavirus disease 2019 (COVID-19). The literature on previous coronavirus infections reports that patients may experience persistent impairment in respiratory function after being discharged. Our objective was to determine the prevalence of restrictive pattern, obstructive pattern and altered diffusion in patients post-COVID-19 infection and to describe the different evaluations of respiratory function used with these patients. Methods A systematic review was conducted in five databases. Studies that used lung function testing to assess post-infection COVID-19 patients were included for review. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. Results Of the 1973 reports returned by the initial search, seven articles reporting on 380 patients were included in the data synthesis. In the sensitivity analysis, we found a prevalence of 0.39 (CI 0.24–0.56, p < 0.01, I2 = 86%), 0.15 (CI 0.09–0.22, p = 0.03, I2 = 59%), and 0.07 (CI 0.04–0.11, p = 0.31, I2 = 16%) for altered diffusion capacity of the lungs for carbon monoxide (DLCO), restrictive pattern and obstructive pattern, respectively. Conclusion Post-infection COVID-19 patients showed impaired lung function; the most important of the pulmonary function tests affected was the diffusion capacity.
Authors Guillaume Favre, Kevin Legueult, Christian Pradier, Charles Raffaelli, Carole Ichai, Antonio Iannelli, Alban Redheuil, Olivier Lucidarme, Vincent Esnault
Abstract Background Excess visceral fat (VF) or high body mass index (BMI) is risk factors for severe COVID-19. The receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expressed at higher levels in the VF than in the subcutaneous fat (SCF) of obese patients. Aim To show that visceral fat accumulation better predicts severity of COVID-19 outcome compared to either SCF amounts or BMI. Methods We selected patients with symptomatic COVID-19 and a computed tomography (CT) scan. Severe COVID-19 was defined as requirement for mechanical ventilation or death. Fat depots were quantified on abdominal CT scan slices and the measurements were correlated with the clinical outcomes. ACE 2 mRNA levels were quantified in fat depots of a separate group of non-COVID-19 subjects using RT-qPCR. Results Among 165 patients with a mean BMI of 26.1 ± 5.4 kg/m2, VF was associated with severe COVID-19 (p = 0.022) and SCF was not (p = 0.640). Subcutaneous fat was not different in patients with mild or severe COVID-19 and the SCF/VF ratio was lower in patients with severe COVID-19 (p = 0.010). The best predictive value for severe COVID-19 was found for a VF area ≥128.5 cm2 (ROC curve), which was independently associated with COVID-19 severity (p < 0.001). In an exploratory analysis, ACE 2 mRNA positively correlated with BMI in VF but not in SCF of non-COVID-19 patients (r2 = 0.27 vs 0.0008). Conclusion Severe forms of COVID-19 are associated with high visceral adiposity in European adults. On the basis of an exploratory analysis ACE 2 in the visceral fat may be a trigger for the cytokine storm, and this needs to be clarified by future studies. Abbreviations: BMI (body mass index), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), COVID-19 (coronavirus disease 19), RTq-PCR (real-time quantitative polymerase chain reactions), WAT (white adipose tissue), ACE (angiotensin-converting enzyme), CT (computed tomography), RAAS (renin-angiotensin-aldosterone system), VF (visceral fat), SCF (subcutaneous fat)
INTERNATIONAL JOURNAL OF OBESITY
Authors Abdallah Al-Salameh, Jean-Philippe Lanoix, Youssef Bennis, Claire Andrejak, Etienne Brochot, Guillaume Deschasse, Hervé Dupont, Vincent Goeb, Maité Jaureguy, Sylvie Lion, Julien Maizel, Julien Moyet, Benoit Vaysse, Rachel Desailloud, Olivier Ganry, Jean-Luc Schmit, Jean-Daniel Lalau
Abstract Background/Objectives A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study’s primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19. Subjects/Methods Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis. Results In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77–3.24] and 2.58 [1.28–5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29–8.06]) and obesity (3.05 [1.25–7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment. Conclusions Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.
Authors Pinki J Bhatt, Stephanie Shiau, Luigi Brunetti, Yingda Xie, Kinjal Solanki, Shaza Khalid, Sana Mohayya, Pak Ho Au, Christopher Pham, Priyanka Uprety, Ronald Nahass, Navaneeth Narayanan
Authors Valentina Vespro, Maria Carmela Andrisani, Stefano Fusco, Letizia Di Meglio, Guido Plensich, Alice Scarabelli, Elvira Stellato, Anna Maria Ierardi, Luigia Scudeller, Andrea Coppola, Andrea Gori, Antonio Pesenti, Giacomo Grasselli, Stefano Aliberti, Francesco Blasi, Chiara Villa, Sonia Ippolito, Barbara Pirrò, Guglielmo Damiani, Massimo Galli, Giuliano Rizzardini, Emanuele Catena, Matteo Agostino Orlandi, Sandro Magnani, Giuseppe Cipolla, Andrea Antonio Ianniello, Mario Petrillo, Genti Xhepa, Antonio Scamporrino, Alberto Cazzulani, Gianpaolo Carrafiello
Abstract To describe radiographic key patterns on Chest X-ray (CXR) in patients with SARS-CoV-2 infection, assessing the prevalence of radiographic signs of interstitial pneumonia. To evaluate pattern variation between a baseline and a follow-up CXR. 1117 patients tested positive for SARS-CoV-2 infection were retrospectively enrolled from four centers in Lombardy region. All patients underwent a CXR at presentation. Follow-up CXR was performed when clinically indicated. Two radiologists in each center reviewed images and classified them as suggestive or not for interstitial pneumonia, recording the presence of ground-glass opacity (GGO), reticular pattern or consolidation and their distribution. Pearson’s χ2 test for categorical variables and McNemar test (χ2 for paired data) were performed. Patients mean age 63.3 years, 767 were males (65.5%). The main result is the large proportion of positive CXR in COVID-19 patients. Baseline CXR was positive in 940 patients (80.3%), with significant differences in age and sex distribution between patients with positive and negative CXR. 382 patients underwent a follow-up CXR. The most frequent pattern on baseline CXR was the GGO (66.1%), on follow-up was consolidation (53.4%). The most common distributions were peripheral and middle-lower lung zone. We described key-patterns and their distribution on CXR in a large cohort of COVID-19 patients: GGO was the most frequent finding on baseline CXR, while we found an increase in the proportion of lung consolidation on follow-up CXR. CXR proved to be a reliable tool in our cohort obtaining positive results in 80.3% of the baseline cases.
Authors Emily H. Adhikari, Wilmer Moreno, Amanda C. Zofkie, Lorre MacDonald, Donald D. McIntire, Rebecca R. J. Collins, Catherine Y. Spong
Abstract Importance Published data suggest that there are increased hospitalizations, placental abnormalities, and rare neonatal transmission among pregnant women with coronavirus disease 2019 (COVID-19). Objectives To evaluate adverse outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and to describe clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes. Design, Setting, and Participants This observational cohort study of maternal and neonatal outcomes among delivered women with and without SARS-CoV-2 during pregnancy was conducted from March 18 through August 22, 2020, at Parkland Health and Hospital System (Dallas, Texas), a high-volume prenatal clinic system and public maternity hospital with widespread access to SARS-CoV-2 testing in outpatient, emergency department, and inpatient settings. Women were included if they were tested for SARS-CoV-2 during pregnancy and delivered. For placental analysis, the pathologist was blinded to illness severity. Exposures SARS-CoV-2 infection during pregnancy. Main Outcomes and Measures The primary outcome was a composite of preterm birth, preeclampsia with severe features, or cesarean delivery for abnormal fetal heart rate among women delivered after 20 weeks of gestation. Maternal illness severity, neonatal infection, and placental abnormalities were described. Results From March 18 through August 22, 2020, 3374 pregnant women (mean [SD] age, 27.6 [6] years) tested for SARS-CoV-2 were delivered, including 252 who tested positive for SARS-CoV-2 and 3122 who tested negative. The cohort included 2520 Hispanic (75%), 619 Black (18%), and 125 White (4%) women. There were no differences in age, parity, body mass index, or diabetes among women with or without SARS-CoV-2. SARS-CoV-2 positivity was more common among Hispanic women (230 [91%] positive vs 2290 [73%] negative; difference, 17.9%; 95% CI, 12.3%-23.5%; P < .001). There was no difference in the composite primary outcome (52 women [21%] vs 684 women [23%]; relative risk, 0.94; 95% CI, 0.73-1.21; P = .64). Early neonatal SARS-CoV-2 infection occurred in 6 of 188 tested infants (3%), primarily born to asymptomatic or mildly symptomatic women. There were no placental pathologic differences by illness severity. Maternal illness at initial presentation was asymptomatic or mild in 239 women (95%), and 6 of those women (3%) developed severe or critical illness. Fourteen women (6%) were hospitalized for the indication of COVID-19. Conclusions and Relevance In a large, single-institution cohort study, SARS-CoV-2 infection during pregnancy was not associated with adverse pregnancy outcomes. Neonatal infection may be as high as 3% and may occur predominantly among asymptomatic or mildly symptomatic women. Placental abnormalities were not associated with disease severity, and hospitalization frequency was similar to rates among nonpregnant women.
EUROPEAN RESPIRATORY JOURNAL
Authors Anthony W. Martinelli, Tejas Ingle, Joseph Newman, Iftikhar Nadeem, Karl Jackson, Nicholas D. Lane, James Melhorn, Helen E. Davies, Anthony J. Rostron, Aldrin Adeni, Kevin Conroy, Nick Woznitza, Matthew Matson, Simon E. Brill, James Murray, Amar Shah, Revati Naran, Samanjit S. Hare, Oliver Collas, Sarah Bigham, Michael Spiro, Margaret M. Huang, Beenish Iqbal, Sarah Trenfield, Stephane Ledot, Sujal Desai, Lewis Standing, Judith Babar, Razeen Mahroof, Ian Smith, Kai Lee, Nairi Tchrakian, Stephanie Uys, William Ricketts, Anant R.C. Patel, Avinash Aujayeb, Maria Kokosi, Alexander J.K. Wilkinson, Stefan J. Marciniak
Abstract Introduction Pneumothorax and pneumomediastinum have both been noted to complicate cases of coronavirus disease 2019 (COVID-19) requiring hospital admission. We report the largest case series yet described of patients with both these pathologies (including nonventilated patients). Methods Cases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival. Results 71 patients from 16 centres were included in the study, of whom 60 had pneumothoraces (six with pneumomediastinum in addition) and 11 had pneumomediastinum alone. Two of these patients had two distinct episodes of pneumothorax, occurring bilaterally in sequential fashion, bringing the total number of pneumothoraces included to 62. Clinical scenarios included patients who had presented to hospital with pneumothorax, patients who had developed pneumothorax or pneumomediastinum during their inpatient admission with COVID-19 and patients who developed their complication while intubated and ventilated, either with or without concurrent extracorporeal membrane oxygenation. Survival at 28 days was not significantly different following pneumothorax (63.1±6.5%) or isolated pneumomediastinum (53.0±18.7%; p=0.854). The incidence of pneumothorax was higher in males. 28-day survival was not different between the sexes (males 62.5±7.7% versus females 68.4±10.7%; p=0.619). Patients aged ≥70 years had a significantly lower 28-day survival than younger individuals (≥70 years 41.7±13.5% survival versus <70 years 70.9±6.8% survival; p=0.018 log-rank). Conclusion These cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and we encourage continuation of active treatment where clinically possible.
Authors Ehud Rothschild, Guy Baruch, Yishay Szekely, Yael Lichter, Alon Kaplan, Philippe Taieb, Michal Laufer-Perl, Gil Beer, Livia Kapusta, Yan Topilsky
CJO - JCO
Authors Mojtaba Abrishami, Zahra Emamverdian, Naser Shoeibi, Arash Omidtabrizi, Ramin Daneshvar, Talieh Saeidi Rezvani, Neda Saeedian, Saeid Eslami, Mehdi Mazloumi, SriniVas Sadda, David Sarraf
Abstract Objective To quantify the density of the macular microvasculature and the area of the foveal avascular zone (FAZ) in patients recovered from coronavirus disease 2019 (COVID-19) using optical coherence tomography angiography (OCTA) analysis. Methods In a comparative cross-sectional, observational study, patients recovered from COVID-19 were included in this study. All included subjects exhibited a reverse transcription-polymerase chain reaction—confirmed diagnosis of COVID-19. Spectral domain macular OCTA was performed at least 2 weeks after recovery from systemic COVID-19. Vessel density (VD) of the superficial (SCP) and deep retinal capillary plexus (DCP) and the area of the FAZ were measured in COVID-19 recovered patients versus age-matched normal controls. Results Thirty-one recovered COVID-19 patients and 23 healthy normal controls were studied. Mean quality scan index was 7.64 ± 0.66 in the COVID cases and 8.34 ± 0.71 in the normal controls (p = 0.001). Mean SCP VD and DCP VD of the COVID cohort were significantly lower than the SCP VD and DCP VD of the control group in the foveal and parafoveal regions. FAZ area was greater in the COVID cohort, but this difference was not statistically significant. In addition, in the COVID cohort, VD of the SCP and DCP were lower in patients with a history of COVID-19 hospitalization versus those without such a history, but this did not reach statistical significance. Conclusions Patients recovered from COVID-19 displayed alterations in the retinal microvasculature, including a significantly lower VD in the SCP and DCP. Patients with coronavirus infection may be at risk of retinal vascular complications. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic human coronavirus, which can cause serious life-threatening respiratory illness, namely, severe pneumonia,1 and even multiorgan failure.2,3 Despite the growing body of knowledge about various clinical presentations and fatal consequences of coronavirus disease 2019 (COVID-19), reports regarding ocular manifestations are uncommon.4,5 Virus replication starts after binding to epithelial cells in the upper respiratory tract with subsequent propagation and migration down the respiratory tract triggering the innate immune response. Angiotensin-converting enzyme (ACE) 2 has been identified as the main receptor for SARS-CoV26 and its receptors are present in cell membranes of type II alveolar cells in the lung and enterocytes of the small intestine, and also in the arterial and venous endothelial cells and arterial smooth muscle cells of most organs.7 ACE and ACE2 have been found in the choroid and in different cell types of the retina, including Müller cells, ganglion cells, retinal vascular endothelial cells, and photoreceptor cells.9 Reports on the ocular manifestations of COVID-19 mostly describe anterior segment disorders, including conjunctival congestion, chemosis, and conjunctivitis.10,11 Reports of the retinal findings are rare. One group from Brazil12 described various retinal complications of COVID-19, but the validity of this study has been called into question.13 Optical coherence tomography angiography (OCTA) can provide depth-resolved imaging of blood flow in the retina and choroid with microvascular detail that exceeds the capability of other forms of imaging.14 This study evaluated patients previously infected with coronavirus, using OCTA analysis to assess the retinal microvasculature. The objective of this study was to measure the vessel density (VD) of the retinal capillary plexuses and the area of the foveal avascular zone versus an age-matched normal control group.
EUROSURVEILLANCE
Authors Dominique L Monnet, Stephan Harbarth
Authors Anna Palmisano, Giulia Maria Scotti, Davide Ippolito, Marco J. Morelli, Davide Vignale, Davide Gandola , Sandro Sironi, Francesco De Cobelli, Luca Ferrante, Marzia Spessot, Giovanni Tonon, Carlo Tacchetti, Antonio Esposito
Abstract Purpose In overwhelmed emergency departments (EDs) facing COVID-19 outbreak, a swift diagnosis is imperative. CT role was widely debated for its limited specificity. Here we report the diagnostic role of CT in two EDs in Lombardy, epicenter of Italian outbreak. Material and methods Admitting chest CT from 142 consecutive patients with suspected COVID-19 were retrospectively analyzed. CT scans were classified in “highly likely,” “likely,” and “unlikely” COVID-19 pneumonia according to the presence of typical, indeterminate, and atypical findings, or “negative” in the absence of findings, or “alternative diagnosis” when a different diagnosis was found. Nasopharyngeal swab results, turnaround time, and time to positive results were collected. CT diagnostic performances were assessed considering RT-PCR as reference standard. Results Most of cases (96/142, 68%) were classified as “highly likely” COVID-19 pneumonia. Ten (7%) and seven (5%) patients were classified as “likely” and “unlikely” COVID-19 pneumonia, respectively. In 21 (15%) patients a differential diagnosis was provided, including typical pneumonia, pulmonary edema, neoplasia, and pulmonary embolism. CT was negative in 8/142 (6%) patients. Mean turnaround time for the first COVID-19 RT-PCR was 30 ± 13 h. CT diagnostic accuracy in respect of the first test swab was 79% and increased to 91.5% after repeated swabs and/or BAL, for 18 false-negative first swab. CT performance was good with 76% specificity, 99% sensitivity, 90% positive predictive value and 97% negative predictive value. Conclusion Chest CT was useful to streamline patients’ triage while waiting for RT-PCR in the ED, supporting the clinical suspicion of COVID-19 or providing alternative diagnosis.
Authors Roberta Pancani, Liliana Villari, Valentina Foci, Giulia Parri, Francesco Barsotti, Filippo Patrucco, Mario Malerba, Rigoletta Vincenti, Laura Carrozzi, Alessandro Celi
Abstract COVID-19 has been associated with an increased risk of thrombotic events; however, the reported incidence of deep vein thrombosis varies depending, at least in part, on the severity of the disease. Aim of this prospective, multicenter, observational study was to investigate the incidence of lower limb deep vein thrombosis as assessed by compression ultrasound in consecutive patients admitted to three pulmonary medicine wards designated to care for patients with COVID-19 related pneumonia, with or without respiratory failure but not requiring admission to an intensive care unit. Consecutive patients admitted between March 27 and May 6, 2020 were enrolled. Patients were excluded if they were less than 18-year-old or if compression ultrasound could not be performed for any reason. Patients were assessed at admission (t0) and after 7 days (t1). Major and non-major clinically relevant bleedings were recorded. Sixty-eight patients were enrolled. Two were excluded due to anatomical abnormalities that prevented compression ultrasound; sixty patients were retested at (t1). All patients were started on antithrombotic prophylaxis, unless therapeutic anticoagulation was required. Deep vein thrombosis as assessed by compression ultrasound was observed in 2 patients (3%); one of them was later deemed to represent a previous episode. No new episodes were detected at t1. One major and 2 non-major clinically relevant bleedings were observed. In the setting of patients with COVID-related pneumonia not requiring admission to an intensive care unit, the incidence of deep vein thrombosis is low and our data support not screening asymptomatic patients.
Authors Daniel Brito, Scott Meester, Naveena Yanamala, Heenaben B.Pate, Brenden J.Balcik, Grace Casaclang-Verzosa, Karthik Seetharam, Diego Riveros, Robert James Beto, Sudarshan Balla, Aaron J.Monseau, Partho P.Sengupta
Abstract Objectives This study sought to explore the spectrum of cardiac abnormalities in student athletes who returned to university campus in July 2020 with uncomplicated coronavirus disease 2019 (COVID-19). Background There is limited information on cardiovascular involvement in young individuals with mild or asymptomatic COVID-19. Methods Screening echocardiograms were performed in 54 consecutive student athletes (mean age 19 years; 85% male) who had positive results of reverse transcription polymerase chain reaction nasal swab testing of the upper respiratory tract or immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus type 2. Sequential cardiac magnetic resonance imaging was performed in 48 (89%) subjects. Results A total of 16 (30%) athletes were asymptomatic, whereas 36 (66%) and 2 (4%) athletes reported mild and moderate COVID-19 related symptoms, respectively. For the 48 athletes completing both imaging studies, abnormal findings were identified in 27 (56.3%) individuals. This included 19 (39.5%) athletes with pericardial late enhancements with associated pericardial effusion. Of the individuals with pericardial enhancements, 6 (12.5%) had reduced global longitudinal strain and/or an increased native T1. One patient showed myocardial enhancement, and reduced left ventricular ejection fraction or reduced global longitudinal strain with or without increased native T1 values was also identified in an additional 7 (14.6%) individuals. Native T2 findings were normal in all subjects, and no specific imaging features of myocardial inflammation were identified. Hierarchical clustering of left ventricular regional strain identified 3 unique myopericardial phenotypes that showed significant association with the cardiac magnetic resonance findings (p = 0.03). Conclusions More than 1 in 3 previously healthy college athletes recovering from COVID-19 infection showed imaging features of a resolving pericardial inflammation. Although subtle changes in myocardial structure and function were identified, no athlete showed specific imaging features to suggest an ongoing myocarditis. Further studies are needed to understand the clinical implications and long-term evolution of these abnormalities in uncomplicated COVID-19.
Authors Jesse Fajnzylber, James Regan, Kendyll Coxen, Heather Corry, Colline Wong, Alexandra Rosenthal, Daniel Worrall, Francoise Giguel, Alicja Piechocka-Trocha, Caroline Atyeo, Stephanie Fischinger, Andrew Chan, Keith T. Flaherty, Kathryn Hall, Michael Dougan, Edward T. Ryan, Elizabeth Gillespie, Rida Chishti, Yijia Li, Nikolaus Jilg, Dusan Hanidziar, Rebecca M. Baron, Lindsey Baden, Athe M. Tsibris, Katrina A. Armstrong, Daniel R. Kuritzkes, Galit Alter, Bruce D. Walker, Xu Yu, Jonathan Z. Li, The Massachusetts Consortium for Pathogen Readiness
Abstract The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.
Authors Janice Hopkins Tanne
JOURNAL OF CLINICAL MICROBIOLOGY
Authors Andrew M. Borman, Michael D. Palmer, Mark Fraser, Zoe Patterson, Ciara Mann, Debra Oliver, Christopher J. Linton, Martin Gough, Phillipa Brown, Agnieszka Dzietczyk, Michelle Hedley, Sue McLachlan, Julie King, Elizabeth M. Johnson
ABSTRACT COVID-19 associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with acute respiratory distress syndrome following SARS-CoV-2 infection, with incidence rates varying from 8 to 33% depending on the study. However, definitive diagnosis of CAPA is challenging. Standardised diagnostic algorithms and definitions are lacking, clinicians are reticent to perform aerosol-generating bronchoalveolar lavages for galactomannan testing and microscopic and cultural examination, and questions surround the diagnostic sensitivity of different serum biomarkers. Between 11th March and 14th July 2020, the UK National Mycology Reference Laboratory received 1267 serum and respiratory samples from 719 critically ill UK patients with COVID-19 and suspected pulmonary aspergillosis. The laboratory also received 46 isolates of Aspergillus fumigatus from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1000 (1-3)-β-d-glucan and 516 galactomannan tests on serum samples. The results of this extensive testing are presented here. For a subset of 61 patients, respiratory specimens (bronchoalveolar lavages, tracheal aspirates, sputum samples) in addition to serum samples were submitted and subjected to galactomannan testing, Aspergillus-specific PCR and microscopy and culture. The incidence of probable/proven and possible CAPA in this subset of patients was approximately 5% and 15%, respectively. Overall, our results highlight the challenges in biomarker-driven diagnosis of CAPA especially when only limited clinical samples are available for testing, and the importance of a multi-modal diagnostic approach involving regular and repeat testing of both serum and respiratory samples.
PLOS ONE
Authors Yves Allenbach, David Saadoun, Georgina MaaloufI, Matheus Vieira, Alexandra Hellio, Jacques Boddaert, He ́lène Gros, Joe Elie Salem, Matthieu Resche Rigon, Cherifa Menyssa, Lucie Biard, Olivier Benveniste, Patrice Cacoub
Abstract Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward. This French single-center prospective cohort study evaluated 152 patients with positive severe acute respiratory syndrome coronavirus 2 real-time reverse transcriptase–polymerase chain reaction assay, hospitalized in the Internal Medicine and Clinical Immunology Department, at Pitié-Salpêtrière’s Hospital, in Paris, France, a tertiary care university hospital. Predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death) were evaluated in multivariable logistic regression models; models’ performances, including discrimination and calibration, were assessed (C-index, calibration curve, R2, Brier score). A validation was performed on an external sample of 132 patients hospitalized in a French hospital close to Paris, in Aulnay-sous-Bois, Île-de-France. The probability of ICU transfer or death was 32% (47/147) (95% CI 25–40). Older age (OR 2.61, 95% CI 0.96–7.10), poorer respiratory presentation (OR 4.04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1.76–9.25), higher CRP-level (OR 1.63 per 100mg/L increment, 95% CI 0.98–2.71) and lower lymphocytes count (OR 0.36 per 1000/mm3 increment, 95% CI 0.13–0.99) were associated with an increased risk of ICU requirement or death. A 9-point ordinal scale scoring system defined low (score 0–2), moderate (score 3–5), and high (score 6–8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. Therefore, in this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, a simplified scoring system at admission predicted the outcome at D14.
ASSOCIATION OF ANAESTHETISTS
Authors M. Gasparini S. Khan J. M. Patel D. Parekh M. N. Bangash R. Stϋmpfle A. Shah B. Baharlo S. Soni Collaborators
Authors JENNIFER ABBASSI
Authors Lipeng Zhang, Danni He, Wenquan Niu
Authors Carsten Tschöpe, Enrico Ammirati, Biykem Bozkurt, Alida L. P. Caforio, Leslie T. Cooper, Stephan B. Felix, Joshua M. Hare, Bettina Heidecker, Stephane Heymans, Norbert Hübner, Sebastian Kelle, Karin Klingel, Henrike Maatz, Abdul S. Parwani, Frank Spillmann, Randall C. Starling, Hiroyuki Tsutsui, Petar Seferovic, Sophie Van Linthout
Abstract Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.
