Immunology

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08/01/2021 Articles
T resident helper cells promote humoral responses in the lung

SCIENCE IMMUNOLOGY

Authors
Nivedya Swarnalekha, David Schreiner, Ludivine C. Litzler, Saadia Iftikhar, Daniel Kirchmeier, Marco Künzli, Young Min Son, Jie Sun, Etori Aguiar Moreira, Carolyn G. King

Abstract
Influenza is a deadly and costly infectious disease, even during flu seasons when an effective vaccine has been developed. To improve vaccines against respiratory viruses, a better understanding of the immune response at the site of infection is crucial. After influenza infection, clonally expanded T cells take up permanent residence in the lung, poised to rapidly respond to subsequent infection. Here, we characterized the dynamics and transcriptional regulation of lung-resident CD4+ T cells during influenza infection and identified a long-lived, Bcl6-dependent population that we have termed T resident helper (TRH) cells. TRH cells arise in the lung independently of lymph node T follicular helper cells but are dependent on B cells, with which they tightly colocalize in inducible bronchus-associated lymphoid tissue (iBALT). Deletion of Bcl6 in CD4+ T cells before heterotypic challenge infection resulted in redistribution of CD4+ T cells outside of iBALT areas and impaired local antibody production. These results highlight iBALT as a homeostatic niche for TRH cells and advocate for vaccination strategies that induce TRH cells in the lung.

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04/01/2021 Articles
Neutralizing antibody titres in SARS-CoV-2 infections

NATURE

Authors
Eric H. Y. Lau, Owen T. Y. Tsang, David S. C. Hui, Mike Y. W. Kwan, Wai-hung Chan, Susan S. Chiu, Ronald L. W. Ko, Kin H. Chan, Samuel M. S. Cheng, Ranawaka A. P. M. Perera, Benjamin J. Cowling, Leo L. M. Poon, Malik Peiris

Abstract
The SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT90) and 50% (PRNT50) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT50 titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT50 antibody titres to decrease by half (T1/2) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT90 and PRNT50 antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.

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23/12/2020 Articles
Discordant neutralizing antibody and T cell responses in asymptomatic ...

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

SCIENCE IMMUNOLOGY

Authors
Catherine J. Reynolds, Leo Swadling, Joseph M. Gibbons, Corinna Pade, Melanie P. Jensen, Mariana O. Diniz, Nathalie M. Schmidt, David K. Butler, Oliver E. Amin, Sasha N. L. Bailey, Sam M. Murray, Franziska P. Pieper, Stephen Taylor, Jessica Jones, Meleri Jones, Wing-Yiu Jason Lee, Joshua Rosenheim, Aneesh Chandran, George Joy, Cecilia Di Genova, Nigel Temperton, Jonathan Lambourne, Teresa Cutino-Moguel, Mervyn Andiapen, Marianna Fontana, Angelique Smit, Amanda Semper, Ben O’Brien, Benjamin Chain, Tim Brooks, Charlotte Manisty, Thomas Treibel, James C. Moon, Mahdad Noursadeghi, Daniel M. Altmann, Mala K. Maini, Áine McKnight, Rosemary J. Boyton

Abstract
Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.

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22/12/2020 Report
Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucl...

Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence

SCIENCE IMMUNOLOGY

Authors
Gemma E. Hartley, Emily S.J. Edwards, Pei M. Aui, Nirupama Varese, Stephanie Stojanovic, James McMahon, Anton Y. Peleg, Irene Boo, Heidi E. Drummer, P. Mark Hogarth, Robyn E. O’Hehir, Menno C. van Zelm

Abstract
Lasting immunity following SARS-CoV-2 infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Therefore, we generated fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP) to determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. A total of 36 blood samples were obtained from 25 COVID-19 patients between 4 and 242 days post-symptom onset including 11 paired samples. While serum IgG to RBD and NCP was identified in all patients, antibody levels began declining at 20 days post-symptom onset. RBD- and NCP-specific Bmem cells predominantly expressed IgM+ or IgG1+ and continued to rise until 150 days. RBD-specific IgG+ Bmem were predominantly CD27+, and numbers significantly correlated with circulating follicular helper T cell numbers. Thus, the SARS-CoV-2 antibody response contracts in convalescence with persistence of RBD- and NCP-specific Bmem cells. Flow cytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term immune memory following infection or vaccination for COVID-19.