BMC
Authors Yi Wang, Lin Yao, Jian-Ping Zhang, Pei-Jun Tang, Zhi-Jian Ye, Xing-Hua Shen, Jun-Chi Xu, Mei-Ying Wu, Xin Yu
Abstract Background Sudden exacerbations and respiratory failure are major causes of death in patients with severe coronavirus disease 2019(COVID-19) pneumonia, but indicators for the prediction and treatment of severe patients are still lacking. Methods A retrospective analysis of 67 collected cases was conducted and included approximately 67 patients with COVID-19 pneumonia who were admitted to the Suzhou Fifth People’s Hospital from January 1, 2020 to February 8, 2020. The epidemiological, clinical and imaging characteristics as well as laboratory data of the 67 patients were analyzed. Results The study found that fibrinogen (FIB) was increased in 45 (65.2%) patients, and when FIB reached a critical value of 4.805 g/L, the sensitivity and specificity、DA, helping to distinguish general and severe cases, were 100 and 14%、92.9%, respectively, which were significantly better than those for lymphocyte count and myoglobin. Chest CT images indicated that the cumulative number of lung lobes with lesions in severe patients was significantly higher than that in general patients (P < 0.05), and the cumulative number of lung lobes with lesions was negatively correlated with lymphocyte count and positively correlated with myoglobin and FIB. Our study also found that there was no obvious effect of hormone therapy in patients with severe COVID-19. Conclusions Based on the retrospective analysis, FIB was found to be increased in severe patients and was better than lymphocyte count and myoglobin in distinguishing general and severe patients. The study also suggested that hormone treatment has no significant effect on COVID-19.
Authors Maria J G T Vehreschild, Evelina Tacconelli, Christian G Giske, Andreas Peschel
Authors Sarah H. Berth, Thomas E. Lloyd
Abstract Purpose of review The purpose of this paper is to comprehensively evaluate secondary causes of inflammatory myopathies (myositis) and to review treatment options. Recent findings This review highlights recent advancements in our understanding of known causes of myositis, including newer drugs that may cause myositis such as checkpoint inhibitors and viruses such as influenza, HIV, and SARS-CoV2. We also discuss treatment for malignancy-associated myositis and overlap myositis, thought to be a separate entity from other rheumatologic diseases. Summary Infections, drugs, rheumatologic diseases, and malignancies are important causes of myositis and are important to diagnose as they may have specific therapies beyond immunomodulatory therapy.
Authors Carlos del Rio, Lauren F. Collins, Preeti Malani
Authors Jakob Matschke, Marc Lütgehetmann, Christian Hagel, Jan P Sperhake, Ann Sophie Schröder, Carolin Edler, Herbert Mushumba, Antonia Fitzek, Lena Allweiss, Maura Dandri, Matthias Dottermusch, Axel Heinemann, Susanne Pfefferle, Marius Schwabenland, Daniel Sumner Magruder, Stefan Bonn, Marco Prinz, Christian Gerloff, Klaus Püschel, Susanne Krasemann, Martin Aepfelbacher, Markus Glatzel
Authors Mark M.Hammer, Andetta R.Hunsaker, Mahasweta Gooptu, Hiroto Hatabu
THROMBOSIS RESEARCH
Authors Andrew J. Doyle, Will Thomas, Andrew Retter, Martin Besser, Stephen MacDonald, Karen A. Breen, Michael J.R. Desborough, Beverley J. Hunt
Authors GUGLIELMO LUCCHESE
Authors Priya Mehta Freaney, Sanjiv J. Shah, Sadiya S. Khan
Authors Brandon J Webb, Ithan D Peltan,Paul Jensen, Daanish Hoda, Bradley Hunter, Aaron Silver, Nathan Starr, Whitney Buckel, Nancy Grisel, Erika Hummel, Gregory Snow, Dave Morris, Eddie Stenehjem, Rajendu Srivastava, Samuel M Brown
Authors Meredith Wadman
THE AMERICAN JOURNAL OF CARDIOLOGY
Authors Gaetano Ruocco, Peter A. McCullough, Kristen M. Tecson, Massimo Mancone, Gaetano M. De Ferrari, Fabrizio D’Ascenzo, Francesco G. De Rosa, Anita Paggi, Giovanni Forleo, Gioel G. Secco, Gianfranco Pistis, Silvia Monticone, Marco Vicenzi, Irene Rota, Francesco Blasi, Francesco Pugliese, Francesco Fedele, Alberto Palazzuoli
Authors Anna Schultze, Alex J Walker, Brian MacKenna, Caroline E Morton, Krishnan Bhaskaran, Jeremy P Brown, Christopher T Rentsch, Elizabeth Williamson, Henry Drysdale, Richard Croker, Seb Bacon, William Hulme, Chris Bates, Helen J Curtis, Amir Mehrkar, David Evans, Peter Inglesby, Jonathan Cockburn, Helen I McDonald, Laurie Tomlinson, Rohini Mathur, Kevin Wing, Angel Y S Wong, Harriet Forbes, John Parry, Frank Hester, Sam Harper, Stephen J W Evans, Jennifer Quint, Liam Smeeth, Ian J Douglas, Ben Goldacre
Authors George N. Ioannou, Emily Locke, Pamela Green, Kristin Berry, Ann M. O’Hare, Javeed A. Shah, Kristina Crothers, McKenna C. Eastment, Jason A. Dominitz, Vincent S. Fan
Abstract Importance Identifying independent risk factors for adverse outcomes in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can support prognostication, resource utilization, and treatment. Objective To identify excess risk and risk factors associated with hospitalization, mechanical ventilation, and mortality in patients with SARS-CoV-2 infection. Design, Setting, and Participants This longitudinal cohort study included 88 747 patients tested for SARS-CoV-2 nucleic acid by polymerase chain reaction between Feburary 28 and May 14, 2020, and followed up through June 22, 2020, in the Department of Veterans Affairs (VA) national health care system, including 10 131 patients (11.4%) who tested positive. Exposures Sociodemographic characteristics, comorbid conditions, symptoms, and laboratory test results. Main Outcomes and Measures Risk of hospitalization, mechanical ventilation, and death were estimated in time-to-event analyses using Cox proportional hazards models. Results The 10 131 veterans with SARS-CoV-2 were predominantly male (9221 [91.0%]), with diverse race/ethnicity (5022 [49.6%] White, 4215 [41.6%] Black, and 944 [9.3%] Hispanic) and a mean (SD) age of 63.6 (16.2) years. Compared with patients who tested negative for SARS-CoV-2, those who tested positive had higher rates of 30-day hospitalization (30.4% vs 29.3%; adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.13), mechanical ventilation (6.7% vs 1.7%; aHR, 4.15; 95% CI, 3.74-4.61), and death (10.8% vs 2.4%; aHR, 4.44; 95% CI, 4.07-4.83). Among patients who tested positive for SARS-CoV-2, characteristics significantly associated with mortality included older age (eg, ≥80 years vs <50 years: aHR, 60.80; 95% CI, 29.67-124.61), high regional COVID-19 disease burden (eg, ≥700 vs <130 deaths per 1 million residents: aHR, 1.21; 95% CI, 1.02-1.45), higher Charlson comorbidity index score (eg, ≥5 vs 0: aHR, 1.93; 95% CI, 1.54-2.42), fever (aHR, 1.51; 95% CI, 1.32-1.72), dyspnea (aHR, 1.78; 95% CI, 1.53-2.07), and abnormalities in the certain blood tests, which exhibited dose-response associations with mortality, including aspartate aminotransferase (>89 U/L vs ≤25 U/L: aHR, 1.86; 95% CI, 1.35-2.57), creatinine (>3.80 mg/dL vs 0.98 mg/dL: aHR, 3.79; 95% CI, 2.62-5.48), and neutrophil to lymphocyte ratio (>12.70 vs ≤2.71: aHR, 2.88; 95% CI, 2.12-3.91). With the exception of geographic region, the same covariates were independently associated with mechanical ventilation along with Black race (aHR, 1.52; 95% CI, 1.25-1.85), male sex (aHR, 2.07; 95% CI, 1.30-3.32), diabetes (aHR, 1.40; 95% CI, 1.18-1.67), and hypertension (aHR, 1.30; 95% CI, 1.03-1.64). Notable characteristics that were not significantly associated with mortality in adjusted analyses included obesity (body mass index ≥35 vs 18.5-24.9: aHR, 0.97; 95% CI, 0.77-1.21), Black race (aHR, 1.04; 95% CI, 0.88-1.21), Hispanic ethnicity (aHR, 1.03; 95% CI, 0.79-1.35), chronic obstructive pulmonary disease (aHR, 1.02; 95% CI, 0.88-1.19), hypertension (aHR, 0.95; 95% CI, 0.81-1.12), and smoking (eg, current vs never: aHR, 0.87; 95% CI, 0.67-1.13). Most deaths in this cohort occurred in patients with age of 50 years or older (63.4%), male sex (12.3%), and Charlson Comorbidity Index score of at least 1 (11.1%). Conclusions and Relevance In this national cohort of VA patients, most SARS-CoV-2 deaths were associated with older age, male sex, and comorbidity burden. Many factors previously reported to be associated with mortality in smaller studies were not confirmed, such as obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking.
Authors Mia Ahlberg, Martin Neovius, Sissel Saltvedt, Jonas Söderling, Karin Pettersson, Clara Brandkvist, Olof Stephansson
Authors Rita Rubin
Authors Charlotte F. Tisch
Authors Abderrahim Oussalah, Stanislas Gleye, Isabelle Clerc Urmes, Elodie Laugeld, Francoise Barb, Sophie Orlowski, Catherine Malaplate, Isabelle Aimone-Gastin, Beatrice Maatem Caillierez, Marc Mertena, Elise Jeannesson, Raphael Kormann, Jean-Luc Olivier, Rosa-Maria Rodriguez-Gueant, Fares Namour, Sybille Bevilacqua, Nathalie Thilly, Marie-Reine Losser, Antoine Kimmoun, Luc Frimat, Bruno Levyi, Sebastien Gibot, Evelyne Schvoererd, Jean-Louis Gueant
Abstract Background In patients with severe COVID-19, no data are available on the longitudinal evolution of biochemical abnormalities and their ability to predict disease outcomes. Methods Using a retrospective, longitudinal cohort study design on consecutive patients with severe COVID-19, we used an extensive biochemical dataset of serial data and time-series design to estimate the occurrence of organ dysfunction and the severity of the inflammatory reaction and their association with acute respiratory failure (ARF) and death. Findings On the 162 studied patients, 1151 biochemical explorations were carried out for up to 59 biochemical markers, totaling 15,260 biochemical values. The spectrum of biochemical abnormalities and their kinetics were consistent with a multi-organ involvement, including lung, kidney, heart, liver, muscle, and pancreas, along with a severe inflammatory syndrome. The proportion of patients who developed an acute kidney injury (AKI) stage 3, increased significantly during follow-up (0·9%, day 0; 21·4%, day 14; P<0·001). On the 20 more representative biochemical markers (>250 iterations), only CRP >90 mg/L (odds ratio [OR] 6·87, 95% CI, 2·36–20·01) and urea nitrogen >0·36 g/L (OR 3·91, 95% CI, 1·15–13·29) were independently associated with the risk of ARF. Urea nitrogen >0·42 g/L was the only marker associated with the risk of COVID-19 related death. Interpretation Our results point out the lack of the association between the inflammatory markers and the risk of death but rather highlight a significant association between renal dysfunction and the risk of COVID-19 related acute respiratory failure and death.
NMCD
Authors Augusto Di Castelnuovo, Marialaura Bonaccio, Simona Costanzo, Alessandro Gialluisi, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Raffaele Bruno, Roberto Cauda, Giovanni Guaraldi, Ilaria My, Lorenzo Menicanti, Agostino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G. Stefanini, Alessandra Vergori, Amina Abdeddaim, Walter Ageno, Antonella Agodi, Piergiuseppe Agostoni, Luca Aiello, Samir Al Moghazi, Filippo Aucella, Greta Barbieri, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Serena Brancati, Francesco Cacciatore, Lucia Caiano, Francesco Cannata, Laura Carrozzi, Antonio Cascio, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Annalisa Crisetti, Francesco Crosta, Gian Battista Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Gisella Di Palma, Giuseppe Di Tano, Massimo Fantoni, Tommaso Filippini, Paola Fioretto, Francesco Maria Fusco, Ivan Gentile, Leonardo Grisafi, Gabriella Guarnieri, Francesco Landi, Giovanni Larizza, Armando Leone, Gloria Maccagni, Sandro Maccarella, Massimo Mapelli, Riccardo Maragna, Rossella Marcucci, Giulio Maresca, Claudia Marotta, Lorenzo Marra, Franco Mastroianni, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Rita Miurri, Arturo Montineri, Roberta Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Francesco Petri, Biagio Pinchera, Carlo A. Pivato, Roberto Pizzi, Venerino Poletti, Francesca Raffaelli, Claudia Ravaglia, Giulia Righetti, Andrea Rognoni, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Antonio Scarafino, Laura Scorzolini, Raffaella Sgariglia, Paola Giustina Simeone, Enrico Spinoni, Carlo Torti, Enrico Maria Trecarichi, Francesca Vezzani, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Raffaele De Caterina, Licia Iacoviello, THE COVID-19 RISK and Treatments (CORIST) collaboration
Abstract Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.
Authors Davide Mangioni, Daniele Dondossola, Barbara Antonelli, Laura Alagna, Federica Invernizzi, Federico Polli, Giulia Tosetti, Antonio Muscatello, Andrea Gori, Giorgio Rossi
We have read with great interest the article by Polak et al. on the behalf of the European Liver and Intestine Transplant Association (ELITA) and the European Liver Transplant Registry (ELTR) recently published in your Journal [1]. The authors provided valuable information on incidence and mortality of coronavirus disease 2019 (COVID‐19) among liver transplant (LT) candidates and recipients in Europe. They also gave a clear picture on current practices of donor and recipient management among several European LT Centers
Authors Michael Marshall
Authors Anitha Vijayan, Benjamin D. Humphreys
Authors Zhenyu Kang, Shanshan Luo, Yang Gui, Haifeng Zhou, Zili Zhang, Chunxia Tian, Qiaoli Zhou, Quansheng Wang, Yu Hu, Heng Fan, Desheng Hu
Abstract Background Since December 2019, novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. COVID-19 patients demonstrated significantly different outcomes in clinic. We aimed to figure out whether obesity is a risk factor influencing the progression and prognosis of COVID-19. Methods 95 patients with COVID-19 were divided into obesity group and non-obesity group according to their body mass index (BMI). The demographic data, clinical characteristics, laboratory examination, and chest computed tomography (CT) were collected, analyzed and compared between two groups. Results Our data showed that COVID-19 patients with obesity had more underlying diseases and higher mortality rate compared to those without obesity. Furthermore, patients with obesity also demonstrated more severe pathological change in lung and higher blood lymphocytes, triglycerides, IL-6, CRP, cystatin C, alanine aminotransferase (ALT), erythrocyte sedimentation rate (ESR), which may greatly influence disease progression and poor prognosis of COVID-19. Conclusions It suggest that obesity contributes to clinical manifestations and may influence the progression and prognosis of COVID-19 and it is considered as a potential risk factor of the prognosis of COVID-19. Special medical care and appropriate intervention should be performed in obesity patients with COVID-19 during hospitalization and later clinical follow-up, especially for those with additional other comorbidities.
Authors Saurabh Rajpal, Matthew S. Tong, James Borchers, Karolina M. Zareba, Timothy P. Obarski, Orlando P. Simonetti, Curt J. Daniels
Authors P Lewis White, Rishi Dhillon, Harriet Hughes, Matthew P Wise, Matthijs Backx
Authors Giovanni Andrea Gerardo Crameri, Michel Bielecki, Roland Züst, Thomas Werner Buehrer, Zeno Stanga, Jeremy Werner Deuel
ABSTRACT In March 2020, we observed an outbreak of COVID-19 among a relatively homogenous group of 199 young (median age 21 years; 87% men) Swiss recruits. By comparing physical endurance before and in median 45 days after the outbreak, we found a significant decrease in predicted maximal aerobic capacity in COVID-19 convalescent but not in asymptomatically infected and SARS-CoV-2 naive recruits. This finding might be indicative of lung injury after apparently mild COVID-19 in young adults.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
Authors Dinesh Jothimani, Ezhilarasan Kailasam, Silas Danielraj, Balaji Nallathambi, Hemalatha Ramachandran, Padmini Sekar, Shruthi Manoharan, Vidyalakshmi Ramani, Gomathy Narasimhan, Ilankumaran Kaliamoorthy, Mohamed Rela
Abstract Background Zinc is a trace element with potent immunoregulatory, antiviral properties and is utilized in the treatment of COVID-19. However, we do not know the clinical significance of serum Zinc level in COVID-19 patients. Aim To determine the clinical significance of serum Zinc in COVID-19 patients and to establish a correlation with disease severity. Methodology A prospective study on COVID-19 patients underwent fasting Zinc level at the time of hospitalisation. An initial comparative analysis was carried out between COVID-19 patients and healthy controls. Zinc deficiency COVID-19 patients were compared to those with normal levels. Results COVID-19 patients (n = 47) showed significantly low Zinc levels compared to healthy controls (n = 45), median 74.5 (IQR 53.4-94.6) vs 105.8 (IQR 95.65120.90) µg/dl, P < 0.001. Amongst COVID-19 positive patients, 27 (57.4%) were found Zinc deficient. These patients were found to have higher complications (P = 0.009), ARDS (18.5% vs 0%, P = 0.06), received corticosteroid therapy (P = 0.02), prolonged hospital stay (P = 0.05) and increased mortality (18.5% vs 0%, P = 0.06). The Odds ratio (OR) of developing complications in Zinc deficient COVID-19 patients was 5.54. Conclusion Our data clearly shows that significant number of COVID-19 patients are Zinc deficient. These Zinc deficient patients developed more complications with prolonged hospital stay and were associated with increased mortality.
RESUSCITATION
Authors Marcello Covino, Claudio Sandroni, Michele Santoro, Luca Sabia, Benedetta Simeoni, Maria Grazia Bocci, Veronica Ojetti, Marcello Candelli, Massimo Antonelli, Antonio Gasbarrini, Francesco Franceschi
Aims: To identify the most accurate early warning score (EWS) for predicting an adverse outcome in COVID-19 patients admitted to the emergency department (ED). Methods: In adult consecutive patients admitted (March 1-April 15, 2020) to the ED of a major referral centre for COVID-19, we retrospectively calculated NEWS, NEWS2, NEWS-C, MEWS, qSOFA, and REMS from physiological variables measured on arrival. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and the area under the receiver operating characteristic (AUROC) curve of each EWS for predicting admission to the intensive care unit (ICU) and death at 48 h and 7 days were calculated. Results: We included 334 patients (119 [35.6%] females, median age 66 [54-78] years). At 7 days, the rates of ICU admission and death were 56/334 (17%) and 26/334 (7.8%), respectively. NEWS was the most accurate predictor of ICU admission within 7 days (AUROC 0.783 [95% CI, 0.735-0.826]; sensitivity 71.4 [57.8-82.7]%; NPV 93.1 [89.8-95.3]%), while REMS was the most accurate predictor of death within 7 days (AUROC 0.823 [0.778 0.863]; sensitivity 96.1 [80.4-99.9]%; NPV 99.4[96.299.9]%). Similar results were observed for ICU admission and death at 48 h. NEWS and REMS were as accurate as the triage system used in our ED. MEWS and qSOFA had the lowest overall accuracy for both outcomes. Conclusion: In our single-centre cohort of COVID-19 patients, NEWS and REMS measured on ED arrival were the most sensitive predictors of 7-day ICU admission or death. EWS could be useful to identify patients with low risk of clinical deterioration.
Authors Stephen R Knight, Antonia Ho, Riinu Pius, Iain Buchan, Gail Carson, Thomas M Drake, Jake Dunning, Cameron J Fairfield, Carrol Gamble, Christopher A Green, Rishi Gupta, Sophie Halpin, Hayley E Hardwick, Karl A Holden, Peter W Horby, Clare Jackson, Kenneth A Mclean, Laura Merson, Jonathan S Nguyen-Van-Tam, Lisa Norman, Mahdad Noursadeghi Piero L Olliaro, Mark G Pritchard, Clark D Russell, Catherine A Shaw, Aziz Sheikh, Tom Solomon, Cathie Sudlow, Olivia V Swann, Lance CW Turtle, Peter JM Openshaw, J Kenneth Baillie, Malcolm G Semple, Annemarie B Docherty, Ewen M Harrison
Abstract Objective To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19). Design Prospective observational cohort study. Setting International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium—ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020. Participants Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction. Main outcome measure In-hospital mortality. Results 35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73). Conclusions An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.
Authors Matteo Bassetti, Marin H. Kollef, Jean-Francois Timsit
Authors Griffin P. Rodgers; Gary H. Gibbons
Authors Angela Coulter, Tessa Richards
Authors Nikki Nabavi
Authors Giuseppe La Torre, Anna Paola Massetti, Guido Antonelli, Caterina Fimiani, Mauro Fantini, Mattia Marte, Augusto Faticoni, Carlo Maria Previte, Ombretta Turriziani, Francesco Pugliese, Paolo Villari, Ferdinando Romano, Claudio Maria Mastroianni
Background: The aim of this study was to investigate the diagnostic accuracy of symptoms and signs in healthcare workers (HCW) with Sars-CoV-2. Methods: This was a case-control study. Cases consisted of symptomatic healthcare workers who had a positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test, while controls were symptomatic healthcare workers with a negative RT-PCR test. For each symptom, ROCs were plotted. Diagnostic accuracy was calculated using the sensitivity, specificity, and positive and negative predictive values. A logistic regression analysis was carried out for calculating the OR (95% CI) for each symptom associated to the SARS-CoV-2 positivity. Results: We recruited 30 cases and 75 controls. Fever had the best sensitivity while dyspnea, anosmia, and ageusia had the highest specificity. The highest PPVs were found again for dyspnea (75%), anosmia (73.7%), and ageusia (66.7%). Lastly, the highest NPVs were related to anosmia (81.4%) and ageusia (79.3%). Anosmia (OR = 14.75; 95% CI: 4.27–50.87), ageusia (OR = 9.18; 95% CI: 2.80–30.15), and headache (OR = 3.92; 95% CI: 1.45–10.56) are significantly associated to SARS-CoV-2 positivity. Conclusions: Anosmia and ageusia should be considered in addition to the well-established fever, cough, and dyspnea. In a resource-limited setting, this method could save time and money.
Authors Peter Libby, Thomas Lüscher
ABSTRACT The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis. This tightly regulated palette of functions includes control of haemostasis, fibrinolysis, vasomotion, inflammation, oxidative stress, vascular permeability, and structure. While these functions participate in the moment-to-moment regulation of the circulation and coordinate many host defence mechanisms, they can also contribute to disease when their usually homeostatic and defensive functions over-reach and turn against the host. SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic. It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems including the lungs, heart, brain, kidney, and vasculature. This essay explores the hypothesis that COVID-19, particularly in the later complicated stages, represents an endothelial disease. Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode. The endgame of COVID-19 usually involves a cytokine storm, a phlogistic phenomenon fed by well-understood positive feedback loops that govern cytokine production and overwhelm counter-regulatory mechanisms. The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic.
EUROPEAN JOURNAL OF CANCER
Authors Kamal S. SainI, Marco Tagliamento, Matteo Lambertini, Richard McNally, Marco Romano, Manuela Leone, Giuseppe Curigliano, Evandro de Azambuja
Abstract Background Patients with coronavirus disease 2019 (COVID-19) who have underlying malignancy have a higher mortality rate compared with those without cancer, although the magnitude of such excess risk is not clearly defined. We performed a systematic review and pooled analysis to provide precise estimates of the mortality rate among patients with both cancer and COVID-19. Methods A systematic literature search involving peer-reviewed publications, preprints and conference proceedings up to July 16, 2020, was performed. The primary end-point was the case fatality rate (CFR), defined as the rate of death among patients with cancer and COVID-19. The CFR was assessed with a random effects model, which was used to derive a pooled CFR and its 95% confidence interval (CI). Results Fifty-two studies, involving a total of 18,650 patients with both COVID-19 and cancer, were selected for the pooled analysis. A total of 4243 deaths were recorded in this population. The probability of death was 25.6% (95% CI: 22.0%–29.5%; I2 = 48.9%) in this patient population. Conclusions Patients with cancer who develop COVID-19 have high probability of mortality. Appropriate and aggressive preventive measures must be taken to reduce the risk of COVID-19 in patients with cancer and to optimally manage those who do contract the infection.
SARS CoV 2 in severe neurological patients
MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES
Authors Francesco Di Gennaro
ABSTRACT Introduction: Patients admitted to intensive neurorehabilitation facilities following neurological damage who developed SARS-CoV-2 infection during hospitalization have not yet been reported. Such patients are elderly, with severe disabling neurological syndromes, more likely have significant underlying comorbidities and develop fatal complications during the disease. We reported clinical features, underlying comorbidities, laboratory and radiological findings, treatment and outcome of severely disabled neurological patients with SARS-CoV-2 infection. Methods: We retrospectively analyzed a group of 14 patients affected by severe neurological damage previously admitted to the Neurorehabilitation Unit of Neuromed Research Institute in Pozzilli, Italy, who developed confirmed COVID-19 during a SARS-CoV-2 outbreak occurred on March, 2020. Results: One out of 14 patients (7%) died after developing a severe acute respiratory distress. The remaining patients did not present any symptom or laboratory or radiological signs of the disease; neither new neurological deficit nor worsening of the pre-existing clinical manifestations were observed. Thirtheen patients had underlying comorbitidies (93%), the most frequent being hypertension (11 patients, 78.5%) and diabetes mellitus type II (7 patients, 50%). Long before infection, all patients were already under anticoagulant therapy with enoxaparin. Conclusions: In 13 out of 14 patients, the infection was asymptomatic; this is particularly intriguing considering their severe neurological clinical profile. According to the pivotal role played by inflammation and activation of blood coagulation in the pathogenesis of COVID-19, the anti-inflammatory and anticoagulant properties of enoxaparin, administered much earlier and during infection, could have favored an extremely benign disease course in these patients at high risk of poor outcome.
Authors Ming-Yen Ng, Vanessa M. Ferreira, Phily Siu Ting Leung, Jonan Chun Yin Lee, Ambrose Ho-Tung Fong, Raymond Wai To Liu, Johnny Wai Man Chan, Alan Ka Lun Wu, Kwok-Cheung Lung, Andrew M. Crean, Ivan Fan-Ngai Hung, Chung-Wah Siu
Authors Kristoffer Grundtvig Skaarup, Mats Christian Højbjerg Lassen, Jannie Nørgaard Lind, Alia Saed Alhakak, Morten Sengeløv, Anne Bjerg Nielsen, Caroline Espersen, Raphael Hauser, Liv Borum Schöps, Eva Holt, Niklas Dyrby Johansen,Daniel Modin, Shreeya Sharma, Claus Graff, Henning Bundgaard, Christian Hassager, Reza Jabbari, Anne-Mette Lebech, Ole Kirk, Uffe Bødtger, Matias Greve Lindholm, Gowsini Joseph, Lothar Wiese, Frank Vinholt Schiødt, Ole Peter Kristiansen, Emil Schwarz Walsted, Olav Wendelboe Nielsen, Birgitte Lindegaard Madsen, Niels Tønder, Thomas Lars Benfield, Klaus Nielsen Jeschke, Charlotte Suppli Ulrik, Filip Knop, Jannik Pallisgaard, Morten Lamberts, Pradeesh Sivapalan, Gunnar Gislason, Scott D. Solomon, Kasper Iversen, Jens Ulrik Stæhr Jensen, Morten Schou,Tor Biering-Sørensen
Authors S. Rizza, L. Coppeta, S. Grelli, G. Ferrazza, M. Chiocchi, G. Vanni, O. C. Bonomo, A. Bellia, M. Andreoni, A. Magrini, M. Federici
ABSTRACT Objective To assess the magnitude of COVID-19 spread and the associated risk factors among health care workers (HCWs), we conducted an in-hospital survey in a central Italian COVID Hospital. Methods Participants underwent nasopharyngeal swab and/or serum collection for SARS-CoV-2 IgG examination. We divided participants according to working status, into rotating-night shift workers (r-NSW) and day-workers. Results We found 30 cases of COVID-19 infection in a total of 1180 HCWs (2.5%). Most COVID-19-positive hospital employees were r-NSWs with significantly higher BMI than that of individuals who tested negative. After adjustment for covariates, night work and BMI > 30 were associated with a markedly greater risk of COVID-19 diagnosis (OR 3.049 [95%CI 1.260–7.380] and OR 7.15 [95%CI 2.91–17.51], respectively). Conclusions Our results describe a low prevalence of COVID-19 infection among HCWs at a central Italian COVID Hospital. COVID-19 infection risk appears to be associated with obesity and night shift work, thus supporting the need for careful health surveillance among frontline HCWs exposed to COVID-19.
Authors JANE PERRY
Authors Barry M. Popkin Shufa Du William D. Green Melinda A. Beck Taghred Algaith Christopher H. Herbst Reem F. Alsukait Mohammed Alluhidan Nahar Alazemi Meera Shekar
Authors Miao Wang, Qiguo Zhu, Jianguo Fu, Lilong Liu, Mingzhe Xiaof, Yu Dub
Abstract Background A variety of inflammatory and non-inflammatory indicators were increased in severe and critical Coronavirus disease-19 (COVID-19) and some of them were used to evaluate the severity and predict prognosis of community-acquired pneumonia. The aim of this study was to investigate the association of these indicators in COVID-19 with different severity. Methods Clinical data of 46 patients with severe COVID-19 and 31 patients with critical COVID-19 were collected. The general characteristics and comorbidities of the patients were retrospectively analyzed. The initial and peak concentrations of serum troponin I (cTnI), D-dimer (D-D), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), initial and peak neutrophil counts and initial and trough lymphocyte counts were compared between two groups. The correlation between the variation of cTnI, D-D, CRP, IL-6, PCT, neutrophils, lymphocytes and the severity of the disease was analyzed. The efficacy of the initial concentrations of cTnI, D-D, CRP, IL-6, PCT, the initial neutrophil and lymphocyte counts in predicting critical COVID-19 were evaluated by receiver operating characteristic (ROC) curve. Results The initial and peak concentrations of cTnI, D-D, CRP, IL-6, PCT, initial and peak neutrophil counts in critical group were higher than those in severe group, the initial and trough counts of lymphocyte were lower than those in the severe group. Except for the initial level of PCT, the other differences were statistically significant (p < 0.05). The increase of cTnI, D-D, CRP, IL-6, PCT, neutrophils and the decrease of lymphocytes were related to the severity of the disease, OR values were 28.80, 2.20, 18.47, 10.80, 52.00, 9.60 and 21.08, respectively. Except for D-D, the other differences were statistically significant. The areas under ROC curves for predicting critical COVID-19 by initial concentrations of cTnI, D-D, CRP, IL-6, PCT, initial lymphocyte and neutrophil counts were 0.76, 0.78, 0.83, 0.95, 0.56, 0.68 and 0.62, respectively. Conclusions The severe and critical COVID-19 patients had significant differences in concentrations of serum cTnI, D-D, CRP, IL-6, PCT, neutrophil and lymphocyte counts. The increase of cTnI, CRP, IL-6, PCT, neutrophils and decrease of lymphocytes indicated severe condition. The initial IL-6 might be a good indicator of COVID-19 severity.
AMERICAN DIABETES ASSOCIATION
Authors ohn Xie, Yuanhao Zu, Ala Alkhatib, Thaidan T. Pham, Frances Gill, Albert Jang, Stella Radosta, Gerard Chaaya, Leann Myers, Jerry S. Zifodya, Christine M. Bojanowski, Nassir F. Marrouche, Franck Mauvais-Jarvis, Joshua L. Denson
Abstract OBJECTIVE Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity, and diabetes. We examined the association between hypertension, obesity, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak. RESEARCH DESIGN AND METHODS Data were collected from 287 consecutive patients with COVID-19 hospitalized at two hospitals in New Orleans, LA from 30 March to 5 April 2020. MetS was identified per World Health Organization criteria. RESULTS Among 287 patients (mean age 61.5 years; female, 56.8%; non-Hispanic black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR] 3.42 [95% CI 1.52–7.69]), intensive care unit (ICU) (aOR 4.59 [CI 2.53–8.32]), invasive mechanical ventilation (IMV) (aOR 4.71 [CI 2.50–8.87]), and acute respiratory distress syndrome (ARDS) (aOR 4.70 [CI 2.25–9.82]) compared with non-MetS. Multivariable analyses of hypertension, obesity, and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR 2.18 [CI, 1.25–3.81]), ARDS (aOR 2.44 [CI 1.28–4.65]), and IMV (aOR 2.36 [CI 1.33–4.21]). Diabetes was associated with ICU (aOR 2.22 [CI 1.24–3.98]) and IMV (aOR 2.12 [CI 1.16–3.89]). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, CRP, and lactate dehydrogenase (LDH) were associated with mortality (CRP [aOR 3.66] [CI 1.22–10.97] and LDH [aOR 3.49] [CI 1.78–6.83]). CONCLUSIONS In predominantly black patients hospitalized for COVID-19, the clustering of hypertension, obesity, and diabetes as MetS increased the odds of mortality compared with these comorbidities individually.
Authors Diane Marie Del Valle, Seunghee Kim-Schulze, Hsin-Hui Huang, Noam D. Beckmann, Sharon Nirenberg, Bo Wang, Yonit Lavin, Talia H. Swartz, Deepu Madduri, Aryeh Stock, Thomas U. Marron, Hui Xie, Manishkumar Patel, Kevin Tuballes, Oliver Van Oekelen, Adeeb Rahman, Patricia Kovatch, Judith A. Aberg, Eric Schadt, Sundar Jagannath, Madhu Mazumdar, Alexander W. Charney, Adolfo Firpo-Betancourt, Damodara Rao Mendu, Jeffrey Jhang, David Reich, Keith Sigel, Carlos Cordon-Cardo, Marc Feldmann, Samir Parekh, Miriam Merad, Sacha Gnjatic
ABSTRACT Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.
Authors Antonio Novelli Marco Andreani Michela Biancolella Laura Liberatoscioli Chiara Passarelli Vito Luigi Colona Paola Rogliani Francesca Leonardis Andrea Campana Rita Carsetti Massimo Andreoni Sergio Bernardini Giuseppe Novelli Franco Locatelli
ABSTRACT With the aim to individuate alleles that may reflect a higher susceptibility to the disease, in the present study we analyzed the HLA allele frequency distribution in a group of 99 Italian patients affected by a severe or extremely severe form of COVID‐19. After the application of Bonferroni's correction for multiple tests, a significant association was found for HLA‐DRB1*15:01, ‐DQB1*06:02 and ‐B*27:07, after comparing the results to a reference group of 1017 Italian individuals, previously typed in our laboratory. The increased frequencies observed may contribute to identify potential markers of susceptibility to the disease, although controversial results on the role of single HLA alleles in COVID‐19 patients have been recently reported.
Authors Gregory Dendramis, Pedro Brugada
ABSTRACT Coronavirus disease 2019 (COVID‐19) spreads across the world and the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic viral infection. Rapid diagnosis, isolation and intensive clinical management, are very important for all patients with COVID‐19, especially for those with cardiac diseases as Brugada syndrome (BrS). BrS is an arrhythmogenic disease reported to be one among the leading causes of sudden cardiac death. In these patients episodes of lethal arrhythmias may be induced by several factors or situations and for this reason management during ICU permanence or anesthesia must provides some precautions, avoiding factors that are known to have the potential to worsen the probability to induce arrhythmias. For ICU practitioners, management of acute respiratory failure, haemodynamics and cardiovascular complications certainly are the key for the best treatment of these patients but to date specific data on supportive ICU care for these patients are lacking and current recommendations are based on existing evidence from other viral infections and general intensive care management. We want to focus on some general rules, resulted from cases series and clinical practice, to be followed during the ICU management of patients with BrS and concomitant COVID‐19 infection.
Authors Dimitrios Patoulias, Alexandra Katsimardou, Christodoulos Papadopoulos, Michael Doumas
SAGE JOURNALS
Authors Dan J. Cuthbertson, William Henry Duncan , Uazman Alam, Abd Tahrani
Authors Stefano Pallanti, Eleonora Grassi, Nikos Makris, Gregory P.Gasic, Eric Hollander
Abstract Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, is a disaster due to not only its psychosocial impact but it also to its direct effects on the brain. The latest evidence suggests it has neuroinvasive mechanisms, in addition to neurological manifestations, and as seen in past pandemics, long-term sequelae are expected. Specific and well-structured interventions are necessary, and that's why it's important to ensure a continuity between primary care, emergency medicine, and psychiatry. Evidence shows that 2003 SARS (Severe Acute Respiratory Syndrome) survivors developed persistent psychiatric comorbidities after the infection, in addition to Chronic Fatigue Syndrome. A proper stratification of patients according not only to psychosocial factors but also an inflammatory panel and SARS-Cov-2's direct effects on the central nervous system (CNS) and the immune system, may improve outcomes. The complexity of COVID-19's pathology and the impact on the brain requires appropriate screening that has to go beyond the psychosocial impact, taking into account how stress and neuroinflammation affects the brain. This is a call for a clinical multidisciplinary approach to treat and prevent Sars-Cov-2 mental health sequelae.
Authors Michuki Maina, Olga Tosas-Auguet, Mike English, Constance Schultsz, Jacob McKnight
Authors Hoyt Burdick, Carson Lam, Samson Mataraso, Anna Siefkas, Gregory Braden, R. Phillip Dellinger, Andrea McCoy, Jean-Louis Vincent, Abigail Green-Saxena, Gina Barnes, Jana Hoffman, Jacob Calvert, Emily Pellegrini, Ritankar Das
Abstract Background Currently, physicians are limited in their ability to provide an accurate prognosis for COVID-19 positive patients. Existing scoring systems have been ineffective for identifying patient decompensation. Machine learning (ML) may offer an alternative strategy. A prospectively validated method to predict the need for ventilation in COVID-19 patients is essential to help triage patients, allocate resources, and prevent emergency intubations and their associated risks. Methods In a multicenter clinical trial, we evaluated the performance of a machine learning algorithm for prediction of invasive mechanical ventilation of COVID-19 patients within 24 h of an initial encounter. We enrolled patients with a COVID-19 diagnosis who were admitted to five United States health systems between March 24 and May 4, 2020. Results 197 patients were enrolled in the REspirAtory Decompensation and model for the triage of covid-19 patients: a prospective studY (READY) clinical trial. The algorithm had a higher diagnostic odds ratio (DOR, 12.58) for predicting ventilation than a comparator early warning system, the Modified Early Warning Score (MEWS). The algorithm also achieved significantly higher sensitivity (0.90) than MEWS, which achieved a sensitivity of 0.78, while maintaining a higher specificity (p < 0.05). Conclusions In the first clinical trial of a machine learning algorithm for ventilation needs among COVID-19 patients, the algorithm demonstrated accurate prediction of the need for mechanical ventilation within 24 h. This algorithm may help care teams effectively triage patients and allocate resources. Further, the algorithm is capable of accurately identifying 16% more patients than a widely used scoring system while minimizing false positive results.
Authors Francesca Pizzolo, Anna Maria Rigoni, Sergio De Marchi, Simonetta Friso, Elisa Tinazzi, Giulia Sartori, Filippo Stefanoni, Francesca Nalin, Martina Montagnana, Sara Pilotto, Michele Milella, Anna Maria Azzini, Evelina Tacconelli, Giacomo Marchi, Domenico Girelli, Oliviero Olivieri, Nicola Martinelli
Authors Hélène Péréa, Benoit Védied, Raphaël Vernete, Nathalie Demoryf, Najiby Kassisg, Tristan Miraultb, Hélène Lazarethi, Geoffroy Vollej, Elsa Denoixj, David Lebeauxc, Isabelle Podglajenc, Laurent Béleca, David Veyera
ABSTRACT Facing the ongoing pandemic caused by SARS-CoV-2, there is an urgent need for serological assays identifying individuals with on-going infection as well as past coronavirus infectious disease 2019 (COVID-19). We herein evaluated the analytical performances of the CE IVD-labeled Abbott SARS-CoV-2 IgG assay (Des Plaines, IL, USA) carried out with the automated Abbott Architect™ i2000 platform at Hôpital Européen Georges Pompidou, Paris, France, using serum sample panels obtained from health-workers with COVID-19 history confirmed by positive nucleic acid amplification-based diagnosis and from patients randomly selected for whom serum samples were collected before the COVID-19 epidemic. The Abbott SARS-CoV-2 IgG assay showed sensitivity of 94 % and specificity of 100 %, demonstrating high analytical performances allowing convenient management of suspected on-going and past-infections. In addition, the SARS-CoV-2 IgG positivity rates were compared in COVID-19 positive and COVID-19 free areas from our hospital. Thus, the frequency of SARS-CoV-2-specific IgG was around 10-fold higher in COVID-19 areas than COVID-19 free areas (75 % versus 8%; P < 0.001). Interestingly, several inpatients hospitalized in COVID-19 free areas suffering from a wide range of unexplained clinical features including cardiac, vascular, renal, metabolic and infectious disorders, were unexpectedly found seropositive for SARS-CoV-2 IgG by systematic routine serology, suggesting possible causal involvement of SARS-CoV-2 infection. Taken together, these observations highlight the potential interest of SARS-CoV-2-specific serology in the context of COVID-19 epidemic, especially to assess past SARS-CoV-2 infection as well as possible unexpected COVID-19-associated disorders.
ABSTRACT Background and aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in- hospital death. Methods and results: Retrospective observational study on 3,894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In- hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR=4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥90 mL/min/1.73m2 ; HR=2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.
Authors Michele Bartoletti, Renato Pascale, Monica Cricca, Matteo Rinaldi, Angelo Maccaro, Linda Bussini, Giacomo Fornaro, Tommaso Tonetti, Giacinto Pizzilli, Eugenia Francalanci, Lorenzo Giuntoli, Arianna Rubin, Alessandra Moroni, Simone Ambretti, Filippo Trapani, Oana Vatamanu, Vito Marco Ranieri, Andrea Castelli, Massimo Baiocchi, Russell Lewis, Maddalena Giannella, Pierluigi Viale
ABSTRACT Background In this study we evaluated the incidence of invasive pulmonary aspergillosis among intubated patients with critical coronavirus disease 2019 (COVID-19) and evaluated different case definitions of invasive aspergillosis. Methods Prospective, multicentre study on adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation. All included participants underwent screening protocol for invasive pulmonary aspergillosis with bronchoalveolar lavage galactomannan and cultures performed on admission at 7 days and in case of clinical deterioration. Cases were classified as coronavirus associated pulmonary aspergillosis (CAPA) according to previous consensus definitions. The new definition was compared with putative invasive pulmonary aspergillosis (PIPA). Results A total of 108 patients were enrolled. Probable CAPA was diagnosed in 30 (27.7%) of patients after a median of 4 (2-8) days from intensive care unit (ICU) admission. Kaplan-Meier curves showed a significant higher 30-day mortality rate from ICU admission among patients with either CAPA (44% vs 19%, p= 0.002) or PIPA (74% vs 26%, p<0.001) when compared with patients not fulfilling criteria for aspergillosis. The association between CAPA [OR 3.53 (95%CI 1.29-9.67), P=0.014] or PIPA [OR 11.60 (95%CI 3.24-41.29) p<0.001] with 30-day mortality from ICU admission was confirmed even after adjustment for confounders with a logistic regression model. Among patients with CAPA receiving voriconazole treatment (13 patients, 43%) A trend toward lower mortality (46% vs 59% p=0.30) and reduction of galactomannan index in consecutive samples was observed. Conclusion We found a high incidence of CAPA among critically ill COVID-19 patients and that its occurrence seems to change the natural history of disease
NEJM
Authors Wendy S. Armstrong
Authors Valentina O. Puntmann, M. Ludovica Carerj, Imke Wieters, Masia Fahim; Christophe Arendt, Jedrzej Hoffmann, Anastasia Shchendrygina, Felicitas Escher, Mariuca Vasa-Nicotera, Andreas M. Zeiher, Maria Vehreschild, Eike Nagel
ABSTRACT Importance Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. Objective To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness. Design, Setting, and Participants In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020. Exposure Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract. Main Outcomes and Measures Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57). Results Of the 100 included patients, 53 (53%) were male, and the median (interquartile range [IQR]) age was 49 (45-53) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (3 pg/mL or greater) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (13.9 pg/mL or greater) in 5 patients (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, higher left ventricle mass, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), and pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1122 [1113-1132] ms vs 1143 [1131-1156] ms; P = .02) but not for native T2 mapping or hsTnT levels. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.35; P < .001) and native T2 mapping (r = 0.22; P = .03). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19–related myocardial pathology. Conclusions and Relevance In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
Authors Diana Lindner, Antonia Fitzek, Hanna Bräuninger, Ganna Aleshcheva, Caroline Edler, Kira Meissner; Katharina Scherschel, Paulus Kirchhof, Felicitas Escher, Heinz-Peter Schultheiss, Stefan Blankenberg, Klaus Püschel, Dirk Westermann
ABSTRACT Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown. Objective To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection. Design, Setting, and Participants This cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests. Exposures Patients who died of coronavirus disease 2019. Main Outcomes and Measures Incidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3+, CD45+, and CD68+ cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18. Results Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field. Conclusions and Relevance In this analysis of autopsy cases, viral presence within the myocardium could be documented. While a response to this infection could be reported in cases with higher virus load vs no virus infection, this was not associated with an influx of inflammatory cells. Future investigations should focus on evaluating the long-term consequences of this cardiac involvement.
Authors Rafael Bellotti Azevedo, Bruna Gopp Botelho, João Victor Gonçalves de Hollanda, Leonardo Villa Leão Ferreira, Letícia Zarur Junqueira de Andrade, Stephanie Si Min Lilienwald Oei, Tomás de Souza Mello, Elizabeth Silaid Muxfeldt
ABSTRACT Cardiac injury in patients infected with the novel Coronavirus (COVID-19) seems to be associated with higher morbimortality. We provide a broad review of the clinical evolution of COVID-19, emphasizing its impact and implications on the cardiovascular system. The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by overproduction of inflammatory cytokines (IL-6 and TNF-α) leading to systemic inflammation and multiple organ dysfunction syndrome, acutely affecting the cardiovascular system. Hypertension (56.6%) and diabetes (33.8%) are the most prevalent comorbidities among individuals with COVID-19, who require hospitalization. Furthermore, cardiac injury, defined as elevated us-troponin I, significantly relates to inflammation biomarkers (IL-6 and C-reactive protein (CRP), hyperferritinemia, and leukocytosis), portraying an important correlation between myocardial injury and inflammatory hyperactivity triggered by viral infection. Increased risk for myocardial infarction, fulminant myocarditis rapidly evolving with depressed systolic left ventricle function, arrhythmias, venous thromboembolism, and cardiomyopathies mimicking STEMI presentations are the most prevalent cardiovascular complications described in patients with COVID-19. Moreover, SARS-CoV-2 tropism and interaction with the RAAS system, through ACE2 receptor, possibly enhances inflammation response and cardiac aggression, leading to imperative concerns about the use of ACEi and ARBs in infected patients. Cardiovascular implications result in a worse prognosis in patients with COVID-19, emphasizing the importance of precocious detection and implementation of optimal therapeutic strategies.
Authors Mohamed Nakeshbandi, Rohan Maini, Pia Daniel, Sabrina Rosengarten, Priyanka Parmar, Clara Wilson, Julie Minjae Kim, Alvin Oommen, Max Mecklenburg, Jerome Salvani, Michael A. Joseph, Igal Breitman
ABSTRACT ackground Obesity is an epidemic in New York City, the global epicenter of the coronavirus pandemic. Previous studies suggest that obesity is a possible risk factor for adverse outcomes in COVID-19. Objective To elucidate the association between obesity and COVID-19 outcomes. Design Retrospective cohort study of COVID-19 hospitalized patients tested between March 10 and April 13, 2020. Setting SUNY Downstate Health Sciences University, a COVID-only hospital in New York. Participants In total, 684 patients were tested for COVID-19 and 504 were analyzed. Patients were categorized into three groups by BMI: normal (BMI 18.50–24.99), overweight (BMI 25.00–29.99), and obese (BMI ≥ 30.00). Measurements Primary outcome was 30-day in-hospital mortality, and secondary outcomes were intubation, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute cardiac injury (ACI). Results There were 139 patients (27%) with normal BMI, 150 patients who were overweight (30%), and 215 patients with obesity (43%). After controlling for age, gender, diabetes, hypertension, and qSOFA score, there was a significantly increased risk of mortality in the overweight (RR 1.4, 95% CI 1.1–1.9) and obese groups (RR 1.3, 95% CI 1.0–1.7) compared with those with normal BMI. Similarly, there was a significantly increased relative risk for intubation in the overweight (RR 2.0, 95% CI 1.2–3.3) and obese groups (RR 2.4, 95% CI 1.5–4.0) compared with those with normal BMI. Obesity did not affect rates of AKI, ACI, or ARDS. Furthermore, obesity appears to significantly increase the risk of mortality in males (RR 1.4, 95% CI 1.0-2.0, P = 0.03), but not in females (RR 1.2, 95% CI 0.77–1.9, P = 0.40). Conclusion This study reveals that patients with overweight and obesity who have COVID-19 are at increased risk for mortality and intubation compared to those with normal BMI. These findings support the hypothesis that obesity is a risk factor for COVID-19 complications and should be a consideration in management of COVID-19.
Authors Quarraisha Abdool Karim, Salim S. Abdool Karim
AMERICAN SOCIETY FOR MICROBIOLOGY
Authors Jorge Sepulveda, Lars F. Westblade, Susan Whittier, Michael J. Satlin, William G. Greendyke, Justin G. Aaron, Jason Zucker, Donald Dietz, Magdalena Sobieszczyk, Justin J. Choi, Dakai Liu, Sarah Russell, Charles Connelly, Daniel A. Green
ABSTRACT A surge of patients with coronavirus disease 2019 (COVID-19) present- ing to New York City hospitals in March 2020 led to a sharp increase in blood cul- ture utilization, which overwhelmed the capacity of automated blood culture instru- ments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia and to inform a diagnostic approach to relieve blood culture overutiliza- tion. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evalu- ate order volume, positivity rate, time to positivity, and etiologies of positive cul- tures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the level in the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than among COVID-19-negative patients (8.0%) and those not tested (7.1%) (P 0.001). COVID-19 patients had a high proportion of organisms reflective of commensal skin microbiota, which, when excluded, reduced the bacteremia rate to 1.6%. More than 98% of all positive cul- tures were detected within 4 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the judicious use of blood cultures in the ab- sence of compelling evidence for bacterial coinfection. Clear communication with or- dering providers is necessary to prevent overutilization of blood cultures during pa- tient surges, and laboratories should consider shortening the incubation period from 5 days to 4 days, if necessary, to free additional capacity.