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22/12/2020 Original Investigation
Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacen...

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic

JAMA

Authors
Andrea G. Edlow, Jonathan Z. Li, Ai-ris Y. Collier, Caroline Atyeo, Kaitlyn E. James, Adeline A. Boatin, Kathryn J. Gray, Evan A. Bordt, Lydia L. Shook, Lael M. Yonker, Alessio Fasano, Khady Diouf, Natalie Croul, Samantha Devane, Laura J. Yockey, Rosiane Lima, Jessica Shui, Juan D. Matute, Paul H. Lerou, Babatunde O. Akinwunmi, Aaron Schmidt, Jared Feldman, Blake M. Hauser, Timothy M. Caradonna, Denis De la Flor, Paolo D’Avino, James Regan, Heather Corry, Kendyll Coxen, Jesse Fajnzylber, David Pepin, Michael S. Seaman, Dan H. Barouch, Bruce D. Walker, Xu G. Yu, Anjali J. Kaimal, Drucilla J. Roberts, Galit Alter

Abstract
Importance Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Objective To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti–SARS-CoV-2 antibody, and incidence of fetoplacental infection.

Design, Setting, and Participants This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription–polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2.

Exposures SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR.

Main Outcomes and Measures The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti–SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta.

Results Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti–receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti–SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti–receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted.

Conclusions and Relevance In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

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21/12/2020 Articles
Multiplex assays for the identification of serological signatures of S...

Multiplex assays for the identification of serological signatures of SARS-CoV-2 infection: an antibody-based diagnostic and machine learning study

THE LANCET

Authors
Jason Rosado, Stéphane Pelleau, Charlotte Cockram, Sarah Hélène Merkling, Narimane Nekkab, Caroline Demeret, Annalisa Meola, Solen Kerneis, Benjamin Terrier, Samira Fafi-Kremer, Jerome de Seze, Timothée Bruel, François Dejardin, Stéphane Petres, Rhea Longley, Arnaud Fontanet, Marija Backovic, Ivo Mueller, Michael T White

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17/12/2020 Comment
Persistence of IgG response to SARS-CoV-2

THE LANCET

Authors
Els Duysburgh Laure Mortgat Cyril Barbezange Katelijne Dierick Natalie Fischer Leo Heyndrickx Veronik Hutse Isabelle Thomas Steven Van Gucht Bea Vuylsteke Kevin Arien Isabelle Desombere

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15/12/2020 Research
Antibodies and T cells protect against SARS-CoV-2

NIH (NATIONAL INSTITUTE OF HEALTH)

Authors
Sharon Reynolds

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30/11/2020 Articles
Depletion of circulating IgM memory B cells predicts unfavourable outc...

Depletion of circulating IgM memory B cells predicts unfavourable outcome in COVID-19

NATURE

Authors
Marco Vincenzo Lenti, Nicola Aronico, Ivan Pellegrino, Emanuela Boveri, Paolo Giuffrida, Federica Borrelli de Andreis, Patrizia Morbini, Laura Vanelli, Alessandra Pasini, Cristina Ubezio, Federica Melazzini, Alessandro Rascaroli, Valentina Antoci, Stefania Merli, Francesco Di Terlizzi, Umberto Sabatini, Ginevra Cambiè, Annamaria Tenore, Cristina Picone, Alessandro Vanoli, Luca Arcaini, Fausto Baldanti, Marco Paulli, Gino Roberto Corazza, Antonio Di Sabatino

Abstract
Impaired immune responses have been hypothesised to be a possible trigger of unfavourable outcomes in coronavirus disease 2019 (COVID-19). We aimed to characterise IgM memory B cells in patients with COVID-19 admitted to an internal medicine ward in Northern Italy. Overall, 66 COVID-19 patients (mean age 74 ± 16.6 years; 29 females) were enrolled. Three patients (4.5%; 1 female) had been splenectomised and were excluded from further analyses. Fifty-five patients (87.3%) had IgM memory B cell depletion, and 18 (28.6%) died during hospitalisation (cumulative incidence rate 9.26/100 person-week; 5.8–14.7 95% CI). All patients who died had IgM memory B cell depletion. A superimposed infection was found in 6 patients (9.5%), all of them having IgM memory B cell depletion (cumulative incidence rate 3.08/100 person-week; 1.3–6.8 95% CI). At bivariable analyses, older age, sex, number of comorbidities, and peripheral blood lymphocyte count < 1500/µl were not correlated with IgM memory B cell depletion. A discrete-to-marked reduction of the B-cell compartment was also noticed in autoptic spleen specimens of two COVID-19 patients. We conclude that IgM memory B cells are commonly depleted in COVID-19 patients and this correlates with increased mortality and superimposed infections.