Authors Michail I. Papafaklis, Christos S. Katsouras, Grigorios Tsigkas, Konstantinos Toutouzas, Periklis Davlouros, George N. Hahalis, Maria S. Kousta, Ioannis G. Styliadis, Konstantinos Triantafyllou, Loukas Pappas, Fotini Tsiourantani, Efthymia Varytimiadi, Zacharias‐Alexandros Anyfantakis, Nikolaos Iakovis. Paraskevi Grammata, Haralambos Karvounis, Antonios Ziakas, George Sianos, Dimitrios Tziakas, Evgenia Pappa, Anna Dagre, Sotirios Patsilinakos, Athanasios Trikas, Thomais Lamprou, Ioannis Mamarelis, Georgios Katsimagklis, Dimitri Karmpaliotis, Katerina Naka, Lampros K. Michalis
ABSTRACT Background Reports from countries severely hit by the COVID‐19 pandemic suggest a decline in acute coronary syndrome (ACS)‐related hospitalizations. The generalizability of this observation on ACS admissions and possible related causes in countries with low COVID‐19 incidence are not known. Hypothesis ACS admissions were reduced in a country spared by COVID‐19. Methods We conducted a nationwide study on the incidence rates of ACS‐related admissions during a 6‐week period of the COVID‐19 outbreak and the corresponding control period in 2019 in Greece, a country with strict social measures, low COVID‐19 incidence, and no excess in mortality. Results ACS admissions in the COVID‐19 (n = 771) compared with the control (n = 1077) period were reduced overall (incidence rate ratio [IRR]: 0.72, P < .001) and for each ACS type (ST‐segment elevation myocardial infarction [STEMI]: IRR: 0.76, P = .001; non‐STEMI: IRR: 0.74, P < .001; and unstable angina [UA]: IRR: 0.63, P = .002). The decrease in STEMI admissions was stable throughout the COVID‐19 period (temporal correlation; R2 = 0.11, P = .53), whereas there was a gradual decline in non‐STEMI/UA admissions (R2 = 0.75, P = .026) following the progressively stricter social measures. During the COVID‐19 period, patients admitted with ACS presented more frequently with left ventricular systolic impairment (22.2 vs 15.5% control period; P < .001). Conclusions We observed a reduction in ACS hospitalizations during the COVID‐19 outbreak in a country with strict social measures, low community transmission, and no excess in mortality. Medical care avoidance behavior is an important factor for these observations, while a true reduction of the ACS incidence due to self‐isolation/quarantining may have also played a role.
Authors Sharon E. Fox, Guang Li, Aibek Akmatbekov, Jack L. Harbert, Fernanda S. Lameira, J. Quincy Brown, Richard S. Vander Heide
Authors Jacqui Wise
Authors Bo Yuan, Han-Qing Liu, Zheng-Rong Yang, Yong-Xin Chen, Zhi-Yong Liu, Kai Zhang, Cheng Wang, Wei-Xin Li, Ya-Wen An, Jian-Chun Wang, Shuo Song
ABSTRACT Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients is receiving more attention. Herein we report a cohort study on the follow-up of 182 recovered patients under medical isolation observation. Twenty (10.99%) patients out of the 182 were detected to be SARS-CoV-2 RNA positive (re-positives), although none showed any clinical symptomatic recurrence, indicating that COVID-19 responds well to treatment. Patients aged under 18 years had higher re-positive rates than average, and none of the severely ill patients re-tested positive. There were no significant differences in sex between re-positives and non-re-positives. Notably, most of the re-positives turned negative in the following tests, and all of them carried antibodies against SARS-CoV-2. This indicates that they might not be infectious, although it is still important to perform regular SARS-CoV-2 RNA testing and follow-up for assessment of infectivity. The findings of this study provide information for improving the management of recovered patients, and for differentiating the follow-up of recovered patients with different risk levels.
Authors Matteo Apicella, Maria Cristina Campopiano, Michele Mantuano, Laura Mazoni, Alberto Coppelli, Stefano Del Prato
CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)
Authors Nakwon Kwak, Seung-Sik Hwang, and Jae-Joon Yim
ABSTRACT After South Korea raised its infectious disease alert to the highest level in response to coronavirus disease emergence, tuberculosis notification during the first 18 weeks of 2020 decreased significantly from the same period for each year during 2015–2019. Adequate measures to diagnose, control, and prevent tuberculosis need to be maintained.
Authors Roberta Della Bona, Alberto Valbusa, Giovanni La Malfa, Daniele Roberto Giacobbe, Pietro Ameri, Niccolò Patroniti, Chiara Robba, Vered Gilad, Angelo Insorsi, Matteo Bassetti, Paolo Pelosi, Italo Porto
Authors Matteo Cameli, Maria Concetta Pastore, Hatem Soliman Aboumarie, Giulia Elena Mandoli, Flavio D'Ascenzi, Paolo Cameli ,Elisa Bigio, Federico Franchi, Sergio Mondillo, Serafina Valente
ABSTRACT Coronavirus disease 2019 (COVID‐19) outbreak is a current global healthcare burden, leading to the life‐threatening severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, evidence showed that, even if the prevalence of COVID‐19 damage consists in pulmonary lesions and symptoms, it could also affect other organs, such as heart, liver, and spleen. Particularly, some infected patients refer to the emergency department for cardiovascular symptoms, and around 10% of COVID‐19 victims had finally developed heart injury. Therefore, the use of echocardiography, according to the safety local protocols and ensuring the use of personal protective equipment, could be useful firstly to discriminate between primary cardiac disease or COVID‐19–related myocardial damage, and then for assessing and monitoring COVID‐19 cardiovascular complications: acute myocarditis and arrhythmias, acute heart failure, sepsis‐induced myocardial impairment, and right ventricular failure derived from treatment with high‐pressure mechanical ventilation. The present review aims to enlighten the applications of transthoracic echocardiography for the diagnostic and therapeutic management of myocardial damage in COVID‐19 patients.
Authors Marco Marietta, Valeria Coluccio, Mario Luppi
ABSTRACT The acute respiratory illnesses caused by severe acquired respiratory syndrome corona Virus-2 (SARS-CoV-2) is a global health emergency, involving more than 8.6 million people worldwide with more than 450,000 deaths. Among the clinical manifestations of COVID-19, the disease that results from SARS-CoV-2 infection in humans, a prominent feature is a pro-thrombotic derangement of the hemostatic system, possibly representing a peculiar clinicopathologic manifestation of viral sepsis. The severity of the derangement of coagulation parameters in COVID-19 patients has been associated with a poor prognosis, and the use of low molecular weight heparin (LMWH) at doses registered for prevention of venous thromboembolism (VTE) has been endorsed by the World Health Organization and by Several Scientific societies. However, some relevant issues on the relationships between COVID-19, coagulopathy and VTE have yet to be fully elucidated. This review is particularly focused on four clinical questions: What is the incidence of VTE in COVID-19 patients? How do we frame the COVID-19 associated coagulopathy? Which role, if any, do antiphospolipid antibodies have? How do we tackle COVID-19 coagulopathy? In the complex scenario of an overwhelming pandemic, most everyday clinical decisions have to be taken without delay, although not yet supported by a sound scientific evidence. This review discusses the most recent findings of basic and clinical research about the COVID-associated coagulopathy, to foster a more thorough knowledge of the mechanisms underlying this compelling disease.
JMIR PUBLICATION
Authors Fulvio Adorni, Federica Prinelli, Fabrizio Bianchi, Andrea Giacomelli, Gabriele Pagani, Dario Bernacchia, Stefano Rusconi, Stefania Maggi, Caterina Trevisan, Marianna Noale, Sabrina Molinaro, Luca Bastiani, Loredana Fortunato, Nithiya Jesuthasan, Aleksandra Sojic, Carla Pettenati, Marcello Tavio, Massimo Andreoni, Claudio Mastroianni, Raffaele Antonelli Incalzi, Massimo Galli
ABSTRACT Background: Understanding the occurrence of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)-like symptoms in a large non-hospitalized population, when the epidemic peak was occurring in Italy, is of paramount importance but data are scarce. Objective: Aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test in non-hospitalized individuals and to estimate the occurrence of COVID-19-like symptoms in a larger non-tested population. Methods: This is an Italian countrywide self-administered cross-sectional web-based survey on voluntary adults who completed an anonymous questionnaire in the period 13-21 April 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios with 95% confidence intervals (aOR, 95%CI) by means of multiple logistic regression analysis controlling for age, sex, education, smoking habits, and the number of co-morbidities. Thereafter, for each symptom and for their combination, we calculated sensitivity, specificity, accuracy and AUC in a ROC analysis to estimate the occurrence of COVID-19-like infections in the non-tested population. Results: A total of 171,310 responded to the survey (59.9% females, mean age 47.4 years). Out of the 4,785 respondents with known NPS test result, 4,392 were not hospitalized. Among them, the NPS positive respondents (n=856) most frequently reported myalgia (61.6%), olfactory and/or taste disorders (OTDs, 59.2%), cough (54.4%), and fever (51.9%) whereas 7.7% were asymptomatic. Multiple regression analysis showed that OTDs (aOR 10.3, [95%CI 8.4-12.7]), fever (2.5, 95%CI 2.0-3.1), myalgia (1.5, 95%CI 1.2-1.8), and cough (1.3, 95%CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95%CI, 5.6-9.7) to 35.5 (95%CI, 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95%CI 0.795-0.825) in classifying NPS-P, and was applied to the non-hospitalized and non-tested sample (n=165,782). We found that from 4.4% to 12.1% of respondents had experienced symptoms suggestive of COVID-19 infection. Conclusions: Our results suggest that self-reported symptoms may be reliable indicators of SARS-CoV-2 infection in a pandemic context. A not negligible part (up to 12.1%) of the symptomatic respondents were left undiagnosed and potentially contributed to the spread of the infection.
Authors Danying Liao, Fen Zhou, Lili Luo, Min Xu, Hongbo Wang, Jiahong Xia, Yong Gao, Liqiong Cai, Zhihui Wang, Ping Yin, Yadan Wang, Lu Tang, Jun Deng, Heng Mei†, Yu Hu
Authors Patrick Davies, Claire Evans, Hari Krishnan Kanthimathinathan, Jon Lillie, Joseph Brierley, Gareth Waters, Mae Johnson, Benedict Griffiths, Pascale du Pré, Zoha Mohammad, Akash Deep, Stephen Playfor, Davinder Singh, David Inwald, Michelle Jardine, Oliver Ross, Nayan Shetty, Mark Worrall, Ruchi Sinha, Ashwani Koul, Elizabeth Whittaker, Harish Vyas, Barnaby R Scholefield*, Padmanabhan Ramnarayan
Authors S Le Brocq, K Clare, M Bryant, K Roberts, AA Tahrani
Authors Giuseppe Ferrante, Fabio Fazzari, Ottavia Cozzi, Matteo Maurina, Renato Bragato, Federico D’Orazio, Chiara Torrisi, Ezio Lanza, Eleonora Indolfi, Valeria Donghi, Riccardo Mantovani, Gaetano Liccardo, Antonio Voza, Elena Azzolini,, Luca Balzarini, Bernhard Reimers, Giulio G Stefanini, Gianluigi Condorelli, Lorenzo Monti
ABSTRACT Aims Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19. Methods and Results This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I > 20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th–75th percentile, 27–32) mm vs. 27.7 (25–30) mm, < 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02–1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02–1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, < 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27–3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO/FiO ratio on admission were other independent predictors for both myocardial injury and death. Conclusions An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death.
Authors A. Cingolani, A. M. Tummolo, G. Montemurro, E. Gremese, L. Larosa, M. C. Cipriani, G. Pasciuto, R. Liperoti, R. Murri, T. Pirronti, R. Cauda, M. Fantoni
ABSTRACT A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.
Authors Betty Y. Yang, Leslie M. Barnard, Jamie M. Emert, Christopher Drucker, Leilani Schwarcz, Catherine R. Counts, David L. Murphy, Sally Guan, Kosuke Kume, Karen Rodriquez, Tracie Jacinto, Susanne May, Michael R. Sayre, Thomas Rea
ABSTRACT Importance The ability to identify patients with coronavirus disease 2019 (COVID-19) in the prehospital emergency setting could inform strategies for infection control and use of personal protective equipment. However, little is known about the presentation of patients with COVID-19 requiring emergency care, particularly those who used 911 emergency medical services (EMS). Objective To describe patient characteristics and prehospital presentation of patients with COVID-19 cared for by EMS. Design, Setting, and Participants This retrospective cohort study included 124 patients who required 911 EMS care for COVID-19 in King County, Washington, a large metropolitan region covering 2300 square miles with 2.2 million residents in urban, suburban, and rural areas, between February 1, 2020, and March 18, 2020. Exposures COVID-19 was diagnosed by reverse transcription–polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swabs. Test results were available a median (interquartile range) of 5 (3-9) days after the EMS encounter. Main Outcomes and Measures Prevalence of clinical characteristics, symptoms, examination signs, and EMS impression and care. Results Of the 775 confirmed COVID-19 cases in King County, EMS responded to 124 (16.0%), with a total of 147 unique 911 encounters. The mean (SD) age was 75.7 (13.2) years, 66 patients (53.2%) were women, 47 patients (37.9%) had 3 or more chronic health conditions, and 57 patients (46.0%) resided in a long-term care facility. Based on EMS evaluation, 43 of 147 encounters (29.3%) had no symptoms of fever, cough, or shortness of breath. Based on individual examination findings, fever, tachypnea, or hypoxia were only present in a limited portion of cases, as follows: 43 of 84 encounters (51.2%), 42 of 131 (32.1%), and 60 of 112 (53.6%), respectively. Advanced care was typically not required, although in 24 encounters (16.3%), patients received care associated with aerosol-generating procedures. As of June 1, 2020, mortality among the study cohort was 52.4% (65 patients). Conclusions and Relevance The findings of this cohort study suggest that screening based on conventional COVID-19 symptoms or corresponding examination findings of febrile respiratory illness may not possess the necessary sensitivity for early diagnostic suspicion, at least in the prehospital emergency setting. The findings have potential implications for early identification of COVID-19 and effective strategies to mitigate infectious risk during emergency care.
Authors Denise Ignatowski, Sandra Zemke, Abby Payne, Bijoy K. Khandheria
Authors Jyoti Upadhyay, Nidhi Tiwari, Mohd N Ansari Mohd N Ansari
ABSTRACT The whole world is locked down due to the outbreak of novel Coronavirus Disease 2019 (nCOVID-19). A novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus pandemic 2019. Investigating the role of inflammatory mediators and understanding the virology of nCOVID-19 virus help in designing a rational and effective therapy for this infection. This review provides an overview of the inflammatory mediators activated during nCOVID-19 infection and the pathophysiology of this viral infection. In this review, the authors have a detailed discussion about the types of viral strains of nCOVID-19, its mechanism of action, host immune response, and the dysregulation caused by the viruses in the host immune system causing disease progression. Understanding the role of inflammatory cytokines, chemokines, and clinical immunology will be the approach to find out the possible novel therapeutic interventions. Therapies involving regulation of immune responses help in inhibiting the various steps in the pathologies of infection. Also, updated knowledge regarding the dysregulation of immune system and disease outcome in critically ill patients serves as a precautionary measure in the development and evaluation of vaccine.
Authors Angelo Santoliquido, Angelo Porfidia, Antonio Nesci, Giuseppe De Matteis, Giuseppe Marrone, Enrica Porceddu, Giulia Cammà, Igor Giarretta, Massimo Fantoni, Francesco Landi, Antonio Gasbarrini, Roberto Pola
ABSTRACT Background A remarkably high incidence of VTE has been reported among critically ill patients with COVID‐19 assisted in the Intensive Care Unit (ICU). However, VTE burden among non‐ICU patients hospitalized for COVID‐19 that receive guideline‐recommended thromboprophylaxis is unknown. Objectives To determine the incidence of VTE among non‐ICU patients hospitalized for COVID‐19 that receive pharmacological thromboprophylaxis. Methods We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non‐ICU patients hospitalized for COVID‐19, independently of the presence of signs or symptoms of DVT. All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux. Results The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6±13.5 years and a mean Padua Prediction Score of 5.1±1.6. Seventy‐two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden. In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% CI 4.98–18.82). Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI ‐0.87–5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23–5.77). Significant differences between subjects with and without DVT were D‐dimer >3,000 µg/L (P<0.05), current or previous cancer (P<0.05), and need of high flow nasal oxygen therapy and/or non‐invasive ventilation (P<0.01). Conclusions DVT may occur among non‐ICU patients hospitalized for COVID‐19, despite guideline‐recommended thromboprophylaxis.
Authors Jixin Zhong, Guifen Shen, Huiqin Yang, Anbin Huang, Xiaoqi Chen, Li Dong, Bin Wu, Anbin Zhang, Linchong Su, Xiaoqiang Hou, Shulin Song, Huiling Li, Wenyu Zhou, Tao Zhou, Qin Huang, Aichun Chu, Zachary Braunstein, Xiaoquan Rao, Cong Ye, Lingli Dong
Authors Arnar Breevoort, Giovanni A. Carosso, Mohammed A. Mostajo-Radji
Authors Kimon V. Argyropoulos, Antonio Serrano, Jiyuan Hu,y Margaret Black, Xiaojun Feng, Guomiao Shen, Melissa Call,z Min J. Kim,z Andrew Lytle, Brendan Belovarac, Theodore Vougiouklakis, Lawrence H. Lin, Una Moran, Adriana Heguy, Andrea Troxel, Matija Snuderl, Iman Osman, Paolo Cotzia, George Jour
Authors Naim Ouldali, Marie Pouletty, Patricia Mariani, Constance Beyler, Audrey Blachier, Stephane Bonacorsi, Kostas Danis, Maryline Chomton, Laure Maurice, Fleur Le Bourgeois, Marion Caseris, Jean Gaschignard, Julie Poline, Robert Cohen, Luigi Titomanlio, Albert Faye, Isabelle Melki, Ulrich Meinzer
PEDIATRICS
Authors Mariateresa Sinelli, Giuseppe Paterlini, Marco Citterio, Alessia Di Marco, Tiziana Fedeli and Maria Luisa Ventura
ABSTRACT We describe a case of neonatal SARS-CoV-2 infection, in an infant diagnosed 3 days after birth, and manifesting with silent hypoxemia, requiring respiratory support. Abbreviations: COVID-19 — coronavirus disease PCR — polymerase chain reaction SARS-CoV-2 — severe acute respiratory syndrome coronavirus 2 In December 2019, an emergent new coronavirus was detected in Wuhan, China, as the cause of severe pneumonia.1 The virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a disease named coronavirus disease (COVID-19) and has become a pandemic.2 At the end of February, a cluster of cases was identified in Northern Italy. Since then, SARS-CoV-2 has been responsible for more than 80 000 infections among Italian adults, with ∼10 neonatal cases detected. The disease seems to be mild in children and, to date, there are few reports in neonatal population. It is still not clear if there is vertical transmission of virus from mother to newborn and there is not a consensus on the appropriate infection control precautions to be used in the care of the newborn. We report a case of COVID-19 infection in a term newborn who required respiratory support after a vaginal delivery.
CRITICAL CARE AND RESUSCITATION
Authors Alberto Zangrillo, Luigi Beretta, Anna Mara Scandroglio, Giacomo Monti, Evgeny Fominskiy, Sergio Colombo, Federica Morselli, Alessandro Belletti, Paolo Silvani, Martina Crivellari, Fabrizio Monaco, Maria Luisa Azzolini, Raffaella Reineke, Pasquale Nardelli, Marianna Sartorelli, Carmine D Votta, Annalisa Ruggeri, Fabio Ciceri, Francesco De Cobelli, More- no Tresoldi, Lorenzo Dagna, Patrizia Rovere-Querini, Ary Serpa Neto, Rinaldo Bellomo, Giovanni Landoni
ABSTRACT Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3 ; IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL; IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 μg/m; IQR, 5.0-23.8 μg/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12; 95% CI, 1.04-1.22; P = 0.004) and hypertension (OR, 6.15; 95% CI, 1.75-29.11; P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors.
Authors Takahisa Mikami, Hirotaka Miyashita, Takayuki Yamada, Matthew Harrington, Daniel Steinberg, Andrew Dunn, Evan Siau
ABSTRACT Background New York City emerged as an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Objective To describe the clinical characteristics and risk factors associated with mortality in a large patient population in the USA. Design Retrospective cohort study. Participants 6493 patients who had laboratory-confirmed COVID-19 with clinical outcomes between March 13 and April 17, 2020, who were seen in one of the 8 hospitals and/or over 400 ambulatory practices in the New York City metropolitan area Main Measures Clinical characteristics and risk factors associated with in-hospital mortality. Key Results A total of 858 of 6493 (13.2%) patients in our total cohort died: 52/2785 (1.9%) ambulatory patients and 806/3708 (21.7%) hospitalized patients. Cox proportional hazard regression modeling showed an increased risk of in-hospital mortality associated with age older than 50 years (hazard ratio [HR] 2.34, CI 1.47–3.71), systolic blood pressure less than 90 mmHg (HR 1.38, CI 1.06–1.80), a respiratory rate greater than 24 per min (HR 1.43, CI 1.13–1.83), peripheral oxygen saturation less than 92% (HR 2.12, CI 1.56–2.88), estimated glomerular filtration rate less than 60 mL/min/1.73m2 (HR 1.80, CI 1.60–2.02), IL-6 greater than 100 pg/mL (HR 1.50, CI 1.12–2.03), D-dimer greater than 2 mcg/mL (HR 1.19, CI 1.02–1.39), and troponin greater than 0.03 ng/mL (HR 1.40, CI 1.23–1.62). Decreased risk of in-hospital mortality was associated with female sex (HR 0.84, CI 0.77–0.90), African American race (HR 0.78 CI 0.65–0.95), and hydroxychloroquine use (HR 0.53, CI 0.41–0.67). Conclusions Among patients with COVID-19, older age, male sex, hypotension, tachypnea, hypoxia, impaired renal function, elevated D-dimer, and elevated troponin were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality.
Authors Ying Wang, Li Shi, Yadong Wang, Guangcai Duan, Haiyan Yang
Authors J. Mayol, C. Artucio, I. Batista, A. Puentes, J. Villegas, R Quizpe, V. Rojas, J. Mangione, J. Belardi
ABSTRACT Introduction A reduction in the number of interventional cardiology procedures has emerged as a result of the COVID-19 pandemic. A survey was performed to quantify this decrease and the impact on the management of myocardial infarction in Latin America. Methods A telematic survey was conducted for all countries in Latin America. Diagnostic catheterisations, coronary and structural interventions, as well as the incidence and delay to reperfusion therapy of myocardial infarction (STEMI), were recorded. Two periods were compared: from 24 February to 8 March 2020 (pre-COVID-19) and another 2‑week period that varied according to country (COVID-19). Results Responses were obtained from 79 centres in 20 countries. There was a significant decrease in the number of diagnostic procedures (−65.2%), coronary interventions (−59.4%), structural therapeutics (−86.1%) and STEMI care (−51.2%). A decrease was noted in the incidence of STEMI, but also a delay in the time to STEMI reperfusion. While there was a variation in activity in interventional cardiology between countries, patient behaviour was rather homogeneous. Conclusions A significant reduction in healthcare activity has been noted during the COVID-19 pandemic, including STEMI care, with the risk of increased mortality and/or morbidity following STEMI. Healthcare providers should encourage patients with suspected symptoms of STEMI to call for emergency care to ensure rapid diagnosis and timely reperfusion treatment. What’s new? A marked reduction in interventional cardiology activity has been observed in Latin America during the COVID-19 pandemic, both in elective and emergency procedures, particularly in patients with STEMI. In Latin America patient behaviour has been quite homogeneous, although varying quarantine measures in the individual countries have restricted mobility to different degrees. The health authorities should be alert regarding the care of STEMI patients during the COVID-19 pandemic.
Authors Jonathan Hewitt, Ben Carter, Arturo Vilches-Moraga, Terence J Quinn, Philip Braude, Alessia Verduri, Lyndsay Pearce, Michael Stechman, Roxanna Short, Angeline Price, Jemima T Collins, Eilidh Bruce, Alice Einarsson, Frances Rickard, Emma Mitchell, Mark Holloway, James Hesford, Fenella Barlow-Pay, Enrico Clini, Phyo K Myint, Susan J Moug, Kathryn McCarthy
Authors Noémi Zádori, Szilárd Váncsa, Nelli Farkas, Péter Hegyi, Bálint Erőss
Authors Marie Hauguel-Moreau, Rémy Pillière, Giulio Prati, Sébastien Beaune, Thomas Loeb, Simon Lannou, Sophie Mallet, Hazrije Mustafic, Céline Bégué, Olivier Dubourg, Nicolas Mansencal
ABSTRACT Data whether the COVID-19 outbreak impacts the acute coronary syndromes (ACS) admissions and the time required to reverse the downward curve are scarce. We included all consecutive patients referred for an ACS who underwent PCI from February 17, 2020 to April 26, 2020 in a high-volume PCI coronary care unit. We compared the number of ACS patients in 2020 to the same period in 2018 and 2019. Predictors of adverse outcome in ST-elevation myocardial infarction (STEMI) patients were recorded: symptom-onset-to-first medical contact (FMC), and FMC-to-sheath insertion times. During the studied period (calendar weeks 8–17, 2018–2020), 144 ACS patients were included. In 2020, we observed two distinct phases in the ACS admissions: a first significant fall, with a relative reduction of 73%, from the week of lockdown (week 12) to 3 weeks later and then an increase of ACS. Median symptom-onset-to-FMC time was significantly higher in 2020 than in the two previous years (600 min [298–632] versus 121 min [55–291], p < 0.001). Median FMC-to-sheath insertion did not differ significantly (93 min [81–131] in 2020 versus 90 min [67–137] in 2018–2019, p = 0.57). The main findings are (1) a pattern of a U-curve in ACS admissions, with a first decrease in ACS admissions and a return to “normality” 4 weeks after; (2) a significant increase in the total ischemic time exclusively due to an increase in the symptom-onset-to-first-medical-contact time.
Authors Yiying Huang, Cuiyan Tan, Jian Wu, Meizhu Chen, Zhenguo Wang, Liyun Luo, Xiaorong Zhou, Xinran Liu, Xiaoling Huang, Shican Yuan, Chaolin Chen, Fen Gao, Jin Huang, Hong Shan, Jing Liu
ABSTRACT Objective This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. Methods A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. Results Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p = 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. Conclusion Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.
Authors Leora R. Feldstein, Erica B. Rose, Steven M. Horwitz, Jennifer P. Collins, Margaret M. Newhams, Mary Beth F. Son, Jane W. Newburger, Lawrence C. Kleinman, Sabrina M. Heidemann, Amarilis A. Martin, Aalok R. Singh, Simon Li, Keiko M. Tarquinio, Preeti Jaggi, Matthew E. Oster, Sheemon P. Zackai, Jennifer Gillen, Adam J. Ratner Rowan F. Walsh, Julie C. Fitzgerald, Michael A. Keenaghan, Hussam Alharash, Sule Doymaz, Katharine N. Clouser, John S. Giuliano, Jr., Anjali Gupta, Robert M. Parker, Aline B. Maddux, Vinod Havalad, Stacy Ramsingh, Hulya Bukulmez, Tamara T. Bradford, Lincoln S. Smith, Mark W. Tenforde, Christopher L. Carroll, Becky J. Riggs, Shira J. Gertz, Ariel Daube, Amanda Lansell, Alvaro Coronado Munoz, Charlotte V. Hobbs, Kimberly L. Marohn, Natasha B. Halasa, Manish M. Patel, Adrienne G. Randolph
ABSTRACT BACKGROUND Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.)
Authors Elizabeth M. Dufort, Emilia H. Koumans, Eric J. Chow, Elizabeth M. Rosenthal, Alison Muse, Jemma Rowlands, Meredith A. Barranco,, Angela M. Maxted, Eli S. Rosenberg, Delia Easton, Tomoko Udo, Jessica Kumar, Wendy Pulver, Lou Smith, Brad Hutton, Debra Blog, Howard Zucker
ABSTRACT BACKGROUND A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019. The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome. METHODS Hospitals in New York State reported cases of Kawasaki’s disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH. We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020. RESULTS As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH. Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days. CONCLUSIONS The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.
Authors Michael Levin
ATM
Authors Chao Wang, Peiyu Huang, Lihua Wang, Zhujing Shen, Bin Lin, Qiyuan Wang, Tongtong Zhao, Hanpeng Zheng, Wenbin Ji, Yuantong Gao, Junli Xia, Jianmin Cheng, Jianbing Ma, Jun Liu, Yongqiang Liu, Miaoguang Su, Guixiang Ruan, Jiner Shu, Dawei Ren, Zhenhua Zhao, Weigen Yao, Yunjun Yang, Bo Liu, Minming Zhang
INTERNATIOANL JOURNAL OF STROKE
Authors Herbert Tejada Meza, Álvaro Lambea Gil, Agustín Sancho Saldaña, Maite Martínez-Zabaleta, Patricia de la Riva Juez, Elena López-Cancio Martínez, María Castañón Apilánez, María Herrera Isasi, Juan Marta Enguita, Mercedes de Lera Alfonso, Juan F Arenillas, Jon Segurola Olaizola, Juan José Timiraos Fernández, Joaquín Sánchez, Mar Castellanos-Rodrigo, Alexia Roel, Ignacio Casado Menéndez, Mar Freijo, Alain Luna Rodriguez, Enrique Palacio Portilla, Yésica Jiménez López, Emilio Rodríguez Castro, Susana Arias Rivas, Javier Tejada García, Iria Beltrán Rodríguez, Francisco Julián-Villaverde, Maria Pilar Moreno García, José María Trejo-Gabriel-Galán, Ana Echavarría Iñiguez, Carlos Tejero Juste, Cristina Pérez Lázaro, Javier Marta Moreno
ABSTRACT Background and purpose Spain has been one of the countries heavily stricken by COVID-19. But this epidemic has not affected all regions equally. We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain. Methods Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality. Results In the study period, 2737 patients were admitted with ischemic stroke. There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001). In-hospital mortality of stroke patients increased significantly (9.9% vs. 6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs. 16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504). Conclusion We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain. There were regional changes within the network, not fully explained by the severity of the pandemic in different regions.
Authors Ali A. Asadi-Pooya, Armin Attar, Mohsen Moghadami, Iman Karimzadeh
ABSTRACT People with epilepsy (PWE) are neither more likely to be infected by the coronavirus nor are they more likely to have severe COVID-19 manifestations because they suffer from epilepsy. However, management of COVID-19 in PWE may be more complicated than that in other individuals. Drug-drug interactions could pose significant challenges and cardiac, hepatic, or renal problems, which may happen in patients with severe COVID-19, may require adjustment to antiepileptic drugs (AEDs). In this review, we first summarize the potential drug-drug interactions between AEDs and drugs currently used in the management of COVID-19. We then summarize other challenging issues that may happen in PWE, who have COVID-19 and are receiving treatment.
Authors Fernando Sierra-Hidalgo, Nuria Muñoz-Rivas, Pedro Torres Rubio, Kateri Chao, Mercedes Villanova Martínez, Paz Arranz García, Eva Martínez-Acebes
TAYLOR & FRANCIS ONLINE
Authors Fabio Ciceri, Annalisa Ruggeri, Rosalba Lembo, Riccardo Puglisi, Giovanni Landoni, Alberto Zangrillo
Authors Florian Götzinger, Begoña Santiago-García, Antoni Noguera-Julián, Miguel Lanaspa, Laura Lancella, Francesca I Calò Carducci, Natalia Gabrovska, Svetlana Velizarova, Petra Prunk, Veronika Osterman, Uros Krivec, Andrea Lo Vecchio, Delane Shingadia, Antoni Soriano-Arandes, Susana Melendo, Marcello Lanari, Luca Pierantoni, Noémie Wagner, Arnaud G L’Huillier, Ulrich Heininger, Nicole Ritz, Srini Bandi, Nina Krajcar, Srđan Roglić, Mar Santos, Christelle Christiaens, Marine Creuven, Danilo Buonsenso, Steven B Welch, Matthias Bogyi, Folke Brinkmann, Marc Tebruegge,
Authors Juncal Roca-Ginés; Ignacio Torres-Navarro; Javier Sánchez-Arráez; Carlos Abril-Pérez; Oihana Sabalza-Baztán; Sergio Pardo-Granell, PharmG; Vicent Martínez i Cózar; Rafael Botella-Estrada; Montserrat Évole-Buselli
ABSTRACT Importance A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been identified as the cause of a pandemic called coronavirus disease 2019 (COVID-19). In this context, some associated skin diseases have been described. Cutaneous lesions referred to as acute acro-ischemia have been reported as a possible sign of COVID-19 in adolescents and children. Objective To evaluate the pathogenesis of these newly described acute acral lesions. Design, Setting, and Participants This prospective case series was conducted at La Fe University Hospital, a tertiary referral hospital in Valencia, Spain, between April 9 and April 15, 2020. Among 32 referred patients, 20 children and adolescents with new-onset inflammatory lesions did not have a diagnosis. Exposures Patients were not exposed to any drug or other intervention. Main Outcomes and Measures We performed reverse transcriptase–polymerase chain reaction for SARS-CoV-2 and a range of blood tests for possible origins of the lesions. Skin biopsies were performed in 6 patients. Results Of the 20 patients enrolled, 7 were female and 13 were male, with an age range of 1 to 18 years. Clinical findings fit into the following patterns: acral erythema (6 patients), dactylitis (4 patients), purpuric maculopapules (7 patients), and a mixed pattern (3 patients). None of the patients had remarkable hematologic or serologic abnormalities, including negative antibodies to SARS-CoV-2. Biopsies performed in 6 patients showed histologic findings characteristic of perniosis. Conclusions and Relevance The clinical, histologic, and laboratory test results were compatible with a diagnosis of perniosis, and no evidence was found to support the implication of SARS-CoV-2 infection.
Authors Aravinthan Varatharaj, Naomi Thomas, Mark A Ellul, Nicholas W S Davies, Thomas A Pollak, Elizabeth L Tenorio, Mustafa Sultan, Ava Easton, Gerome Breen, Michael Zandi, Jonathan P Coles, Hadi Manji, Rustam Al-Shahi Salman, David K Menon, Timothy R Nicholson, Laura A Benjamin, Alan Carson, Craig Smith, Martin R Turner, Tom Solomon, Rachel Kneen, Sarah L Pett, Ian Galea, Rhys H Thomas, Benedict D Michael
Authors Ozge Askin, Rozerin Neval Altunkalem, Dursun Dorukhan Altinisik, Tugba Kevser Uzuncakmak, Umit Tursen, Zekayi Kutlubay
ABSTRACT Background Cutaneous manifestations of COVID‐19 disease have not yet been fully described. Objectives To describe cutaneous manifestations of COVID‐19 disease in hospitalized patients. Methods We examined the cutaneous manifestations of 210 hospitalized patients. Results Cutaneous findings were observed during COVID‐19 infection in 52 of the patients. Lesions may be classified as erythematous scaly rash (32.7%), maculopapular rash (23%), urticarial lesions (13.5%), petechial purpuric rash (7.7%), necrosis (7.7%), enanthema and apthous stomatitis (5.8%), vesicular rash (5.8%), pernio (1.9%) and pruritus (1.9%). Cutaneous manifestations were observed statistically significantly more in certain age groups: patients of 55 to 64 and 65 to 74 years of age complained of more cutaneous manifestations than the other age groups. As for gender, there was no significant difference between male and female patients in terms of cutaneus findings. The relationship between comorbidity and dermatological finding status was statistically significant. The relationship increases linearly according to the comorbidities. According the statistical results the patients who were hospitalized in the intensive care unit had a higher risk of having cutaneous findings due to COVID‐19 infection. Conclusions With this study we may highlight the importance of overlooked dermatological findings in patients that are hospitalized.
Authors Sebastian Schnaubelt, Marie-Kathrin Breyer, Jolanta Siller-Matula, Hans Domanovits
ABSTRACT Background Fulminant cardiac involvement in COVID-19 patients has been reported; the underlying suspected mechanisms include myocarditis, arrhythmia, and cardiac tamponade. In parallel, atrial fibrillation is common in the elderly population which is at particularly high risk for COVID-19 morbidity and mortality. Case summary A 72-year-old male SARS-CoV2-positive patient was admitted to the intensive care unit due to delirium and acute respiratory failure. Atrial fibrillation known from history was exacerbated, and made complex rate and rhythm control necessary. Progressive heart failure with haemodynamic deterioration and acute kidney injury with the need for continuous renal replacement therapy were further aggravated by pericardial tamponade. Discussion Treatment of acute heart failure in COVID-19 patients with a cytokine storm complicated by tachycardic atrial fibrillation should include adequate rate or rhythm control, and potentially immunomodulation.
Authors Xiaofan Liu, Hong Zhou, Yilu Zhou, Xiaojun Wu, Yang Zhao, Yang Lu, Weijun Tan, Mingli Yuan, Xuhong Ding, Jinjing Zou, Ruiyun Li, Hailing Liu, Rob M. Ewing, Yi Hu, Hanxiang Nie & Yihua Wang
ABSTRACT COVID-19 is “public enemy number one” and has placed an enormous burden on health authorities across the world. Given the wide clinical spectrum of COVID-19, understanding the factors that can predict disease severity will be essential since this will help frontline clinical staff to stratify patients with increased confidence. To investigate the diagnostic value of the temporal radiographic changes, and the relationship to disease severity and viral clearance in COVID-19 patients. In this retrospective cohort study, we included 99 patients admitted to the Renmin Hospital of Wuhan University, with laboratory confirmed moderate or severe COVID-19. Temporal radiographic changes and viral clearance were explored using appropriate statistical methods. Radiographic features from HRCT scans included ground-glass opacity, consolidation, air bronchogram, nodular opacities and pleural effusion. The HRCT scores (peak) during disease course in COVID-19 patients with severe pneumonia (median: 24.5) were higher compared to those with pneumonia (median: 10) (p = 3.56 × 10 −12), with more frequency of consolidation (p = 0.025) and air bronchogram (p = 7.50 × 10−6). The median values of days when the peak HRCT scores were reached in pneumonia or severe pneumonia patients were 12 vs. 14, respectively (p = 0.048). Log-rank test and Spearman’s Rank-Order correlation suggested temporal radiographic changes as a valuable predictor for viral clearance. In addition, follow up CT scans from 11 pneumonia patients showed full recovery. Given the values of HRCT scores for both disease severity and viral clearance, a standardised HRCT score system for COVID-19 is highly demanded.
Authors Ying Zheng, Ling Wang, Suqin Ben
ABSTRACT Objectives To perform a meta‐analysis regarding the chest CT manifestations of COVID‐19 pneumonia patients. Methods PubMed, Embase and Cochrane Library databases were searched from December 1st 2019 until May 1st, 2020 using the keywords of ‘COVID‐19 virus’, ‘the 2019 novel coronavirus’, ‘novel coronavirus’ and ‘COVID‐19’. Studies that evaluated the CT manifestations of common and severe COVID‐19 pneumonia were included. Results Among the 9736 searched results, fifteen articles describing 1453 common patients and 697 severe patients met the inclusion criteria. Based on the CT images, the common patients were less frequent to exhibit consolidation (OR=0.31), pleural effusion (OR=0.19), lymphadenopathy (OR=0.17), crazy‐paving pattern (OR=0.22), interlobular septal thickening (OR=0.27), reticulation (OR=0.20), traction bronchiectasis (OR=0.40) with over 2 lobes involved (OR=0.07) and central distribution (OR=0.18) while more frequent to bear unilateral pneumonia (OR=4.65) involving 1 lobe (OR =13.84) or 2 lobes (OR=6.95) when compared with severe patients. Other CT features including GGOs (P=0.404), air bronchogram (P=0.070), nodule (P=0.093), bronchial wall thickening (P=0.15), subpleural band (P=0.983), vascular enlargement (P=0.207) and peripheral distribution (P=0.668) did not have significant association with the severity of the disease. No publication bias among the selected studies was suggested (Harbord's tests, P>0.05 for all.) Conclusions We obtained reliable estimates of the chest CT manifestations of COVID‐19 pneumonia patients, which might provide an important clue for the diagnosis and classification of COVID‐19 pneumonia.
Authors Elizabeth V. Robilotti, N. Esther Babady, Peter A. Mead, Thierry Rolling, Rocio Perez-Johnston, Marilia Bernardes, Yael Bogler, Mario Caldararo, Cesar J. Figueroa, Michael S. Glickman, Alexa Joanow, Anna Kaltsas, Yeon Joo Lee, Anabella Lucca, Amanda Mariano, Sejal Morjaria, Tamara Nawar, Genovefa A. Papanicolaou, Jacqueline Predmore, Gil Redelman-Sidi, Elizabeth Schmidt, Susan K. Seo, Kent Sepkowitz, Monika K. Shah, Jedd D. Wolchok, Tobias M. Hohl, Ying Taur, Mini Kamboj
ABSTRACT As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.
IJID (INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES)
Authors Pietro De Luca, Claudia Cassandro, Massimo Ralli, Federico Maria Gioacchini, Massimo Re, Ettore Cassandro, Giuseppe Chiarella, Alfonso Scarpa
Authors Dhrubajyoti Bandyopadhyay, Tauseef Akhtar, Adrija Hajra, Manasvi Gupta, Avash Das, Sandipan Chakraborty, Ipsita Pal, Neelkumar Patel, Birendra Amgai, Raktim K. Ghosh, Gregg C. Fonarow, Carl J. Lavie, Srihari S. Naidu
ABSTRACT Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global pandemic with the highest number of affected individuals in the modern era. Not only is the infection inflicting significant morbidity and mortality, but there has also been a significant strain to the health care system and the economy. COVID-19 typically presents as viral pneumonia, occasionally leading to acute respiratory distress syndrome (ARDS) and death. However, emerging evidence suggests that it has a significant impact on the cardiovascular (CV) system by direct myocardial damage, severe systemic inflammatory response, hypoxia, right heart strain secondary to ARDS and lung injury, and plaque rupture secondary to inflammation. Primary cardiac manifestations include acute myocarditis, myocardial infarction, arrhythmia, and abnormal clotting. Several consensus documents have been released to help manage CV disease during this pandemic. In this review, we summarize key cardiac manifestations, their management, and future implications.
Authors Dimitrios Farmakis, Anastasios Giakoumis, Lily Cannon, Michael Angastiniotis, Androulla Eleftheriou
ABSTRACT Objectives Many patients with haemoglobinopathies, including thalassaemia and sickle cell disease, are at increased risk of developing severe complications from the coronavirus disease 2019 (COVID‐19). Although epidemiologic evidence concerning the novel coronavirus (SARS‐CoV‐2) infection in these patients is currently lacking, the COVID‐19 pandemic represents a significant challenge for haemoglobinopathy patients, their families and their attending physicians. Methods The present statement summarizes the key challenges concerning the management of haemoglobinopathies, with particular focus on patients with either transfusion‐dependent or non‐transfusion‐dependent thalassaemia, identifies the gaps in knowledge and suggests measures and strategies to deal with the pandemic, based on available evidence and expert opinions. Key areas covered include patients’ risk level, adaptation of haemoglobinopathy care, safety of blood transfusions, blood supply challenges, and lifestyle and nutritional considerations. Conclusions The proposed measures and strategies may be useful as a blueprint for other disorders which require regular hospital visits, as well as for the timely adaptation of patient care during similar future pandemics.
Authors Hendrik Schulze-Koops, Klaus Krueger, Christof Specker
Authors Xiang Hu, Xiaoqiong Pan, Wei Zhou, Xuejiang Gu, Feixia Shen, Bo Yang, Zhen Hu
ABSTRACT Background/objectives During the 2019 coronavirus disease (COVID-19) outbreak, obesity may contribute to COVID-19 transmission and deterioration. In addition, many patients with COVID-19 infection have suffered liver damage which might contribute to a worse prognosis. We conducted a clinical epidemiological analysis to investigate the association of overweight/obesity and abnormal liver function (ALF) with hospitalized duration in patients infected with COVID-19. Subjects/methods Fifty-eight patients with diagnosed COVID-19 (22 women & 36 men; average age: 49.2 ± 13.1 yr) were included, and their clinical data were collected at The Second Affiliated and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang. Overweight/obesity was determined as body mass index (BMI) ≥24 kg/m2, ALF was determined as alanine aminotransferase >40 U/L, and prolonged hospitalization was lasting more than the median value of the hospitalized days (19 days) in this population. Results The proportions of prolonged hospitalization were elevated in patients with overweight/obesity and ALF compared with those without overweight/obesity (62.1% versus 26.1%, P = 0.010) and those without ALF (70.6% versus 41.5%, P = 0.043). Kaplan–Meier analysis showed that the hospitalized duration was increased from the patients with neither overweight/obesity nor ALF to those with either overweight/obesity or ALF, and to those with both of overweight/obesity and ALF (mean with 95% confidence interval: 16.4 [14.5–18.3] versus 25.3 [21.6–29.1] versus 28.3 [24.6–32.0], P for trend = 0.001). Being discharged from hospital in time was inversely and independently associated with BMI (hazard ratio [HR] = 0.75, 95% CI: 0.63–0.90, P for trend = 0.002) and ALT (HR = 0.95, 95% CI: 0.92–0.99, P for trend = 0.007). Conclusions Present findings suggested that overweight/obesity and/or ALF contributed to predicting a probability of prolonged hospitalization in patients with COVID-19 infection, to whom extra attentions and precautions should be paid during clinical treatments.
Authors Chrysanthi Skevaki, Paraskevi C.Fragkou, Chongsheng Cheng, Min Xie, Harald Renz
Authors Alessandra D’Abramoa, Luciana Leporea, Claudia Palazzoloa, Filippo Barrecab, Giuseppina Liuzzia, Eleonora Lallea , Emanuele Nicastria
ABSTRACT A case of acute respiratory distress syndrome due to SARS-CoV-2 and Influenza A co-infection and a mini-review of the literature is reported. Even in COVID-19 epidemics, the early identification of concurrent respiratory pathogens is important to improve etiological diagnosis, preventive measures and patients’ clinical management and outcome.
Authors Micaela Fredi, Ilaria Cavazzana, Liala Moschetti, Laura Andreoli, Franco Franceschini
EDIZIONE MINERVA MEDICA
Authors Giulia PILLONI, Fabio SPANU, Irene FASCE, Alessandro ALì, Antonio VENTIMIGLIA, Marco MAIELLO, Luca BRUZZONE, Bernarda CAGETTI
CAMBRIDGE UNIVERSITY PRESS
Authors Alessandro Costa, Eric S. Weinstein, D. Ruby Sahoo, Stanley C. Thompson, Roberto Faccincani, Luca Ragazzoni
ABSTRACT v Over the years, the practice of medicine has evolved from authority-based to experience-based to evidence-based with the introduction of the scientific process, clinical trials, and outcomes-based data analysis (Tebala GD. Int J Med Sci. 2018;15(12):1397-1405). The time required to perform the necessary randomized controlled trials, a systematic literature review, and meta-analysis of these trials to then create, accept, promulgate, and educate the practicing clinicians to use the evidence-based clinical guidelines is typically measured in years. When the severe acute respiratory syndrome novel coronavirus-2 (SARS-nCoV-2) pandemic commenced in Wuhan, China at the end of 2019, there were few available clinical guidelines to deploy, let alone adapt and adopt to treat the surge of coronavirus disease 2019 (COVID-19) patients. The aim of this study is to first explain how clinical guidelines, on which bedside clinicians have grown accustomed, can be created in the midst of a pandemic, with an evolving scientific understanding of the pathophysiology of the hypercoagulable state. The second is to adapt and adopt current venous thromboembolism diagnostic and treatment guidelines, while relying on the limited available observational reporting of COVID-19 patients to create a comprehensive clinical guideline to treat COVID-19 patients.
Authors Mattia BELLAN, Francesco GAVELLI, Eyal HAYDEN, Filippo PATRUCCO, Daniele SODDU, Anita Rebecca PEDRINELLI, Micol Giulia CITTONE, Eleonora RIZZI, Giuseppe Francesco CASCIARO, Veronica VASSIA, Raffaella LANDI, Mirta MENEGATTI, Maria Luisa GASTALDELLO, Michela BELTRAME, Emanuela LABELLA, Stelvio TONELLO, Gian Carlo AVANZI, Mario PIRISI, Luigi Mario CASTELLO, Pier Paolo SAINAGHI
ABSTRACT Background The coronavirus disease (COVID-19) outbreak is putting the European National Health Systems under pressure. Interestingly, Emergency Department (ED) referrals for reasons other than Covid-19 seem to have declined steeply. In the present paper, we aimed to verify how the Covid-19 outbreak changed ED referral pattern. Methods We retrospectively reviewed the clinical records of patients referred to the ED of a University Hospital in Northern Italy from 1st March to 13th April 2020. We compared the following data with those belonging to the same period in 2019: number of EDs accesses, rate of hospital admission, frequencies of the most common causes of ED referral, priority codes of access. Results The number of ED referrals during the Covid-19 outbreak was markedly reduced when compared to the same period in 2019 (3059 vs. 5691;-46.3%). Conversely, the rate of hospital admission raised from 16.9% to 35.4% (p<0.0001), with a shift toward higher priority codes of ED admission. In 2020, we observed both a reduction of the number of patients referred for both traumatic (513, 16.8% vs. 1544, 27.1%; χ2=118.7, p<0.0001) and non-traumatic (4147 vs. 2546) conditions. Among the latter, suspected Covid-19 accounted for 1101 (43.2%) accesses. Conclusions The Covid-19 pandemic completely changed the pattern of ED referral in Italy, with a marked reduction of the accesses to the hospitals. This could be related to a limited exposure to traumas and to a common fear of being infected during EDs in-stay. This may limit the misuse of EDs for non- urgent conditions, but may also delay proper referrals for urgent conditions.
Authors Federico Ghidinelli, Anna Bianchi
EUROPEAN HEART JOURNAL
Authors Akshar Jaglan , Sarah Roemer , M. Fuad Jan , Bijoy K. Khandheria
ACCP (AMERICAN COLLEGE OF CLINICAL PHAMARCOLOGY)
Authors Gina Pastino
Authors T. Seitz, W. Hoepler, L. Weseslindtner, J. H. Aberle, S. W. Aberle, E. Puchhammer-Stoeckl, S. Baumgartner, M. Traugott, M. Karolyi, E. Pawelka, I. Niculescu, E. Friese, S. Neuhold, D. Stahl, C. Madl, A. Zoufaly, C. Wenisch, H. Laferl
ABSTRACT We report the successful management of a patient with severe respiratory failure due to COVID-19 admitted to an intensive care unit complicated by secondary catheter-related infection of Candida glabrata. We are discussing some of the clinical challenges and the pitfalls in molecular diagnosis of SARS-CoV-2, including the fact that a positive PCR result may not always reflect infectiousness.