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12/11/2020 Rapid Communication
Convalescent plasma for COVID-19: male gender, older age and hospitali...

Convalescent plasma for COVID-19: male gender, older age and hospitalisation associated with high neutralising antibody levels, England, 22 April to 12 May 2020

EUROSURVEILLANCE

Authors
Jennifer Mehew, Rachel Johnson, David Roberts, Heli Harvala

ABSTRACT
We analysed factors associated with neutralising antibody levels in 330 convalescent plasma donors. Women and younger donors were more likely not to have measurable neutralising antibodies, while higher antibody levels were observed in men, in older donors and in those who had been hospitalised. These data will be of value in the timely recruitment of convalescent plasma donors most likely to have high levels of neutralising antibodies for ongoing studies investigating its effectiveness.

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06/11/2020 Report
Preexisting and de novo humoral immunity to SARS-CoV-2 in humans

SCIENCE

Authors
Kevin W. Ng, Georgina H. Cornish, Annachiara Rosa, Ruth Harvey, Saira Hussain, Rachel Ulferts, Christopher Earl, Antoni G. Wrobel,Donald J. Benton, Chloe Roustan, William Bolland, Rachael Thompson, Ana Agua-Doce, Philip Hobson, Judith Heaney, Hannah Rickman, Stavroula Paraskevopoulou, Catherine F. Houlihan, Kirsty Thomson, Emilie Sanchez, Gee Yen Shin, Moira J. Spyer,Dhira Joshi, Nicola O’Reilly, Philip A. Walker,Svend Kjaer, Andrew Riddell, Catherine Moore, Bethany R. Jebson, Meredyth Wilkinson, Lucy R. Marshall, Elizabeth C. Rosser, Anna Radziszewska, Hannah Peckham, Coziana Ciurtin, Lucy R. Wedderburn, Rupert Beale, Charles Swanton, Sonia Gandhi, Brigitta Stockinger, John McCauley, Steve J. Gamblin, Laura E. McCoy, Peter Cherepanov, Eleni Nastouli, George Kassiotis

Abstract
Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detect preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)-reactive antibodies were detectable by a flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the IgG class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.

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05/11/2020 Articles
T Cell Responses to Coronavirus Infection are Complicated

VIROLOGY BLOG

Authors
Gertrud U. Rey

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05/11/2020 Letter
Distinct antibody responses to SARS-CoV-2 in children and adults acros...

Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum

NATURE

Authors
Stuart P. Weisberg, Thomas J. Connors, Yun Zhu, Matthew R. Baldwin, Wen-Hsuan Lin, Sandeep Wontakal, Peter A. Szabo, Steven B. Wells, Pranay Dogra, Joshua Gray, Emma Idzikowski, Debora Stelitano, Francesca T. Bovier, Julia Davis-Porada, Rei Matsumoto, Maya Meimei Li Poon, Michael Chait, Cyrille Mathieu, Branka Horvat, Didier Decimo, Krystalyn E. Hudson, Flavia Dei Zotti, Zachary C. Bitan, Francesca La Carpia, Stephen A. Ferrara, Emily Mace, Joshua Milner, Anne Moscona, Eldad Hod, Matteo Porotto, Donna L. Farber

Abstract
Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3,4,5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.

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03/11/2020 Articles
Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production

CELL

Authors
Yuezhou Chen, Adam Zuiani, Stephanie Fischinger, Douglas A. Lauffenburger, Galit Alter, Duane R. Wesemann

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02/11/2020 News
Covid-19: T cell response lasts for at least six months after infectio...

Covid-19: T cell response lasts for at least six months after infection, study shows

THE BMJ

Authors
Jacqui Wise

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02/11/2020 Articles
SARS-CoV-2 seroprevalence and transmission risk factors among high-ris...

SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study

THE LANCET

Authors
Oon Tek Ng, Kalisvar Marimuthu, Vanessa Koh, Junxiong Pang, Kyaw Zaw Linn, Jie Sun, Liang De Wang, Wan Ni Chia, Charles Tiu, Monica Chan, Li Min Ling, Shawn Vasoo, Mohammad Yazid Abdad, Po Ying Chia, Tau Hong Lee, Ray Junhao Lin, Sapna P Sadarangani, Mark I-Cheng Chen, Zubaidah Said, Lalitha Kurupatham, Rachael Pung, Lin-Fa Wang, Alex R Cook, Yee-Sin Leo, Vernon JM Lee

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28/10/2020 Articles
SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-1...

SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Peter Chen, Ajay Nirula, Barry Heller, Robert L. Gottlieb, Joseph Boscia, Jason Morris, Gregory Huhn, Jose Cardona, Bharat Mocherla, Valentina Stosor, Imad Shawa, Andrew C. Adams, Jacob Van Naarden, Kenneth L. Custer, Lei Shen, Michael Durante, Gerard Oakley, Andrew E. Schade, Janelle Sabo, Dipak R. Patel, Paul Klekotka, Daniel M. Skovronsky

Abstract
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19), which is most frequently mild yet can be severe and life-threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral load, ameliorate symptoms, and prevent hospitalization.

METHODS
In this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. The primary outcome was the change from baseline in the viral load at day 11. The results of a preplanned interim analysis as of September 5, 2020, are reported here.

RESULTS
At the time of the interim analysis, the observed mean decrease from baseline in the log viral load for the entire population was −3.81, for an elimination of more than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was −0.53 (95% confidence interval [CI], −0.98 to −0.08; P=0.02), for a viral load that was lower by a factor of 3.4. Smaller differences from placebo in the change from baseline were observed among the patients who received the 700-mg dose (−0.20; 95% CI, −0.66 to 0.25; P=0.38) or the 7000-mg dose (0.09; 95% CI, −0.37 to 0.55; P=0.70). On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. The percentage of patients who had a Covid-19–related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group.

CONCLUSIONS
In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501. opens in new tab.)

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28/10/2020 Report
Robust neutralizing antibodies to SARS-CoV-2 infection persist for mon...

Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

SCIENCE

Authors
Ania Wajnberg, Fatima Amanat, Adolfo Firpo, Deena R. Altman, Mark J. Bailey, Mayce Mansour, Meagan McMahon, Philip Meade, Damodara Rao Mendu, Kimberly Muellers, Daniel Stadlbauer, Kimberly Stone, Shirin Strohmeier, Viviana Simon, Judith Aberg, David L. Reich, Florian Krammer, Carlos Cordon-Cardo

Abstract
SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City. We also show that titers are relatively stable for at least a period approximating 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses. These titers remain relatively stable for several months after infection.

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26/10/2020 Articles
Longitudinal observation and decline of neutralizing antibody response...

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

NATURE

Authors
Jeffrey Seow, Carl Graham, Blair Merrick, Sam Acors, Suzanne Pickering, Kathryn J. A. Steel, Oliver Hemmings, Aoife O’Byrne, Neophytos Kouphou, Rui Pedro Galao, Gilberto Betancor, Harry D. Wilson, Adrian W. Signell, Helena Winstone, Claire Kerridge, Isabella Huettner, Jose M. Jimenez-Guardeño, Maria Jose Lista, Nigel Temperton, Luke B. Snell, Karen Bisnauthsing, Amelia Moore, Adrian Green, Lauren Martinez, Brielle Stokes, Johanna Honey, Alba Izquierdo-Barras, Gill Arbane, Amita Patel, Mark Kia Ik Tan, Lorcan O’Connell, Geraldine O’Hara, Eithne MacMahon, Sam Douthwaite, Gaia Nebbia, Rahul Batra, Rocio Martinez-Nunez, Manu Shankar-Hari, Jonathan D. Edgeworth, Stuart J. D. Neil, Michael H. Malim, Katie J. Doores

Abstract
Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.

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20/10/2020 PRE PUBLICATIONS RELEASE
Systemic and mucosal antibody responses specific to SARS-CoV-2 during ...

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Authors
Carlo Cervia, Jakob Nilsson, Yves Zurbuchen, Alan Valaperti, Jens Schreiner, Aline Wolfensberger, Miro E. Raeber, Sarah Adamo, Sebastian Weigang, Marc Emmenegger, Sara Hasler, Philipp P. Bosshard, Elena De Cecco, Esther Bächli, Alain Rudiger, Melina Stüssi-Helbling, Lars C. Huber, Annelies S. Zinkernagel, Dominik J. Schaer, Adriano Aguzzi, Georg Kochs, Ulrike Held, Elsbeth Probst-Müller, Silvana K. Rampini, Onur Boyman

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19/10/2020 Research
Impaired natural killer cell counts and cytolytic activity in patients...