Authors Isaac H. Solomon, Erica Normandin, Shamik Bhattacharyya, Shibani S. Mukerji, Kiana Keller, Ahya S. Ali, Gordon Adams, Jason L. Hornick, Robert F. Padera, Jr., Pardis Sabeti
Authors Aki Sakurai, Toshiharu Sasaki, Shigeo Kato, Masamichi Hayashi, Sei-ichiro Tsuzuki, Takuma Ishihara, Mitsunaga Iwata, Zenichi Morise, Yohei Do
Authors Francesco Doglietto, Marika Vezzoli, Federico Gheza, Gian Luca Lussardi, Marco Domenicucci, Luca Vecchiarelli, Luca Zanin, Giorgio Saraceno, Liana Signorini, Pier Paolo Panciani, Francesco Castelli, Roberto Maroldi, Francesco Antonio Rasulo, Mauro Roberto Benvenuti, Nazario Portolani, Stefano Bonardelli, Giuseppe Milano, Alessandro Casiraghi, Stefano Calza, Marco Maria Fontanella
ABSTRACT Importance There are limited data on mortality and complications rates in patients with coronavirus disease 2019 (COVID-19) who undergo surgery. Objective To evaluate early surgical outcomes of patients with COVID-19 in different subspecialties. Design, Setting, and Participants This matched cohort study conducted in the general, vascular and thoracic surgery, orthopedic, and neurosurgery units of Spedali Civili Hospital (Brescia, Italy) included patients who underwent surgical treatment from February 23 to April 1, 2020, and had positive test results for COVID-19 either before or within 1 week after surgery. Gynecological and minor surgical procedures were excluded. Patients with COVID-19 were matched with patients without COVID-19 with a 1:2 ratio for sex, age group, American Society of Anesthesiologists score, and comorbidities recorded in the surgical risk calculator of the American College of Surgeons National Surgical Quality Improvement Program. Patients older than 65 years were also matched for the Clinical Frailty Scale score. Exposures Patients with positive results for COVID-19 and undergoing surgery vs matched surgical patients without infection. Screening for COVID-19 was performed with reverse transcriptase–polymerase chain reaction assay in nasopharyngeal swabs, chest radiography, and/or computed tomography. Diagnosis of COVID-19 was based on positivity of at least 1 of these investigations. Main Outcomes and Measures The primary end point was early surgical mortality and complications in patients with COVID-19; secondary end points were the modeling of complications to determine the importance of COVID-19 compared with other surgical risk factors. Results Of 41 patients (of 333 who underwent operation during the same period) who underwent mainly urgent surgery, 33 (80.5%) had positive results for COVID-19 preoperatively and 8 (19.5%) had positive results within 5 days from surgery. Of the 123 patients of the combined cohorts (78 women [63.4%]; mean [SD] age, 76.6 [14.4] years), 30-day mortality was significantly higher for those with COVID-19 compared with control patients without COVID-19 (odds ratio [OR], 9.5; 95% CI, 1.77-96.53). Complications were also significantly higher (OR, 4.98; 95% CI, 1.81-16.07); pulmonary complications were the most common (OR, 35.62; 95% CI, 9.34-205.55), but thrombotic complications were also significantly associated with COVID-19 (OR, 13.2; 95% CI, 1.48-∞). Different models (cumulative link model and classification tree) identified COVID-19 as the main variable associated with complications. Conclusions and Relevance In this matched cohort study, surgical mortality and complications were higher in patients with COVID-19 compared with patients without COVID-19. These data suggest that, whenever possible, surgery should be postponed in patients with COVID-19.
AGING
Authors Mikhail V. Blagosklonny
ABSTRACT COVID-19 is not deadly early in life, but mortality increases exponentially with age, which is the strongest predictor of mortality. Mortality is higher in men than in women, because men age faster, and it is especially high in patients with age-related diseases, such as diabetes and hypertension, because these diseases are manifestations of aging and a measure of biological age. At its deepest level, aging (a program-like continuation of developmental growth) is driven by inappropriately high cellular functioning. The hyperfunction theory of quasi-programmed aging explains why COVID-19 vulnerability (lethality) is an age-dependent syndrome, linking it to other age-related diseases. It also explains inflammaging and immunosenescence, hyperinflammation, hyperthrombosis, and cytokine storms, all of which are associated with COVID-19 vulnerability. Anti-aging interventions, such as rapamycin, may slow aging and age-related diseases, potentially decreasing COVID-19 vulnerability.
Authors Gemelli Against COVID-19 Post-Acute Care Study Group
ABSTRACT For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients.
CARDIOLOGY IN THE YOUNG
Authors Paolo Ferrero, Isabelle Piazza, Matteo Ciuffreda
ABSTRACT Little is know about COVID-19 outcome in specific populations such as Adult congenital heart disease (ACHD) patients. We report three cases of adult patients with similar underlying dis- ease with completely different clinical severity at the time of COVID-19 infection. The patient with the most severe clinical course was obese and diabetic, suggesting that COVID-19 mortal- ity and morbidity in Adult congenital heart disease patients might be independent of anatomic complexity.
Authors Marian Knight, Kathryn Bunch, Nicola Vousden, Edward Morris, Nigel Simpson, Chris Gale, Patrick O’Brien, Maria Quigley, Peter Brocklehurst, Jennifer J Kurinczuk
ABSTRACT Objectives To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants. Design Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS). Setting All 194 obstetric units in the UK. Participants 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020. Main outcome measures Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission. Results The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth. Conclusions Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation.
Authors Julie Toubiana, Clément Poirault, Alice Corsia, Fanny Bajolle, Jacques Fourgeaud, François Angoulvant, Agathe Debray, Romain Basmaci, Elodie Salvador, Sandra Biscardi, Pierre Frange, Martin Chalumeau, Jean-Laurent Casanova, Jérémie F Cohen,Slimane Allali
ABSTRACT Objectives To describe the characteristics of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to evaluate a potential temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design Prospective observational study. Setting General paediatric department of a university hospital in Paris, France. Participants 21 children and adolescents (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020. Main outcome measures The primary outcomes were clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus. Results 21 children and adolescents (median age 7.9 (range 3.7-16.6) years) were admitted with features of Kawasaki disease over a 15 day period, with 12 (57%) of African ancestry. 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms during the early stage of illness and high levels of inflammatory markers. 19 (90%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By 15 May 2020, after 8 (5-17) days of hospital stay, all patients were discharged home. Conclusions The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.
Authors José Manuel Abalo-Lojo, Jéssica María Pouso-Diz, Francisco Gonzalez
Authors Maria Luisa Gasparri, Oreste Davide Gentilini, Diana Lueftner, Thorsten Kuehn, Orit Kaidar-Person, Philip Poortmans
Abstract Background Corona Virus Disease 19 (COVID-19) had a worldwide negative impact on healthcare systems, which were not used to coping with such pandemic. Adaptation strategies prioritizing COVID-19 patients included triage of patients and reduction or re-allocation of other services. The aim of our survey was to provide a real time international snapshot of modifications of breast cancer management during the COVID-19 pandemic. Methods A survey was developed by a multidisciplinary group on behalf of European Breast Cancer Research Association of Surgical Trialists and distributed via breast cancer societies. One reply per breast unit was requested. Results In ten days, 377 breast centres from 41 countries completed the questionnaire. RT-PCR testing for SARS-CoV-2 prior to treatment was reported by 44.8% of the institutions. The estimated time interval between diagnosis and treatment initiation increased for about 20% of institutions. Indications for primary systemic therapy were modified in 56% (211/377), with upfront surgery increasing from 39.8% to 50.7% (p < 0.002) and from 33.7% to 42.2% (p < 0.016) in T1cN0 triple-negative and ER-negative/HER2-positive cases, respectively. Sixty-seven percent considered that chemotherapy increases risks for developing COVID-19 complications. Fifty-one percent of the responders reported modifications in chemotherapy protocols. Gene-expression profile used to evaluate the need for adjuvant chemotherapy increased in 18.8%. In luminal-A tumours, a large majority (68%) recommended endocrine treatment to postpone surgery. Postoperative radiation therapy was postponed in 20% of the cases. Conclusions Breast cancer management was considerably modified during the COVID-19 pandemic. Our data provide a base to investigate whether these changes impact oncologic outcomes.
The Lancet
Authors Lennard Y W Lee, Jean Baptiste Cazier, T Starkey, C D Turnbull, UK Coronavirus Cancer Monitoring Project Team, Rachel Kerr, Gary Middleton
Authors Nicole M Kuderer, Toni K Choueiri*, Dimpy P Shah, Yu Shyr, Samuel M Rubinstein, Donna R Rivera, Sanjay Shete, Chih-Yuan Hsu, Aakash Desai, Gilberto de Lima Lopes Jr, Petros Grivas, Corrie A Painter, Solange Peters, Michael A Thompson, Ziad Bakouny, Gerald Batist, Tanios Bekaii-Saab, Mehmet A Bilen, Nathaniel Bouganim, Mateo Bover Larroya, Daniel Castellano, Salvatore A Del Prete, Deborah B Doroshow, Pamela C Egan, Arielle Elkrief, Dimitrios Farmakiotis, Daniel Flora, Matthew D Galsky, Michael J Glover, Elizabeth A Griffiths, Anthony P Gulati, Shilpa Gupta, Navid Hafez, Thorvardur R Halfdanarson, Jessica E Hawley, Emily Hsu, Anup Kasi, Ali R Khaki, Christopher A Lemmon, Colleen Lewis, Barbara Logan, Tyler Masters, Rana R McKay, Ruben A Mesa, Alicia K Morgans, Mary F Mulcahy, Orestis A Panagiotou, Prakash Peddi, Nathan A Pennell, Kerry Reynolds, Lane R Rosen, Rachel Rosovsky, Mary Salazar, Andrew Schmidt, Sumit A Shah, Justin A Shaya, John Steinharter, Keith E Stockerl-Goldstein, Suki Subbiah, Donald C Vinh, Firas H Wehbe, Lisa B Weissmann, Julie Tsu-Yu Wu, Elizabeth Wulff-Burchfield, Zhuoer Xie, Albert Yeh, Peter P Yu, Alice Y Zhou, Leyre Zubiri, Sanjay Mishra, Gary H Lyman*, Brian I Rini, Jeremy L Warner
Authors Hani M. Mahmoud-Elsayed, William E. Moody, William M. Bradlow, Ayisha M. Khan-Kheil, Jonathan Senior, Lucy E. Hudsmith, Richard P. Steeds
ABSTRACT The aim of this study was to characterize the echocardiographic phenotype of patients with COVID-19 pneumonia and its relation to biomarkers. Seventy-four patients (59 ± 13 years old, 78% male) admitted with COVID-19 were included after referral for transthoracic echocardiography as part of routine care. A level 1 British Society of Echocardiography transthoracic echocardiography was used to assess chamber size and function, valvular disease, and likelihood of pulmonary hypertension. The chief abnormalities were right ventricle (RV) dilatation (41%) and RV dysfunction (27%). RV impairment was associated with increased D-dimer and C-reactive protein levels. In contrast, left ventricular function was hyperdynamic or normal in most (89%) patients.
Authors Eloi Marijon, Nicole Karam, Daniel Jost, David Perrot, Benoit Frattini, Clément Derkenne, Ardalan Sharifzadehgan, Victor Waldmann, Frankie Beganton,Kumar Narayanan, Antoine Lafont, Wulfran Bougouin, Xavier Jouven
UNIVERSITEIT GENT
Authors Kristl Vonck, Ieme Garrez, Veerle De Herdt, Dimitri Hemelsoet, Guy Laureys, Robrecht Raedt, Paul Boon
ABSTRACT Introduction: Infections with coronaviruses are not always confined to the respiratory tract and various neurological manifestations have been reported. The aim of this study was to perform a review to describe neurological manifestations in patients with COVID -19 and possible neuro -invasive mechanisms of Sars -CoV -2. Methods: Pubmed, Web O fScience and Covid -dedicated databases were searched for the combination of COVID -19 terminology and neurology terminology up to May 10th 2020 . Social media channels were followed -up between March 15th and May 10th 2020 for postings with the same scope. Neurological manifestations were extracted from the identified manuscripts and combined to provide a useful summary for the neurologist in clinical practice. Results: Neurological manifestations potentially related to COVID -19 have been reported in large studies, case series and case reports and include acute cerebrovascular diseases, impaired consciousness, cranial nerve manifestations and auto -immune disorders such as Guillain -Barré Syndrome often present in patients with more severe COVID -19 . Cranial nerve symptoms such as olfactory and gustatory dysfunctions are hig hly prevalent in patients with mild -to -moderate COVID -19 even without associated nasal symptoms and often present in an early stage of the disease Conclusion: Physicians should be aware of the neurological manifestations in patients with COVID -19, especially when rapid clinical deterioration occurs. The neurological symptoms in COVID -19 patients may be due to direct viral neurological injury or indirect neuroinflammatory and autoimmune mechanisms. No antiviral treatments against the virus or vaccines for its prevention are available and the long -term consequences of the infection on human health remain uncertain especially with regards to the neurological system.
Authors A. Berni, D. Malandrino, G. Parenti, M. Maggi, L. Poggesi, A. Peri
Authors Cheryl L Maier, Alexander D Truong, Sara C Auld, Derek M Polly, Christin-Lauren Tanksley, Alexander Duncan
Authors Paul Baracha, and Steven E. Lipshultzc
The BMJ
Authors Christopher M Petrilli, Simon A Jones, Jie Yang, Harish Rajagopalan, Luke O’Donnell, Yelena Chernyak, Katie A Tobin, Robert J Cerfolio, Fritz Francois, Leora I Horwitz
ABSTRACT Objective To describe outcomes of people admitted to hospital with coronavirus disease 2019 (covid-19) in the United States, and the clinical and laboratory characteristics associated with severity of illness. Design Prospective cohort study. Setting Single academic medical center in New York City and Long Island. Participants 5279 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between 1 March 2020 and 8 April 2020. The final date of follow up was 5 May 2020. Main outcome measures Outcomes were admission to hospital, critical illness (intensive care, mechanical ventilation, discharge to hospice care, or death), and discharge to hospice care or death. Predictors included patient characteristics, medical history, vital signs, and laboratory results. Multivariable logistic regression was conducted to identify risk factors for adverse outcomes, and competing risk survival analysis for mortality. Results Of 11 544 people tested for SARS-Cov-2, 5566 (48.2%) were positive. After exclusions, 5279 were included. 2741 of these 5279 (51.9%) were admitted to hospital, of whom 1904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age, with an odds ratio of >2 for all age groups older than 44 years and 37.9 (95% confidence interval 26.1 to 56.0) for ages 75 years and older. Other risks were heart failure (4.4, 2.6 to 8.0), male sex (2.8, 2.4 to 3.2), chronic kidney disease (2.6, 1.9 to 3.6), and any increase in body mass index (BMI) (eg, for BMI >40: 2.5, 1.8 to 3.4). The strongest risks for critical illness besides age were associated with heart failure (1.9, 1.4 to 2.5), BMI >40 (1.5, 1.0 to 2.2), and male sex (1.5, 1.3 to 1.8). Admission oxygen saturation of <88% (3.7, 2.8 to 4.8), troponin level >1 (4.8, 2.1 to 10.9), C reactive protein level >200 (5.1, 2.8 to 9.2), and D-dimer level >2500 (3.9, 2.6 to 6.0) were, however, more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone. Conclusions Age and comorbidities were found to be strong predictors of hospital admission and to a lesser extent of critical illness and mortality in people with covid-19; however, impairment of oxygen on admission and markers of inflammation were most strongly associated with critical illness and mortality. Outcomes seem to be improving over time, potentially suggesting improvements in care.
Authors Annemarie B Docherty, Ewen M Harrison, Christopher A Green, Hayley E Hardwick, Riinu Pius, Lisa Norman, Karl A Holden, Jonathan M Read, Frank Dondelinger, Gail Carson, Laura Merson, James Lee, Daniel Plotkin, Louise Sigfrid, Sophie Halpin, Clare Jackson, Carrol Gamble, Peter W Horby, Jonathan S Nguyen-Van-Tam, Antonia Ho, Clark D Russell, Jake Dunning, Peter JM Openshaw, J Kenneth Baillie, Malcolm G Semple
ABSTRACT Objective To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital. Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission. Participants 20 133 hospital inpatients with covid-19. Main outcome measures Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital. Results The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest comorbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital. Conclusions ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks.
Authors Joseph A Lewnard, Vincent X Liu, Michael L Jackson, Mark A Schmidt, Britta L Jewell, Jean P Flores, Chris Jentz, Graham R Northrup, Ayesha Mahmud, Arthur L Reingold, Maya Petersen, Nicholas P Jewell, Scott Young, Jim Bellows
ABSTRACT Objective To understand the epidemiology and burden of severe coronavirus disease 2019 (covid-19) during the first epidemic wave on the west coast of the United States. Design Prospective cohort study. Setting Kaiser Permanente integrated healthcare delivery systems serving populations in northern California, southern California, and Washington state. Participants 1840 people with a first acute hospital admission for confirmed covid-19 by 22 April 2020, among 9 596 321 healthcare plan enrollees. Analyses of hospital length of stay and clinical outcomes included 1328 people admitted by 9 April 2020 (534 in northern California, 711 in southern California, and 83 in Washington). Main outcome measures Cumulative incidence of first acute hospital admission for confirmed covid-19, and subsequent probabilities of admission to an intensive care unit (ICU) and mortality, as well as duration of hospital stay and ICU stay. The effective reproduction number (RE) describing transmission dynamics was estimated for each region. Results As of 22 April 2020, cumulative incidences of a first acute hospital admission for covid-19 were 15.6 per 100 000 cohort members in northern California, 23.3 per 100 000 in southern California, and 14.7 per 100 000 in Washington. Accounting for censoring of incomplete hospital stays among those admitted by 9 April 2020, the estimated median duration of stay among survivors was 9.3 days (with 95% staying 0.8 to 32.9 days) and among non-survivors was 12.7 days (1.6 to 37.7 days). The censoring adjusted probability of ICU admission for male patients was 48.5% (95% confidence interval 41.8% to 56.3%) and for female patients was 32.0% (26.6% to 38.4%). For patients requiring critical care, the median duration of ICU stay was 10.6 days (with 95% staying 1.3 to 30.8 days). The censoring adjusted case fatality ratio was 23.5% (95% confidence interval 19.6% to 28.2%) among male inpatients and 14.9% (11.8% to 18.6%) among female inpatients; mortality risk increased with age for both male and female patients. Reductions in RE were identified over the study period within each region. Conclusions Among residents of California and Washington state enrolled in Kaiser Permanente healthcare plans who were admitted to hospital with covid-19, the probabilities of ICU admission, of long hospital stay, and of mortality were identified to be high. Incidence rates of new hospital admissions have stabilized or declined in conjunction with implementation of social distancing interventions.
Authors Maximilian Ackermann, Stijn E. Verleden, Mark Kuehnel, Axel Haverich, Tobias Welte, Florian Laenger, Arno Vanstapel, Christopher Werlein, Helge Stark, Alexandar Tzankov, William W. Li, Vincent W. Li, Steven J. Mentzer, Danny Jonigk
ABSTRACT BACKGROUND Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. METHODS We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro–computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression. RESULTS In patients who died from Covid-19–associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth — predominantly through a mechanism of intussusceptive angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001). CONCLUSIONS In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.)
AUSTRALIAN JOURNAL OF GENERAL PRACTICE
Authors Atifur Rahman
Authors Katherine Lisa Whitcroft, Thomas Hummel
Authors Liguori, C., Pierantozzi, M., Spanetta, M., Sarmati, L., Cesta, N., Iannetta, M., Ora, J., Genga Mina, G., Puxeddu, E., Balbi, O., Pezzuto, G., Magrini, A., Rogliani, P., Andreoni, M., Biagio Mercuri
ABSTRACT Objective Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. Methods We included patients hospitalized at the University Hospital of Rome Tor Vergata, medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. Results We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. Conclusions Patients with SARS-CoV2 infection frequently present with sNS. These symptoms were present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.
LEUKEMIA
Authors Weiming Li, Danyu Wang, Jingming Guo, Guolin Yuan, Zhuangzhi Yang, Robert Peter Gale, Yong You, Zhichao Chen, Shiming Chen, Chucheng Wan, Xiaojian Zhu, Wei Chang, Lingshuang Sheng, Hui Cheng, Youshan Zhang, Qing Li, Jun Qin, Hubei Anti-Cancer Association, Li Meng, Qian Jiang
ABSTRACT We studied by questionnaire 530 subjects with chronic myeloid leukaemia (CML) in Hubei Province during the recent SARS-CoV-2 epidemic. Five developed confirmed (N = 4) or probable COVID-19 (N = 1). Prevalence of COVID-19 in our subjects, 0.9% (95% Confidence Interval, 0.1, 1.8%) was ninefold higher than 0.1% (0, 0.12%) reported in normals but lower than 10% (6, 17%) reported in hospitalised persons with other haematological cancers or normal health-care providers, 7% (4, 12%). Co-variates associated with an increased risk of developing COVID-19 amongst persons with CML were exposure to someone infected with SARS-CoV-2 (P = 0.037), no complete haematologic response (P = 0.003) and co-morbidity(ies) (P = 0.024). There was also an increased risk of developing COVID-19 in subjects in advanced phase CML (P = 0.004) even when they achieved a complete cytogenetic response or major molecular response at the time of exposure to SARS-CoV-2. 1 of 21 subjects receiving 3rd generation tyrosine kinase-inhibitor (TKI) developed COVID-19 versus 3 of 346 subjects receiving imatinib versus 0 of 162 subjects receiving 2nd generation TKIs (P = 0.096). Other co-variates such as age and TKI-therapy duration were not significantly associated with an increased risk of developing COVID-19. Persons with these risk factors may benefit from increased surveillance of SARS-CoV-2 infection and possible protective isolation.
NCBI
Authors Saeed Karimi, Amir Arabi,Toktam Shahraki, Sare Safi
ABSTRACT Since there are few reports on the ocular involvement of coronavirus disease 2019 (COVID-19) patients, this study aimed to assess the presence of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in the tears of patients with COVID-19. Methods In this prospective case series, nasopharyngeal and tear sampling of 43 patients with severe COVID-19 were performed. The quantitative reverse transcription polymerase chain reaction (RT-PCR) was conducted to detect SARS-CoV-2. Ocular and systemic signs and symptoms were recorded from their medical history. Results The mean age of patients was 56 ± 13 years. The average disease time from initiation of symptoms was 3.27 days, range: 1–7 days. Forty-one patients (95.3%) had fever at the time of sampling. Only one patient had conjunctivitis. Thirty (69.8%) nasopharyngeal and three (7%) tear samples were positive for SARS-CoV-2. The result of tear sample was positive in the patient with conjunctivitis. All patients with positive tear RT-PCR results had positive nasopharyngeal RT-PCR results. Conclusions Ocular manifestation was rare in this series of severe COVID-19 patients, however, 7% of the patients had viral RNA in their conjunctival secretions. Therefore, possibility of ocular transmission should be considered even in the absence of ocular manifestations.
Authors Jeremy Hsu
EYE
Authors Francesco Aiello, Gabriele Gallo Afflitto, Raffaele Mancino, Ji-Peng Olivia Li, Massimo Cesareo, Clarissa Giannini, Carlo Nucci
ABSTRACT Coronavirus disease 19 (COVID-19) has been described to potentially be complicated by ocular involvement. However, scant information is available regarding severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and ocular structures tropism. We conducted a systematic review of articles referenced in PubMed, Cochrane Library, Web of Science and Chinese Clinical Trial Register (ChiCTR) from December 20, 2019 to April 6, 2020, providing information on the presence of SARS-CoV-2 in cornea, conjunctiva, lacrimal sac, and tears. We excluded ongoing clinical studies as for unobtainable conclusive results. Of 2422 articles, 11 met the inclusion criteria for analysis and were included in the study. None of the studies were multinational. Among the 11 selected papers there were three original articles, one review, four letters, two editorials, and one correspondence letter. Globally, 252 SARS-CoV-2 infected patients were included in our review. The prevalence of ocular conjunctivitis complicating the course of COVID-19 was demonstrated to be as high as 32% in one study only. Globally, three patients had conjunctivitis with a positive tear-PCR, 8 patients had positive tear-PCR in the absence of conjunctivitis, and 14 had conjunctivitis with negative tear-PCR. The majority of the available data regarding SARS-CoV-2 colonization of ocular and periocular tissues and secretions have to be considered controversial. However, it cannot be excluded that SARS-CoV-2 could both infect the eye and the surrounding structures. SARS-CoV-2 may use ocular structure as an additional transmission route, as demonstrated by the COVID-19 patients’ conjunctival secretion and tears positivity to reverse transcriptase-PCR SARS-CoV-2-RNA assay.
Authors Weiming Li, Danyu Wang, Jingming Guo, Guolin Yuan, Zhuangzhi Yang, Robert Peter Gale, Yong You, Zhichao Chen, Shiming Chen, Chucheng Wan, Xiaojian Zhu, Wei Chang, Lingshuang Sheng, Hui Cheng, Youshan Zhang, Qing Li, Jun Qin
ABSTRACT Objectives Since there are few reports on the ocular involvement of coronavirus disease 2019 (COVID-19) patients, this study aimed to assess the presence of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in the tears of patients with COVID-19. Methods In this prospective case series, nasopharyngeal and tear sampling of 43 patients with severe COVID-19 were performed. The quantitative reverse transcription polymerase chain reaction (RT-PCR) was conducted to detect SARS-CoV-2. Ocular and systemic signs and symptoms were recorded from their medical history. Results The mean age of patients was 56 ± 13 years. The average disease time from initiation of symptoms was 3.27 days, range: 1–7 days. Forty-one patients (95.3%) had fever at the time of sampling. Only one patient had conjunctivitis. Thirty (69.8%) nasopharyngeal and three (7%) tear samples were positive for SARS-CoV-2. The result of tear sample was positive in the patient with conjunctivitis. All patients with positive tear RT-PCR results had positive nasopharyngeal RT-PCR results. Conclusions Ocular manifestation was rare in this series of severe COVID-19 patients, however, 7% of the patients had viral RNA in their conjunctival secretions. Therefore, possibility of ocular transmission should be considered even in the absence of ocular manifestations.