Impaired natural killer cell counts and cytolytic activity in patients with severe COVID-19

ASH PUBLICATIONS

Authors
Mohammed Osman, Rehan M. Faridi, Wendy Sligl, Meer-Taher Shabani-Rad, Poonam Dharmani-Khan, Arabesque Parker, Amit Kalra, Minal Borkar Tripathi, Jan Storek, Jan Willem Cohen Tervaert, Faisal M. Khan

Abstract
The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–driven coronavirus disease 2019 (COVID-19) has caused unprecedented human death and has seriously threatened the global economy. Early data suggest a surge in proinflammatory cytokines in patients with severe COVID-19, which has been associated with poor outcomes. We recently postulated that the inflammatory response in patients with severe COVID-19 disease is not inhibited by natural killer (NK) cells, resulting in a “cytokine storm.” Here, we assessed the NK-cell functional activity and the associated cytokines and soluble mediators in hospitalized COVID-19 patients. Significantly impaired NK-cell counts and cytolytic activity were observed in COVID-19 patients when compared with healthy controls. Also, cytokines like interleukin 12 (IL12), IL15, and IL21 that are important for NK-cell activity were not detected systematically. Serum concentrations of soluble CD25 (sCD25)/soluble IL2 receptor α (sIL2-Rα) were significantly elevated and were inversely correlated with the percentage of NK cells. Impaired NK-cell cytolytic activity together with other laboratory trends including elevated sCD25 were consistent with a hyperinflammatory state in keeping with macrophage-activation syndrome. Our findings suggest that impaired counts and cytolytic activity of NK cells are important characteristics of severe COVID-19 and can potentially facilitate strategies for immunomodulatory therapies.

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12/10/2020 Articles
THE ASSOCIATION OF IL-6 VALUE, INTERLEUKIN INHIBITORS, AND OUTCOMES OF...

THE ASSOCIATION OF IL-6 VALUE, INTERLEUKIN INHIBITORS, AND OUTCOMES OF PATIENTS WITH COVID-19 IN NEW YORK CITY

SCIENCE

Authors
Reiichiro Obata, Tetsuro Maeda, Dahlia Rizk, Toshik iKuno

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12/10/2020 Comment
What reinfections mean for COVID-19

THE LANCET

Authors
Akiko Iwasaki

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12/10/2020 Articles
Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor ex...

Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium

NATURE

Authors
Satria P. Sajuthi, Peter DeFord, Yingchun Li, Nathan D. Jackson, Michael T. Montgomery, Jamie L. Everman, Cydney L. Rios, Elmar Pruesse, James D. Nolin, Elizabeth G. Plender, Michael E. Wechsler, Angel C. Y. Mak, Celeste Eng, Sandra Salazar, Vivian Medina, Eric M. Wohlford, Scott Huntsman, Deborah A. Nickerson, Soren Germer, Michael C. Zody, Gonçalo Abecasis, Hyun Min Kang, Kenneth M. Rice, Rajesh Kumar, Sam Oh, Jose Rodriguez-Santana, Esteban G. Burchard, Max A. Seibold

Abstract
Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, an emerging virus that utilizes host proteins ACE2 and TMPRSS2 as entry factors. Understanding the factors affecting the pattern and levels of expression of these genes is important for deeper understanding of SARS-CoV-2 tropism and pathogenesis. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci for both ACE2 and TMPRSS2, that vary in frequency across world populations. We find TMPRSS2 is part of a mucus secretory network, highly upregulated by type 2 (T2) inflammation through the action of interleukin-13, and that the interferon response to respiratory viruses highly upregulates ACE2 expression. IL-13 and virus infection mediated effects on ACE2 expression were also observed at the protein level in the airway epithelium. Finally, we define airway responses to common coronavirus infections in children, finding that these infections generate host responses similar to other viral species, including upregulation of IL6 and ACE2. Our results reveal possible mechanisms influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.

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08/10/2020 Reviews
Type I IFN-dependent antibody response at the basis of sex dimorphism ...

Type I IFN-dependent antibody response at the basis of sex dimorphism in the outcome of COVID-19

ELSEVIER

Authors
Lucia Gabriele, Alessandra Fragale, Giulia Romagnoli, Stefania Parlato, Caterina Lapenta, Stefano Maria Santini, Keiko Ozato, Imerio Capone

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, induces severe pneumonia mainly in elderly males. Epidemiological data clearly indicate sex-based differences in disease outcomes, with men accounting for about 70% of deaths, despite similar susceptibility to infection. It is well known that females are endowed with higher capacity to produce antibodies, which correlates with viral clearance and disease resolution in the context of SARS-Cov-2 infection. Many X-linked immune genes escape X inactivation showing biallelic expression in female immune cells, particularly in plasmacytoid dendritic cells (pDCs). PDCs are more active in females and endowed with high capability to induce IFN-α-mediated B cell activation and differentiation into antibody-producing plasma cells throughout epigenetic mechanisms linked to trained immunity. Thus, we hypothesize that following SARS-CoV-2 infection, epigenetic modifications of X-linked genes involved in pDC-mediated type I IFN (IFN-I) signaling occurs more effectively in females, for inducing neutralizing antibody response as an immune correlate driving sex-biased disease outcome.

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08/10/2020 Letter
Reduced SARS-CoV-2 entry factors and enhanced innate immune gene expre...

Reduced SARS-CoV-2 entry factors and enhanced innate immune gene expression in the nasal epithelium of pregnant rats

AJOG (AMERICAN JOURNAL OBSTRETICS GYNECOLOGY)

Authors
Arvind Palanisamy, Tusar Giri

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08/10/2020 Articles
Persistence of serum and saliva antibody responses to SARS-CoV-2 spike...

Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients

SCIENCE

Authors
Baweleta Isho, Kento T. Abe, Michelle Zuo, Alainna J. Jamal, Bhavisha Rathod, Jenny H. Wang, Zhijie Li, Gary Chao, Olga L. Rojas, Yeo Myong Bang, Annie Pu, Natasha Christie-Holmes, Christian Gervais, Derek Ceccarelli, Payman Samavarchi-Tehrani, Furkan Guvenc, Patrick Budylowski, Angel Li, Aimee Paterson, Yue Feng Yun, Lina M. Marin, Lauren Caldwell, Jeffrey L. Wrana, Karen Colwill, Frank Sicheri, Samira Mubareka, Scott D. Gray-Owen, Steven J. Drews, Walter L. Siqueira, Miriam Barrios- Rodiles, Mario Ostrowski, James M. Rini, Yves Durocher, Allison J. McGeer, Jennifer L. Gommerman, Anne-Claude Gingras

Abstract
While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor-binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3–115 days post-symptom onset (PSO), compared to negative controls. Anti-SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16–30 days PSO. Longitudinal analysis revealed that anti-SARS-CoV-2 IgA and IgM antibodies rapidly decayed, while IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in the majority of COVID-19 patients for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

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07/10/2020 Articles
Extrafollicular B cell responses correlate with neutralizing antibodie...

Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19

NATURE

Authors
Matthew C. Woodruff, Richard P. Ramonell, Doan C. Nguyen, Kevin S. Cashman, Ankur Singh Saini, Natalie S. Haddad, Ariel M. Ley, Shuya Kyu, J. Christina Howell, Tugba Ozturk, Saeyun Lee, Naveenchandra Suryadevara, James Brett Case, Regina Bugrovsky, Weirong Chen, Jacob Estrada, Andrea Morrison-Porter, Andrew Derrico, Fabliha A. Anam, Monika Sharma, Henry M. Wu, Sang N. Le, Scott A. Jenks, Christopher M. Tipton, Bashar Staitieh, John L. Daiss, Eliver Ghosn, Michael S. Diamond, Robert H. Carnahan, James E. Crowe Jr., William T. Hu, F. Eun-Hyung Lee, Ignacio Sanz

Abstract
A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.

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01/10/2020 Letter
Waning of SARS-CoV-2 RBD antibodies in longitudinal convalescent plasm...

Waning of SARS-CoV-2 RBD antibodies in longitudinal convalescent plasma samples within four months after symptom onset

BLOOD (AMERICAN SOCIETY OF HEMATOLOGY)

Authors
Josée Perreault, Tony Tremblay, Marie-Josée Fournier, Mathieu Drouin, Guillaume Beaudoin-Bussières, Jérémie Prévost, Antoine Lewin, Philippe Bégin, Andrés Finzi, Renée Bazin

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30/09/2020 Articles
Severe COVID-19 is associated with elevated serum IgA and antiphosphol...