Authors Francesco Aiello, Gabriele Gallo Afflitto, Raffaele Mancino, Ji-Peng Olivia Li, Massimo Cesareo, Clarissa Giannini & Carlo Nucci
Wiley Online Library
ABSTRACT Introduction Infections with coronaviruses are not always confined to the respiratory tract and various neurological manifestations have been reported. The aim of this study was to perform a review to describe neurological manifestations in patients with COVID‐19 and possible neuro‐invasive mechanisms of Sars‐CoV‐2. Methods Pubmed, WebOfScience and Covid‐dedicated databases were searched for the combination of COVID‐19 terminology and neurology terminology up to May 10th 2020. Social media channels were followed‐up between March 15th and May 10th 2020 for postings with the same scope. Neurological manifestations were extracted from the identified manuscripts and combined to provide a useful summary for the neurologist in clinical practice. Results Neurological manifestations potentially related to COVID‐19 have been reported in large studies, case series and case reports and include acute cerebrovascular diseases, impaired consciousness, cranial nerve manifestations and auto‐immune disorders such as Guillain‐Barré Syndrome often present in patients with more severe COVID‐19. Cranial nerve symptoms such as olfactory and gustatory dysfunctions are highly prevalent in patients with mild‐to‐moderate COVID‐19 even without associated nasal symptoms and often present in an early stage of the disease. Conclusion Physicians should be aware of the neurological manifestations in patients with COVID‐19, especially when rapid clinical deterioration occurs. The neurological symptoms in COVID‐19 patients may be due to direct viral neurological injury or indirect neuroinflammatory and autoimmune mechanisms. No antiviral treatments against the virus or vaccines for its prevention are available and the long‐term consequences of the infection on human health remain uncertain especially with regards to the neurological system.
Authors Chiara Sartini, Moreno Tresoldi, Paolo Scarpellini, Andrea Tettamanti, Francesco Carcò, Giovanni Landoni, Alberto Zangrillo
JVS
Authors Inayat Hussain Khan, Sugeevan Savarimuthu, Marco Shiu Tsun, Leung, Amer Harky
ABSTRACT COVID-19 first presented in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20th, 2020, there have been more than 2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. It is uncertain what the total incidences of thrombotic events in COVID-19 patients is currently at. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.
Authors Rachael Jones, Mark Nelson,Margherita Bracchi,David Asboe,Marta Boffito
Authors: Rachael Jones, Mark Nelson,Margherita Bracchi,David Asboe,Marta Boffito
ASTMH (THE AMERICAN SOCIETY OF TROPICAL MEDICINE AND HYGIENE)
Authors Marcello A. Orsi, Giancarlo Oliva, Michaela Cellina
Authors Jenny Lumley Holmes, Simon Brake, Mark Docherty, Richard Lilford, Sam Watson
Authors Inayat Hussain Khan, Sugeevan Savarimuthu, Marco Shiu Tsun Leung, Amer Harky
ABSTRACT COVID-19 first appeared in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20, 2020, there have been >2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. The total incidence of thrombotic events in COVID-19 patients is currently uncertain. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.
Authors Lorenzo Piemonti, Giovanni Landoni
ABSTRACT For those who work in the field of islet transplantation, the microvascular coronavirus disease 2019 (COVID‐19) lung vessels obstructive thrombo‐inflammatory syndrome (recently referred to as MicroCLOTS) is familiar, as one cannot fail to recognize the presence of similarities with the instant blood mediated inflammatory reaction (IBMIR) occurring in the liver hours and days after islet infusion. Evidence in both MicroCLOTS and IBMIR suggests the involvement of the coagulation cascade and complement system activation and proinflammatory chemokines/cytokines release. Identification and targeting of pathway(s) playing a role as “master regulator(s)” in the post‐islet transplant detrimental inflammatory events could be potentially useful to suggest innovative COVID‐19 treatments and vice versa. Scientific organizations across the world are fighting the COVID‐19 pandemic. Islet transplantation, and more generally the transplantation scientific community, could contribute by suggesting strategies for innovative approaches. At the same time, in the near future, clinical trials in COVID‐19 patients will produce an enormous quantity of clinical and translational data on the control of inflammation and complement/microthrombosis activation. These data will represent a legacy to be transformed into innovation in the transplant field. It will be our contribution to change a dramatic event into advancement for the transplant field and ultimately for our patients.
FRONTIERS IN MICROBIOLOGY
Authors Aimee K. Murray
Authors Russell M Viner, Elizabeth Whittaker
Authors Lucio Verdoni, Angelo Mazza, Annalisa Gervasoni, Laura Martelli, Maurizio Ruggeri, Matteo Ciuffreda, Ezio Bonanomi, Lorenzo D'Antiga
Authors Liping Sun, Gang Liu, Fengxiang Song, Nannan Shi, Fengjun Liu, Shenyang Li, Ping Li, Weihan Zhang, Xiao Jiang, Yongbin Zhang, Lining Sun, Xiong Chen, Yuxin Shi
Background Despite the death rate of COVID-19 is less than 3%, the fatality rate of severe/critical cases is high, according to World Health Organization (WHO). Thus, screening the severe/critical cases before symptom occurs effectively saves medical resources. Methods and materials In this study, all 336 cases of patients infected COVID-19 in Shanghai to March 12th, were retrospectively enrolled, and divided in to training and test datasets. In addition, 220 clinical and laboratory observations/records were also collected. Clinical indicators were associated with severe/critical symptoms were identified and a model for severe/critical symptom prediction was developed. Results Totally, 36 clinical indicators significantly associated with severe/critical symptom were identified. The clinical indicators are mainly thyroxine, immune related cells and products. Support Vector Machine (SVM) and optimized combination of age, GSH, CD3 ratio and total protein has a good performance in discriminating the mild and severe/critical cases. The area under receiving operating curve (AUROC) reached 0.9996 and 0.9757 in the training and testing dataset, respectively. When the using cut-off value as 0.0667, the recall rate was 93.33% and 100% in the training and testing datasets, separately. Cox multivariate regression and survival analyses revealed that the model significantly discriminated the severe/critical cases and used the information of the selected clinical indicators. Conclusion The model was robust and effective in predicting the severe/critical COVID cases.
Authors Sabel Garrido, Rodrigo Liberal, Guilherme Macedo
ABSTRACT Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative pathogen of coronavirus disease 2019 (COVID‐19), became a global threat to human health. Liver impairment has been frequently reported as a common manifestation, although its clinical significance is still unclear, particularly in patients with underlying chronic liver disease (CLD). Aims To summarize the changes in liver function tests during SARS‐CoV‐2 infection and the impact of COVID‐19 in patients with underlying CLD. Methods A literature review using online database Pubmed was done using the search terms “SARS‐CoV‐2”, “COVID‐19”, “liver”, “cirrhosis” and “liver transplantation”. Results COVID‐19 is frequently associated with different degrees of abnormal liver function tests, most notably transaminases, which are usually transitory and of mild degree. Available evidence suggests that liver injury may result from direct pathogenic effect by the virus, systemic inflammation or toxicity from commonly used drugs in this subset of patients. SARS‐CoV‐2 infection in children is associated with minimal or no increase in liver enzymes, thus the presence of abnormal liver function tests should trigger evaluation for underlying liver diseases. Although it seems that patients with CLD are not at greater risk for acquiring the infection, those with cirrhosis, hepatocellular carcinoma, non‐alcoholic fatty liver disease, autoimmune liver diseases or liver transplant may have a greater risk for severe COVID‐19. Conclusions Abnormal liver function tests during the course of COVID‐19 are common, though clinically significant liver injury is rare. Further research is needed focusing on the effect of existing liver‐related comorbidities on treatment and outcome of COVID‐19.
Authors Ren Mao, Yun Qiu, Jin-Shen He, Jin-Yu Tan, Xue-Hua Li, Jie Liang, Jun Shen, Liang-Ru Zhu, Yan Chen, Marietta Iacucci, Siew C Ng, Subrata Ghosh, Min-Hu Chen
Authors Marcel Levi, Jecko Thachil, Toshiaki Iba, Jerrold H Levy
OURNAL OF CLINICAL MEDICINE
Authors Kensuke Matsushita, Benjamin Marchandot, Laurence Jesel, Patrick Ohlmann, Olivier Morel
ABSTRACT The recent outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has been declared a public health emergency of international concern. COVID-19 may present as acute respiratory distress syndrome in severe cases, and patients with pre-existing cardiovascular comorbidities are reported to be the most vulnerable. Notably, acute myocardial injury, determined by elevated high-sensitivity troponin levels, is commonly observed in severe cases, and is strongly associated with mortality. Therefore, understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for critically ill patients. In this review, we summarize the rapidly evolving data and highlight the cardiovascular considerations related to COVID-19.
Authors Paul E Verweij, Jean-Pierre Gangneux, Matteo Bassetti, Roger J M Brüggemann, Oliver A Cornely, Philipp Koehler, Cornelia Lass-Flörl, Frank L van de Veerdonk, Arunaloke Chakrabarti, Martin Hoenigl, on behalf of the European Confederation of Medical Mycology, the International Society for Human and Animal Mycology, the European Society for Clinical Microbiology and Infectious Diseases Fungal Infection Study Group, and the ESCMID Study Group for Infections in Critically Ill Patients
Authors Andrea De Maria, Paola Varese, Chiara Dentone, Emanuela Barisione, Matteo Bassetti
Authors A. M. Isidori, E. A. Jannini, A. Lenzi, E. Ghigo & the Board of Full Professors in Endocrinology, Directors of the Endocrinology, Metabolic Disorders Residency Program
Authors Shelley Riphagen, Xabier Gomez,Carmen Gonzalez-Martinez, Nick Wilkinson, Paraskevi Theocharis
Authors Kenrie P Y Hui, Man-Chun Cheung, Ranawaka A P M Perera, Ka-Chun Ng, Christine H T Bui, John C W Ho, Mandy M T Ng, Denise I T Kuok, Kendrick C Shih, Sai-Wah Tsao, Leo L M Poon, Malik Peiris, John M Nicholls, Michael C W Chan
SUMMARY Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. Methods We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. Findings SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. Interpretation The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. Funding US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.
Authors Ottavio Piccin, Riccardo Albertini, Umberto Caliceti, Ottavio Cavicchi, Eleonora Cioccoloni, MarcoDemattè, Gian GaetanoFerri, Giovanni Macrì, Pietro Marrè, Irene Pelligra, Domenico Saggese, Patrizia Schiavon, Vittorio Sciarretta, Giovanni Sorrenti
ABSTRACT In Italy, we have experienced Europe's first and largest coronavirus outbreak. Based on our preliminary experience, we discuss the challenges in performing tracheotomy and tracheostoma care in the setting of a new pathogen.
Authors Antonio Pisano, Giovanni Landoni, Luigi Verniero, Alberto Zangrillo
Authors Laine E. Thomas, Robert O. Bonow, Michael J. Pencina
Authors Paolo Perini, Bilal Nabulsi, Claudio Bianchini Massoni, Matteo Azzarone, Antonio Freyrie
WINLEY ONLINE LIBRARY
Authors Yuqing Li, Biao Ren, Xian Peng, Tao Hu, Jiyao Li, Tao Gong, Boyu Tang, Xin Xu, Xuedong Zhou
SUMMARY SARS-CoV-2, a novel emerging coronavirus, has caused severe disease (COVID-19), and rapidly spread worldwide since the beginning of 2020. SARS-CoV-2 mainly spreads by coughing, sneezing, droplet inhalation, and contact. SARS-CoV-2 has been detected in saliva samples, making saliva a potential transmission route for COVID-19. The participants in dental practice confront a particular risk of SARS-CoV-2 infection due to close contact with the patients and potential exposure to saliva-contaminated droplets and aerosols generated during dental procedures. In addition, saliva-contaminated surfaces could lead to potential cross-infection. Hence, the control of saliva-related transmission in the dental clinic is critical, particularly in the epidemic period of COVID-19. Based on our experience of the COVID-19 epidemic, some protective measures that can help reduce the risk of saliva-related transmission are suggested, in order to avoid the potential spread of SARS-CoV-2 among patients, visitors, and dental practitioners.Accepted Article
Authors SEBASTIAN L. JOHNSON
ABSTRACT When I first read the manuscript that accompanies this editorial, upon its online publication on February 19th 2020(1), COVID‐19 had already killed 2118 people in China, but only one person in Europe – an 80‐year‐old tourist from China, who died in France on the 15th February. I read the manuscript with grim fascination, as it was clear that SARS‐CoV‐2 had spread very rapidly in China which already had 74,576 cases and in South Korea which already had 58 cases, and that it was then invading Europe also, as France already had 12 cases, Germany 16, the UK 9, Italy 3, Spain 2 and other countries too.
THIEME
Authors Danilo Buonsenso , Simonetta Costa, Maurizio Sanguinetti, Paola Cattani, Brunella Posteraro, Simona Marchetti, Brigida Carducci, Antonio Lanzone, Enrica Tamburrini, Giovanni Vento, Piero Valentini
ABSTRACT Objective To date, no information on late-onset infection in newborns to mother with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contracted in pregnancy are available. This study aimed to evaluate postdischarge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2. Study Design This is an observational study of neonates born to mothers with coronavirus disease 2019 (COVID-19). Results Seven pregnant women with documented SARS-CoV-2 infection have been evaluated in our institution. One woman had a spontaneous abortion at 8 weeks of gestational age, four women recovered and are still in follow-up, and two women delivered. Two newborns were enrolled in the study. At birth and 3 days of life, newborns were negative to SARS-CoV-2. At 2-week follow-up, one newborn tested positive although asymptomatic. Conclusion Our findings highlight the importance of follow-up of newborns to mothers with COVID-19 in pregnancy, since they remain at risk of contracting the infection in the early period of life and long-term consequences are still unknown.
Authors Niccolò Parri, Matteo Lenge, Danilo Buonsenso
CMAJ
Authors Stephanie G. Lee, Michael Fralick, Michelle Sholzberg
Authors Mariapia Sormani
Authors W. Guan, Z. Ni, Yu Hu, W. Liang, C. Ou, J. He, L. Liu, H. Shan, C. Lei, D.S.C. Hui, B. Du, L. Li, G. Zeng, K.-Y. Yuen, R. Chen, C. Tang, T. Wang, P. Chen, J. Xiang, S. Li, Jin-lin Wang, Z. Liang, Y. Peng, L. Wei, Y. Liu, Ya-hua Hu, P. Peng, Jian-ming Wang, J. Liu, Z. Chen, G. Li, Z. Zheng, S. Qiu, J. Luo, C. Ye, S. Zhu, N. Zhong
ABSTRACT BACKGROUND Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
ELSIEVER
Authors F.A.Klok, M.J.H.A.Kruip, N.J.M.van der Meer, M.S.Arbous, D.Gommers, K.M.Kant, F.H.J.Kaptein, J.van Paassen, M.A.M.Stals, M.V.Huisman, H.Endeman
ABSTRACT Introduction We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses. Methods We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first. Results We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41–57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091–0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4–12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35–1.8). Conclusion In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.
Authors C. Galván Casas A. Català G. Carretero Hernández P. Rodríguez‐Jiménez D. Fernández Nieto A. Rodríguez‐Villa Lario I. Navarro Fernández R. Ruiz‐Villaverde D. Falkenhain M. Llamas Velasco J. García‐Gavín O. Baniandrés C. González‐Cruz V. Morillas‐Lahuerta X. Cubiró I. Figueras Nart G. Selda‐Enriquez J. Romaní X. Fustà‐Novell A. Melian‐Olivera M. Roncero Riesco P. Burgos‐Blasco J. Sola Ortigosa M. Feito Rodriguez I. García‐Doval
ABSTRACTBackground Cutaneous manifestations of COVID‐19 disease are poorly characterized.Objectives To describe the cutaneous manifestations of COVID‐19 disease and to relate them to other clinical findingsMethods Nationwide case collection survey of images and clinical data. Using a consensus, we described 5 clinical patterns. We later described the association of these patterns with patient demographics, timing in relation to symptoms of the disease, severity, and prognosis.Results Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular).Conclusions We provide a description of the cutaneous manifestations associated with COVID‐19 infection. These may help clinicians approach patients with the disease and recognize paucisymptomatic cases.
Authors Guangtong Deng, Mingzhu Yin, Xiang Chen and Furong Zeng
Authors Elisabeth Mahase
Authors Daniel E. Leisman, Clifford S. Deutschman & Matthieu Legrand
Authors Ovidio De Filippo, Fabrizio D’Ascenzo, Filippo Angelini, Pier Paolo Bocchino, Federico Conrotto, Andrea Saglietto, Gioel Gabrio Secco, Gianluca Campo, Guglielmo Gallone, Roberto Verardi, et all
NATURE REVIEWS
Authors Matthew Zirui Tay, Chek Meng Poh, Laurent Rénia, Paul A. MacAry & Lisa F. P. Ng
ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.
Authors Rajesh T. Gandhi, John B. Lynch, M.P.H, Carlos del Rio
Authors Michael J Cox, Nicholas Loman, Debby Bogaert, Justin O’Grady
Authors M.M. Arons, K.M. Hatfield, S.C. Reddy, A. Kimball, A. James, J.R. Jacobs, J. Taylor, K. Spicer, A.C. Bardossy, L.P. Oakley, S. Tanwar, J.W. Dyal, J. Harney, Z. Chisty, J.M. Bell, M. Methner, P. Paul, C.M. Carlson, H.P. McLaughlin, N. Thornburg, S. Tong, A. Tamin, Y. Tao, A. Uehara, J. Harcourt, S. Clark, C. Brostrom-Smith, L.C. Page, M. Kay, J. Lewis, P. Montgomery, N.D. Stone, T.A. Clark, M.A. Honein, J.S. Duchin, and J.A. Jernigan
ABSTRACT BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. METHODS We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were catego- rized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. RESULTS Twenty-three days after the first positive test result in a resident at this skilled nurs- ing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 resi- dents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 pre- symptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. CONCLUSIONS Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymp- tomatic at the time of testing and most likely contributed to transmission. Infec- tion-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.
Authors Denis Doyen, Pamela Moceri, Dorothée Ducreux, Jean Dellamonica
Eurosurveillance
Authors Marta Colaneri, Paolo Sacchi, Valentina Zuccaro, Simona Biscarini, Michele Sachs, Silvia Roda, Teresa Chiara Pieri, Pietro Valsecchi, Antonio Piralla, Elena Seminari, Angela Di Matteo, Stefano Novati, Laura Maiocchi, Layla Pagnucco, Marcello Tirani, Fausto Baldanti, Francesco Mojoli , Stefano Perlini, Raffaele Bruno
ABSTRACTWe describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21–28 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age > 65 years, antiviral treatment and for severe disease, lactate dehydrogenase > 300 mg/dL.
Authors Yuhao Zhanga,, Xiuchao Gengb,, Yanli Tana, Qiang Lic, Can Xua, Jianglong Xua, Liangchao Haoa, Zhaomu Zenga, Xianpu Luod, Fulin Liue, Hong Wanga
Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.
Authors Muthiah Vaduganathan, Orly Vardeny, Pharm, Thomas Michel, John J.V. McMurray, Marc A. Pfeffer, and Scott D. Solomon
WILEY
Authors Gisondi P, Piaserico S, Conti A, Naldi L
ABSTRACT Since the first case of “pneumonia of unknown aetiology” was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognised thereafter as “severe acute respiratory syndrome coronavirus 2” (SARS‐CoV‐2) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease‐19 (COVID‐ 19) and satisfying the epidemiological criteria for a label of “pandemic.” The ongoing SARS‐CoV‐2 pandemic is having a huge impact on dermatological practice including the marked reduction of face‐to‐face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID‐19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID‐19 care for patients assistance and new research needs to be addressed. It is not known yet, if skin lesions and derangement of the skin barrier could make it easier for SARS‐CoV‐2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS‐CoV‐2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS‐CoV‐2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID‐19 disaster. Learning from experience may help to cope with future major societal changes.
Authors Safiya Richardson; Jamie S. Hirsch; Mangala Narasimhan, James M. Crawford, Thomas McGinn, Karina W. Davidson
ABSTRACT IMPORTANCE There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). OBJECTIVE To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. DESIGN, SETTING, AND PARTICIPANTS Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. EXPOSURES Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. MAIN OUTCOMES AND MEASURES Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. RESULTS A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/minute, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. Mortality for those requiring mechanical ventilation was 88.1%. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). CONCLUSIONS AND RELEVANCE This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.
Authors Giacomo Spinato, Cristoforo Fabbris, Jerry Polesel, Diego Cazzador, Daniele Borsetto, Claire Hopkins, MA(Oxon),Paolo Boscolo-Rizzo
Authors Xavier Valette, Damien du Cheyron, Suzanne Goursaud
Authors Shufa Zheng, Jian Fan, Fei Yu, Baihuan Feng, Bin Lou, Qianda Zou, Guoliang Xie, Sha Lin, Ruonan Wang, Xianzhi Yang, Weizhen Chen, Qi Wang, Dan Zhang, Yanchao Liu, Renjie Gong, Zhaohui Ma, Siming Lu, Yanyan Xiao, Yaxi Gu, Jinming Zhang, Hangping Yao, Kaijin ,Xiaoyang Lu,Guoqing Wei, Jianying Zhou,Qiang Fang, Hongliu Cai, Yunqing Qiu,Jifang Sheng, Yu Chen, Tingbo Liang
ABSTRACT Objective To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China. Design Retrospective cohort study. Setting A designated hospital for patients with covid-19 in Zhejiang province, China. Participants 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020. Main outcome measures Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed. Results 3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients. Conclusion The duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease. sequentially hospitalized patients with confirmed COVID-19 in the New York City area.
OXFORD UNIVERSITY PRESS
Authors Giuseppe Lippi, Brandon M. Henry
Diabetes, Obesity and Metabolism
Authors Juyi Li, Xiufang Wang, Jian Chen, Xiuran Zuo, Hongmei Zhang, Aiping Deng
Authors Yang Liu, Bei Mao, Shuo Liang, Jia-wei Yang, Hai-wen Lu, Yan-hua Chai, Lan Wang, Li Zhang, Qiu- hong Li, Lan Zhao, Yan He, Xiao-long Gu, Xiao-bin Ji, Li Li, Zhi-jun Jie, Qiang Li, Xiang-yang Li, Hong-zhou Lu, Wen-hong Zhang, Yuan-lin Song, Jie-ming Qu, Jin-fu Xu
Authors Nicola Principi, Susanna Esposito
Authors Pauline Vetter, Diem Lan Vu, Arnaud G L’Huillier, Manuel Schibler, Laurent Kaiser, Frederique Jacquerioz
THE NEW ENGLAND JOUNAL OF MEDICINE
Authors Gianpaolo Toscano, Francesco Palmerini, Sabrina Ravaglia,Luigi Ruiz, Paolo Invernizzi,M. Giovanna Cuzzoni, Fausto Baldanti, Rossana Daturi, Paolo Postorino, Anna Cavallini, Giuseppe Micieli
Authors John B. Moore, Carl H. June
Authors Lian Chen, Qin Li, Danni Zheng, Hai Jiang, M.Yuan Wei
RADIOLOGY
Authors Davide Colombi, Flavio C. Bodini, Marcello Petrini, Gabriele Maffi, Nicola Morell, Gianluca Milanese, Mario Silva, Nicola Sverzellati, Emanuele Michieletti
Background Computed tomography (CT) of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease depicts the extent of lung involvement in COVID-19 pneumonia. Purpose The aim of the study was to determine the value of quantification of the well-aerated lung obtained at baseline chest CT for determining prognosis in patients with COVID-19 pneumonia. Materials and Methods Patients who underwent chest CT suspected for COVID-19 pneumonia at the emergency department admission between February 17 to March 10, 2020 were retrospectively analyzed. Patients with negative reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 in nasal-pharyngeal swabs, negative chest CT, and incomplete clinical data were excluded. CT was analyzed for quantification of well aerated lung visually (%V-WAL) and by open-source software (%S-WAL and absolute volume, VOL-WAL). Clinical parameters included demographics, comorbidities, symptoms and symptom duration, oxygen saturation and laboratory values. Logistic regression was used to evaluate relationship between clinical parameters and CT metrics versus patient outcome (ICU admission/death vs. no ICU admission/ death). The area under the receiver operating characteristic curve (AUC) was calculated to determine model performance. Results The study included 236 patients (females 59/123, 25%; median age, 68 years). A %V-WAL<73% (OR, 5.4; 95% CI, 2.7-10.8; P<0.001), %S-WAL<71% (OR, 3.8; 95% CI, 1.9-7.5; P<0.001), and VOL-WAL<2.9 L (OR, 2.6; 95% CI, 1.2-5.8; P<0.01) were predictors of ICU admission/death. In comparison with clinical model containing only clinical parameters (AUC, 0.83), all three quantitative models showed higher diagnostic performance (AUC 0.86 for all models). The models containing %V-WAL<73% and VOL-WAL<2.9L were superior in terms of performance as compared to the models containing only clinical parameters (P=0.04 for both models). Conclusion In patients with confirmed COVID-19 pneumonia, visual or software quantification the extent of CT lung abnormality were predictors of ICU admission or death. Summary Visual and software-based quantification of well aerated lung parenchyma on admission chest CT were predictors of intensive care unit (ICU) admission or death in patients with COVID-19 pneumonia.
Authors Parag Goyal, Justin J. Choi, Laura C. Pinheiro, Edward J. Schenck, Ruijun Chen, Assem Jabri, Michael J. Satlin, Thomas R. Campion, Musarrat Nahid
CENTERS FOR DISEASE CONTROL AND PREVENTION
Authors Claire Duployez , Rémi Le Guern, Claire Tinez, Anne-Laure Lejeune, Laurent Robriquet, Sophie Six, Caroline Loïez, Frédéric Wallet
Authors Michael S Xydakis, Puya Dehgani-Mobaraki, Eric H Holbrook, Urban W Geisthoff, Christian Bauer, Charlotte Hautefort, Philippe Herman, Geoffrey T Manley, ina M Lyon, Claire Hopkins
Authors François Bénézit, Paul Le Turnier, Charles Declerck, Cécile Paillé, Matthieu Revest, Vincent Dubée, Pierre Tattevin
Authors Piero Boraschi
Authors Julie Helms, Sphane Kremer, Hamid Merdji, Rapha l Clere-Jehl, Malika Schenck, Christine Kummerlen, Olivier Collange,Clotilde Boulay, Samira Fafi-Kremer, Micka Ohana, Mathieu Anheim, Ferhat Meziani
Authors David Kim, James Quinn, Benjamin Pinsky, Nigam H. Shah, Ian Brown
Authors Philip Anfinrud, Valentyn Stadnytskyi, Christina E. Bax, Adriaan Bax
Authors Samuel J. Pleasure, Ari J. Green, S. Andrew Josephson
Authors Luciano Gattinoni, Davide Chiumello, Pietro Caironi, Mattia Busana, Federica Romitti, Luca Brazzi, Luigi Camporota
Authors: Luciano Gattinoni, Davide Chiumello, Pietro Caironi, Mattia Busana, Federica Romitti, Luca Brazzi, Luigi Camporota
Authors Desmond Sutton, Karin Fuchs, Mary D’Alton, Dena Goffman
RESEARCH SQUARE
Authors Andrea Borghesi, Roberto Maroldi
ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus recently isolated from humans. SARS-CoV-2 was discovered to be the pathogen responsible for a cluster of pneumonia associated with severe respiratory disease occurred in December 2019 in China. This novel pulmonary infection, formally called coronavirus disease 2019 (COVID-19), has spread rapidly in China and beyond. On 8 March 2020, the number of Italians with SARS-CoV-2 infection was 7375 with a 48% hospitalization rate. At present, chest computed tomography imaging is considered the most effective method for detection of lung abnormalities in early-stage disease and for quantitative assessment of severity and progression of COVID-19 infection. Although chest x-ray (CXR) is considered not sensitive for the detection of pulmonary involvement in the early stage of disease, we believe that, in the current emergency setting, CXR can be a useful diagnostic tool for monitoring the rapid progression of lung abnormalities in infected patients, particularly in intensive care units. In this article we present our experimental CXR scoring system that we are applying in hospitalized patients with COVID-19 pneumonia to quantify and monitor the severity and progression of this new infectious disease. We also present the results of our preliminary validation study on a sample of 100 hospitalized patients with SARS-CoV-2 infection for whom the final outcome (recovery or death) was available.
Authors Ling Mao, Huijuan Jin, Mengdie Wang, Yu Hu, Shengcai Chen, Quanwei He, Jiang Chang, Candong Hong, AAVV
The New England Journal of Medicine
Authors Mark A. Lewis
Authors TAIT SHAFANETI - JONATHAN RIPP - MICKEY TROCKEL
Authors Louise Aronson
BMJ JOURNAL
Authors Lu Chen, Meizhou Liu, Zheng Zhang, Kun Qiao, Ting Huang, Miaohong Chen, Na Xin, Zuliang Huang, Lei Liu, Guoming Zhang, Jiantao Wang
ABSTRACT Purpose To report the ocular characteristics and the presence of viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens in a patient with confirmed 2019 novel coronavirus disease (COVID-19). Participant and methods A 30-year-old man with confirmed COVID-19 and bilateral acute conjunctivitis which occurred 13 days after illness onset. Based on detailed ophthalmic examination, reverse transcription PCR (RT-PCR) was performed to detect SARS-CoV-2 virus in conjunctival swabs. The ocular characteristics, presence of viral RNA and viral dynamics of SARS-CoV-2 in the conjunctival specimens were evaluated. Results Slit lamp examination showed bilateral acute follicular conjunctivitis. RT-PCR assay demonstrated the presence of viral RNA in conjunctival specimen 13 days after onset (cycle threshold value: 31). The conjunctival swab specimens remained positive for SARS-CoV-2 on 14 and 17 days after onset. On day 19, RT-PCR result was negative for SARS-CoV-2. Conclusion SARS-CoV-2 is capable of causing ocular complications such as viral conjunctivitis in the middle phase of illness. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection. However, conjunctival sampling might not be useful for early diagnosis because the virus may not appear initially in the conjunctiva.
Authors Deborah J. Cook, John C. Marshall, Robert A. Fowler
Authors Giacomo Grasselli, Alberto Zangrillo, Alberto Zanella, Massimo Antonelli, Luca Cabrini, Antonio Castelli, Danilo Cereda
Authors SAAD OMER - PREETI MALANI - CARLOS DEL RIO
Nature Review
Authors T. Alp Ikizler, ùAlan S. Kliger
Authors Giacomo Grasselli, Alberto Zangrillo, Alberto Zanella, Massimo Antonelli, Luca Cabrini, Antonio Castelli, Danilo Cereda,Antonio Coluccello, Giuseppe Foti, Roberto Fumagalli, Giorgio Iotti, Nicola Latronico, Luca Lorini, Stefano Merler,Giuseppe Natalini, Alessandra Piatti, Marco Vito Ranieri, Anna Mara Scandroglio, Enrico Storti, Maurizio Cecconi,Antonio Pesenti
ABSTRACT IMPORTANCE In December 2019, a novel coronavirus (severe acute respiratory syndrome coro- navirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Informa- tion about the clinical characteristics of infected patients who require intensive care is limited. OBJECTIVE To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. EXPOSURES SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. MAIN OUTCOMES AND MEASURES Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. RESULTS Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and FIO2 was greater than 50% in 89% of patients. The median PaO2/FIO2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged 63 years) and older patients (n = 514 aged 64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median FIO2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, −10% [95% CI, −14% to 6%]; P = .006), and median PaO2/FIO2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, −8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower PaO2/FIO2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, −27 [95% CI, −42 to −12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age 64 years) had higher mortality than younger patients (n = 795; age 63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001). CONCLUSIONS AND RELEVANCE In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.
The Journal of Bone & Joint Surgery
Authors Josep Maria Muñoz Vives, Montsant Jornet-Gibert, J. Cámara-Cabrera, Pedro L. Esteban, Laia Brunet, Luis Delgado-Flores, P. Camacho-Carrasco, P. Torner and Francesc Marcano-Fernández
Authors Piva S, Filippini M, Turla F, Cattaneo S, Margola A, De Fulviis S, Nardiello I, Beretta A, Ferrari L, Trotta R, Erbici G, Focà E, Castelli F, Rasulo F, Lanspa MJ, Latronico N
Abstract An ongoing pandemic of COVID-19 that started in Hubei, China has resulted in massive strain on the healthcare infrastructure in Lombardy, Italy. The management of these patients is still evolving. Materials and methods This is a single-center observational cohort study of critically ill patients infected with COVID-19. Bedside clinicians abstracted daily patient data on history, treatment, and short-term course. We describe management and a proposed severity scale for treatment used in this hospital. Results 44 patients were enrolled; with incomplete information on 11. Of the 33 studied patients, 91% were male, median age 64; 88% were overweight or obese. 45% were hypertensive, 12% had been taking an ACE-inhibitor. Noninvasive ventilation was performed on 39% of patients for part or all or their ICU stay with no provider infection. Most patients received antibiotics for pneumonia. Patients also received lopinivir/ritonavir (82%), hydroxychloroquine (79%), and tocilizumab (12%) according to this treatment algorithm. Nine of 10 patients survived their ICU course and were transferred to the floor, with one dying in the ICU. Conclusions ICU patients with COVID-19 frequently have hypertension. Many could be managed with noninvasive ventilation, despite the risk of aerosolization. The use of a severity scale augmented clinician management.
Authors Markus F Neurath
ABSTRACT The current coronavirus pandemic is an ongoing global health crisis due to covid-19, caused by severe acute respiratory syndrome coronavirus 2. Although covid-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to covid-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of covid-19. Here, the current understanding of the pathophysiology of covid-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed
Authors Talha Khan Burki
Authors Timothy P. Hanna, Gerald A. Evans, Christopher M. Booth
Authors Mingxuan Xiea, Qiong Chena
ABSTRACT Background: The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta- coronavirus entitled 2019 novel coronavirus (2019-nCoV), has become a global threat. Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions. Methods: Based on recently published literature, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Results: The genome of 2019-nCoV partially resembled SARS-CoV and MERS-CoV, and indicated a bat origin. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Clinical presentation and pathology of COVID-19 greatly resembled SARS and MERS, with less upper respiratory and gastrointestinal symptoms, and more exudative lesions in post-mortems. Potential treatments included remdesivir, chloroquine, tocilizumab, convalescent plasma and vaccine immuniza- tion (when possible). Conclusion: The initial experience from the current pandemic and lessons from the previous two pandemics can help improve future preparedness plans and combat disease progression.
Authors Huali Wang, Tao Li, Paola Barbarino, Serge Gauthier, Henry Brodaty, José Luis Molinuevo, Hengge Xie, Yongan Sun, Enyan Yu, Yanqing Tang, Wendy Weidner, Xin Yu, Show less
Authors Robert O. Bonow, Gregg C. Fonarow, Patrick T.O’Gara, Clyde W. Yancy
Authors Mohammad Madjid, Payam Safavi-Naeini, Scott D. Solomon, Orly Vardeny, Pharm
IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system. OBSERVATIONS Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality. CONCLUSIONS AND RELEVANCE Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.
Authors Riccardo M. Inciardi, Laura Lupi, Gregorio Zaccone, Leonardo Italia, Michela Raffo, Daniela Tomasoni, Dario S. Cani, Manuel Cerini, Davide Farina, Emanuele Gavazzi, Roberto Maroldi, Marianna Adamo, Enrico Ammirati, Gianfranco Sinagra, Carlo M. Lombardi, Marco Metra
ABSTRACT IMPORTANCE Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVE To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. DESIGN, SETTING, AND PARTICIPANT This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. EXPOSURE Cardiac involvement with COVID-19. MAIN OUTCOMES AND MEASURES Detection of cardiac involvement with an increase in levels of N-terminal pro–brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. RESULTS An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase– polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. CONCLUSIONS AND RELEVANCE This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.
Authors Tao Guo, Yongzhen Fan, Ming Chen, Xiaoyan Wu, Lin Zhang, Tao He, Hairong Wang, Jing Wan, Xinghuan Wang, Zhibing Lu
ABSTRACT IMPORTANCE Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce. OBJECTIVE To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020. MAIN OUTCOMES AND MEASURES Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels. RESULT Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro–brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001). Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16). During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (41 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels. The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 25.6% (43 of 168). CONCLUSIONS AND RELEVANCE Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.
Authors Andrea Giacomelli, Laura Pezzati, Federico Conti, Dario Bernacchia, Matteo Siano, Letizia Oreni, Stefano Rusconi, Cristina Gervasoni, Anna Lisa Ridolfo, Giuliano Rizzardini, Spinello Antinori, Massimo Galli
the BMJ
Authors Neil Greenberg, Mary Docherty , Sam Gnanapragasam, Simon Wessely
Authors David W. Kimberlin, Sergio Stagno
Authors Luca Perico, Ariela Benigni, Giuseppe Remuzzi
Authors Xiaoxia Lu, Liqiong Zhang, Hui Du, Jingjing Zhang, Yuan Y. Li, Jingyu Qu, Wenxin Zhang, Youjie Wang, Shuangshuang Bao, Ying Li, Chuansha Wu, Hongxiu Liu, Di Liu, Jianbo Shao, Xuehua Peng, Yonghong Yang, hisheng Liu, Yun Xiang, Furong Zhang, Rona M. Silva, Kent E. Pinkerton, Kunling Shen, Han Xiao, Shunqing Xu, Gary W.K. Wong
ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.
Springer
Authors Livio Luzi, Maria Grazia Radaelli
ABSTRACT Aims Analyze the relationship between obesity and infuenza. Methods Basal hormone milieu, defective response of both innate and adaptive immune system and sedentariness are major determinants in the severity of infuenza viral infection in obese patients. Being overweight not only increases the risk of infection and of complications for the single obese person, but a large prevalence of obese individuals within the popula- tion might increase the chance of appearance of more virulent viral strain, prolongs the virus shedding throughout the total population and eventually might increase overall mortality rate of an infuenza pandemic. Results Waiting for the development of a vaccination against COVID-19, isolation of positive cases and social distancing are the primary interventions. Nonetheless, evidence from previous infuenza pandemics suggests the following interven- tions aimed at improving immune response: (1) lose weight with a mild caloric restriction; (2) include AMPK activators and PPAR gamma activators in the drug treatment for obesity associated with diabetes; and (3) practice mild-to-moderate physical exercise. Conclusions Due to prolonged viral shedding, quarantine in obese subjects should likely be longer than nor mal weight individuals. Keywords Obese subjects / COVID-19 / Infuenza / Immune-modulation
Authors Shaoqing Lei, Fang Jiang, Wating Su, Chang Chen, Jingli Chen, Wei Mei, Li-Ying Zhan, Yifan Jia, Liangqing Zhang, Danyong Liu, Zhong-Yuan Xia, Zhengyuan Xia
ABSTRACT Background: The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were uninten- tionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes. Methods: We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020. Findings: Of the 34 operative patients, the median age was 55 years (IQR, 4363), and 20 (58¢8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 [91¢2%]), fatigue (25 [73¢5%]) and dry cough (18 [52¢9%]). 15 (44¢1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20¢5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury. Interpretation: In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44¢1%) patients needed ICU care, and the mortality rate was 20¢5%. Funding: National Natural Science Foundation of China.
The Lancet Journal
Authors Paul Weiss, David R Murdoch
Authors Tao Chen, Di Wu, Huilong Chen, Weiming Yan, Danlei Yang, Guang Chen, Ke Ma, Dong Xu, Haijing Yu, Hongwu Wang, Tao Wang, Wei Guo, Jia Chen, Chen Ding, Xiaoping Zhang, Jiaquan Huang, Meifang Han, Shusheng Li, Xiaoping Luo, Jianping Zhao, Qin Ning
ABSTRACT OBJECTIVE To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. DESIGN Retrospective case series. SETTING Tongji Hospital in Wuhan, China. PARTICIPANTS Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. MAIN OUTCOME MEASURES Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. RESULTS The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. CONCLUSION Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.
Oxford University Press
Authors Pingzheng Mo, Yuanyuan Xing, Yu Xiao, Liping Deng, Qiu Zhao, Hongling Wang, Yong Xiong, Zhenshun Cheng, Shicheng Gao, Ke Liang, Mingqi Luo, Tielong Chen, Shihui Song, Zhiyong Ma, Xiaoping Chen, Ruiying Zheng, Qian Cao, Fan Wang, Yongxi Zhang
Background: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. Methods: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1st to February 5th. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared. Results: Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P<0.05). Refractory COVID-19 patients were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment including corticosteroid, antiviral drugs and immune enhancer (P<0.05). After adjustment, those with refractory COVID-19 were also more likely to have a male sex and manifestations of anorexia and fever on admission, and receive oxygen, expectorant and adjunctive agents (P<0.05) when considering the factors of disease severity on admission, mechanical ventilation, and ICU transfer. Conclusion: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy.
COVID-19, SARS-CoV-2, clinical efficacy, predictors
Authors David Baud, Xiaolong Qi, Karin Nielsen-Saines, Didier Musso, Léo Pomar, Guillaume Favre
The Lancet Journal<
Authors Hans-Christian Thorsen-Meyer, Annelaura B Nielsen, Anna P Nielsen, Benjamin Skov Kaas-Hansen, Palle Toft, Jens Schierbeck, Thomas Strøm, Piotr J Chmura, Marc Heimann, Lars Dybdahl, Lasse Spangsege, Patrick Hulsen, Kirstine Belling, Søren Brunak, Anders Perner
Background Many mortality prediction models have been developed for patients in intensive care units (ICUs); most are based on data available at ICU admission. We investigated whether machine learning methods using analyses of time-series data improved mortality prognostication for patients in the ICU by providing real-time predictions of 90-day mortality. In addition, we examined to what extent such a dynamic model could be made interpretable by quantifying and visualising the features that drive the predictions at different timepoints. Methods Based on the Simplified Acute Physiology Score (SAPS) III variables, we trained a machine learning model on longitudinal data from patients admitted to four ICUs in the Capital Region, Denmark, between 2011 and 2016. We included all patients older than 16 years of age, with an ICU stay lasting more than 1 h, and who had a Danish civil registration number to enable 90-day follow-up. We leveraged static data and physiological time-series data from electronic health records and the Danish National Patient Registry. A recurrent neural network was trained with a temporal resolution of 1 h. The model was internally validated using the holdout method with 20% of the training dataset and externally validated using previously unseen data from a fifth hospital in Denmark. Its performance was assessed with the Matthews correlation coefficient (MCC) and area under the receiver operating characteristic curve (AUROC) as metrics, using bootstrapping with 1000 samples with replacement to construct 95% CIs. A Shapley additive explanations algorithm was applied to the prediction model to obtain explanations of the features that drive patient-specific predictions, and the contributions of each of the 44 features in the model were analysed and compared with the variables in the original SAPS III model. Findings From a dataset containing 15615 ICU admissions of 12616 patients, we included 14190 admissions of 11492 patients in our analysis. Overall, 90-day mortality was 33⋅1% (3802 patients). The deep learning model showed a predictive performance on the holdout testing dataset that improved over the timecourse of an ICU stay: MCC 0⋅29 (95% CI 0⋅25–0⋅33) and AUROC 0⋅73 (0⋅71–0⋅74) at admission, 0⋅43 (0⋅40–0⋅47) and 0⋅82 (0⋅80–0⋅84) after 24 h, 0⋅50 (0⋅46–0⋅53) and 0⋅85 (0⋅84–0⋅87) after 72 h, and 0⋅57 (0⋅54–0⋅60) and 0⋅88 (0⋅87–0⋅89) at the time of discharge. The model exhibited good calibration properties. These results were validated in an external validation cohort of 5827 patients with 6748 admissions: MCC 0⋅29 (95% CI 0⋅27–0⋅32) and AUROC 0⋅75 (0⋅73–0⋅76) at admission, 0⋅41 (0⋅39–0⋅44) and 0⋅80 (0⋅79–0⋅81) after 24 h, 0⋅46 (0⋅43–0⋅48) and 0⋅82 (0⋅81–0⋅83) after 72 h, and 0⋅47 (0⋅44–0⋅49) and 0⋅83 (0⋅82–0⋅84) at the time of discharge. Interpretation The prediction of 90-day mortality improved with 1-h sampling intervals during the ICU stay. The dynamic risk prediction can also be explained for an individual patient, visualising the features contributing to the prediction at any point in time. This explanation allows the clinician to determine whether there are elements in the current patient state and care that are potentially actionable, thus making the model suitable for further validation as a clinical tool. Funding Novo Nordisk Foundation and the Innovation Fund Denmark.
Authors Isaac Ghinai, Tristan D McPherson, Jennifer C Hunter, Hannah L Kirking, Demian Christiansen, Kiran Joshi, Rachel Rubin, Shirley Morales-Estrada, Stephanie R Black, Massimo Pacilli, Marielle J Fricchione, Rashmi K Chugh, Kelly A Walblay, N Seema Ahmed, William C Stoecker, Nausheen F Hasan, Deborah P Burdsall, Heather E Reese, Megan Wallace, Chen Wang, Darcie Moeller, Jacqueline Korpics, Shannon A Novosad, Isaac Benowitz, Max W Jacobs, Vishal S Dasari, Megan T Patel, Judy Kauerauf, E Matt Charles, Ngozi O Ezike, Victoria Chu, Claire M Midgley, Melissa A Rolfes, Susan I Gerber, Xiaoyan Lu, Stephen Lindstrom, Jennifer R Verani, Jennifer E Layden
Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. Methods Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient’s symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. Findings Patient 1—a woman in her 60s—returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. Interpretation Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected.
Authors Hua Cai
Authors Lei Fang, George Karakiulakis, Michael Roth
Authors Fei Zhou, Ting Yu, Ronghui Du, Guohui Fan, Ying Liu, Zhibo Liu, Jie Xiang, Yeming Wang, Bin Song, Xiaoying Gu, Lulu Guan, Yuan Wei, Hui Li, Xudong Wu, Jiuyang Xu, Shengjin Tu, Yi Zhang, Hua Chen, Bin Cao
Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory- confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
Authors Zachary T. Bloomgarden
Authors Ren Mao, Jie Liang, Jun Shen, Subrata Ghosh, Liang-Ru Zhu, Hong Yang, Kai-Chun Wu, Min-Hu Chen
Authors Tianbing Wang, Zhe Du, Fengxue Zhu, Zhaolong Cao, Youzhong An, Yan Gao, Baoguo Jiang
Authors Ying-Ying Zheng, Yi-Tong Ma, Jin-Ying Zhang, Xiang Xie
The Journal of Infection in Developing Countries
Authors Rossella Porcheddu, Caterina Serra, David Kelvin, Nikki Kelvin, Salvatore Rubino
As of 28 February 2020, Italy had 888 cases of SARS-CoV-2 infections, with most cases in Northern Italy in the Lombardia and Veneto regions. Travel-related cases were the main source of COVID-19 cases during the early stages of the current epidemic in Italy. The month of February, however, has been dominated by two large clusters of outbreaks in Northern Italy, south of Milan, with mainly local transmission the source of infections. Contact tracing has failed to identify patient zero in one of the outbreaks. As of 28 February 2020, twenty-one cases of COVID-19 have died. Comparison between case fatality rates in China and Italy are identical at 2.3. Additionally, deaths are similar in both countries with fatalities in mostly the elderly with known comorbidities. It will be important to develop point-of-care devices to aid clinicians in stratifying elderly patients as early as possible to determine the potential level of care they will require to improve their chances of survival from COVID-19 disease.
Novel coronavirus COVID-19, outbreak, Italy, Case Fatality Rates SARS-CoV-19
Radiology Society of North America
Authors Tao Ai MD, Zhenlu Yang, Hongyan Hou, Chenao Zhan, Chong Chen, Wenzhi Lv, Qian Tao, Ziyong Sun, Liming Xia
Background: Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests. Purpose: To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19. Methods From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more. Results Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative. Conclusion Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas.
2019-nCoV pneumonia,reverse transcription polymerase chain reaction, chest CT imaging, diagnostic value, positive rate
Science Direct
Authors Chih-Cheng Lai, Yen Hung Liu, Cheng-Yi Wang, Ya-Hui Wang, Shun-Chung Hsueh, Muh-Yen Yen, Wen-Chien Ko, Po-Ren Hsueh
ABSTRACT Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneu- monia. Adults represent the population with the highest infection rate; however, neonates,children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymp- tomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treat- ment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.
Authors Pengfei Sun, Xiaosheng Lu, Chao Xu, Wenjuan Sun, Bo Pan
Since December 2019, a series of unexplained pneumonia cases have been reported in Wuhan, China. On 12 January 2020, the World Health Organization (WHO) temporarily named this new virus as the 2019 novel coronavirus (2019‐nCoV). On 11 February 2020, the WHO officially named the disease caused by the 2019‐nCoV as coronavirus disease (COVID‐19). The COVID‐19 epidemic is spreading all over the world, especially in China. Based on the published evidence, we systematically discuss the characteristics of COVID‐19 in the hope of providing a reference for future studies and help for the pre- vention and control of the COVID‐19 epidemic.
2019‐nCoV, coronavirus, COVID‐19, epidemiology, pneumonia, SARS‐CoV‐2
Authors Fabrizio Albarello, Elisa Pianura, Federica Di Stefano, Massimo Cristofaro, Ada Petrone, Luisa Marchioni, Claudia Palazzolo, Vincenzo Schininà, Emanuele Nicastri, Nicola Petrosillo, Paolo Campioni, Petersen Eskild, Alimuddin Zumla, Giuseppe Ippolito
Introduction: Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients. Objective: We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS). Results: Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes. Conclusions: Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment.
International Journal of Infectious Diseases
Authors Hiroshi Nishiura, Tetsuro Kobayashi, Ayako Suzuki, Sung-Mok Jung, Katsuma Hayashi, Ryo Kinoshita, Yichi Yang, Baoyin Yuan, Andrei R. Akhmetzhanov, Natalie M. Linton
Authors Xingzhi Xie, Zheng Zhong ,Wei Zhao, Chao Zheng, Fei Wang, Jun Liu
Some patients with positive chest CT findings may present with negative results of real time reverse-transcription–polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening
Authors Alexander E. Merkler, Neal S. Parikh, Saad Mir, Ajay Gupta, Hooman Kamel, Eaton Lin, Joshua Lantos, Edward J. Schenck, Parag Goyal, Samuel S. Bruce, Joshua Kahan, Kelsey N. Lansdale, Natalie M. LeMoss, Santosh B. Murthy, Philip E. Stieg, Matthew E. Fink, Costantino Iadecola, Alan Z. Segal, Marika Cusick, Thomas R. Campion Jr, Ivan Diaz, Cenai Zhang, Babak B. Navi
ABSTRACT Importance It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. Objective To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. Design, Setting, and Participants This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). Exposures COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. Main Outcomes and Measures A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. Results Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. Conclusions and Relevance In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.
Authors Timothy M Rawson, Luke S P Moore, Nina Zhu, Nishanthy Ranganathan, Keira Skolimowska, Mark Gilchrist, Giovanni Satta, Graham Cooke, Alison Holmes
ABSTRACT Background: To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection. Methods: MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed. Results: 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. Conclusions: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently required. Keywords: SARS-COV-2, antimicrobial stewardship, antimicrobial resistance
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