Severe COVID-19 is associated with elevated serum IgA and antiphospholipid IgA- antibodies

OXFORD ACADEMY

Authors
Omar Hasan Ali, David Bomze, Lorenz Risch, Silvio D Brugger, Matthias Paprotny, Myriam Weber, Sarah Thiel, Lukas Kern, Werner C Albrich, Philipp Kohler, Christian R Kahlert, Pietro Vernazza, Philipp K Buehler, Reto A Schuepbach, Alejandro Gomez-Mejia, Alexandra M Popa, Andreas Bergthaler, Josef M Penninger, Lukas Flatz

Abstract
Background
Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there is little data on possible IgA-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and if IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome (APS), our approach focused on antiphospholipid antibodies (aPL).

Methods
In this retrospective cohort study clinical data and aPL from 64 patients with COVID-19 were compared from three independent tertiary hospitals (one in Liechtenstein, two in Switzerland). Samples were collected from April 9 th to May 1 st, 2020.

Results
Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID) (41%), a discovery cohort with severe illness (sdCOVID) (22%) and a confirmation cohort with severe illness (scCOVID) (38%). Total IgA, IgG and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P=0.01; scCOVID, p-value<0.001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anti-Cardiolipin IgA (sdCOVID and scCOVID, p-value<0.001), anti-Cardiolipin IgM (sdCOVID, P=0.003; scCOVID, P<0.001), and anti-Beta2 Glycoprotein-1 IgA (sdCOVID and scCOVID, P<0.001). Systemic lupus erythematosus was excluded from all patients as a potential confounder.

Conclusions
Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA-response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity.

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30/09/2020 Articles
SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T...

SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition

NATURE

Authors
Annika Nelde, Tatjana Bilich, Jonas S. Heitmann, Yacine Maringer, Helmut R. Salih, Malte Roerden, Maren Lübke, Jens Bauer, Jonas Rieth, Marcel Wacker, Andreas Peter, Sebastian Hörber, Bjoern Traenkle, Philipp D. Kaiser, Ulrich Rothbauer, Matthias Becker, Daniel Junker, Gérard Krause, Monika Strengert, Nicole Schneiderhan-Marra, Markus F. Templin, Thomas O. Joos, Daniel J. Kowalewski, Vlatka Stos-Zweifel, Michael Fehr, Armin Rabsteyn, Valbona Mirakaj, Julia Karbach, Elke Jäger, Michael Graf, Lena-Christin Gruber, David Rachfalski, Beate Preuß, Ilona Hagelstein, Melanie Märklin, Tamam Bakchoul, Cécile Gouttefangeas, Oliver Kohlbacher, Reinhild Klein, Stefan Stevanović, Hans-Georg Rammensee, Juliane S. Walz

Abstract
T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.

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25/09/2020 Articles
Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of pa...

Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study

THE LANCET

Authors
Shuchi Anand, Maria Montez-Rath, Jialin Han, Julie Bozeman, Russell Kerschmann, Paul Beyer, Julie Parsonnet, Glenn M Chertow

Read More »

24/09/2020 Articles
Ultrapotent human antibodies protect against SARS-CoV-2 challenge via ...

Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

SCIENCE

Authors
M. Alejandra Tortorici, Martina Beltramello, Florian A. Lempp, Dora Pinto, Ha V. Dang, Laura E. Rosen, Matthew McCallum, John Bowen, Andrea Minola, Stefano Jaconi, Fabrizia Zatta, Anna De Marco, Barbara Guarino, Siro Bianchi3, Elvin J. Lauron, Heather Tucker, Jiayi Zhou, Alessia Peter, Colin Havenar- Daughton, Jason A. Wojcechowskyj, James Brett Case, Rita E. Chen, Hannah Kaiser, Martin Montiel-Ruiz, Marcel Meury, Nadine Czudnochowski, Roberto Spreafico, Josh Dillen, Cindy Ng, Nicole Sprugasci, Katja Culap, Fabio Benigni, Rana Abdelnabi, Shi-Yan Caroline Foo, Michael A. Schmid, Elisabetta Cameroni, Agostino Riva, Arianna Gabrieli, Massimo Galli, Matteo S. Pizzuto, Johan Neyts, Michael S. Diamond, Herbert W. Virgin, Gyorgy Snell, Davide Corti, Katja Fink, David Veesler

Abstract
Efficient therapeutic options are needed to control the spread of SARS-CoV-2 that has caused more than 922,000 fatalities as of September 13th, 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block ACE2 attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Cocktails including S2M11, S2E12 or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.

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24/09/2020 Articles
Hidden immune weakness found in 14% of gravely ill COVID-19 patients

SCIENCE

Authors
Meredith Wadman

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23/09/2020 Comment
The complexities of SARS-CoV-2 serology

THE LANCET

Authors
Catherine F Houlihan, Rupert Beale

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23/09/2020 Articles
SARS-CoV-2 antibody prevalence in Brazil: results from two successive ...

SARS-CoV-2 antibody prevalence in Brazil: results from two successive nationwide serological household surveys

THE LANCET

Authors
Pedro C Hallal, Fernando P Hartwig, Bernardo L Horta, Mariângela F Silveira, Claudio J Struchiner, Luís P Vidaletti, Nelson A Neumann, Lucia C Pellanda, Odir A Dellagostin, Marcelo N Burattini, Gabriel D Victora, Ana M B Menezes, Fernando C Barros, Aluísio J D Barros, Cesar G Victora

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23/09/2020 Articles
Performance characteristics of five immunoassays for SARS-CoV-2: a hea...

Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison

THE LANCET

Authors
The National SARS-CoV-2 Serology Assay Evaluation Group

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23/09/2020 Correspondence
Loss of Anti–SARS-CoV-2 Antibodies in Mild Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Edwin Bölke, Christiane Matuschek, Johannes C. Fischer

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23/09/2020 Case Report
Asymptomatic reinfection in two healthcare workers from India with ge...

Asymptomatic reinfection in two healthcare workers from India with genetically distinct SARS-CoV-2

OXFORD ACADEMY

Authors
Vivek Gupta, Rahul C Bhoyar, Abhinav Jain, Saurabh Srivastava, Rashmi Upadhayay, Mohamed Imran, Bani Jolly, Mohit Kumar Divakar, Disha Sharma, Paras Sehgal, Gyan Ranjan, Rakesh Gupta, Vinod Scaria, Sridhar Sivasubbu

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22/09/2020 Articles
Patients with Covid-19 exhibit different immunological profiles accord...

Patients with Covid-19 exhibit different immunological profiles according to their clinical presentation

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Authors
M. Vassallo, S. Manni, P. Pini, E. Blanchouin, M. Ticchioni, B. Seitz-Polski, A. Puchois, A. Sindt, L. Lotte, P. Fauque, J. Durant

Abstract
Objectives: A novel beta coronavirus has been identified as responsible for the
2019 coronavirus infection (Covid-19). Clinical presentations range from
asymptomatic cases to acute respiratory distress syndrome with fatal outcome.
Such a broad spectrum of disease expression calls for an investigation of
immune response characteristics.
Methods: We identified subjects admitted for Covid-19 in whom a large panel
of immunological markers were measured, including B- and T- and NKlymphocyte phenotypes, T-lymphocyte subpopulation cells and plasma
cytokines. Patients were divided according to symptom severity during
hospitalisation, in those with uncomplicated and complicated infection.
Differences between groups were analyzed.
Results: Seventeen patients were included (mean age: 83 years; 9 women; mean
delay of symptoms onset: 4 days). Six had uncomplicated infection, while 11
developed complicated forms during the hospitalization. CD10+ B lymphocyte
levels were inversely correlated with clinical severity (5.8% vs 2.0%, p = 0.04)
and CD10+ levels above 3% were independently associated with uncomplicated
forms [Odds Ratio 0.04 (CI 0.002-0.795, p = 0.034)].
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TNF-alpha, IL-1, Il-6 and Il-8 measurements upon admission differed between
patients who died and those who survived (p < 0.01 for all comparisons).
Conclusions: In a population of elderly patients recently infected with Covid19, CD10+ B cell levels were inversely correlated with clinical severity.
Cytokine values upon admission were highly predictive of fatal outcome during
hospitalisation. These findings could explain differences in the clinical
presentation and allow rapid identification of patients at risk for complications

Read More »

17/09/2020 Articles
A systematic review of antibody mediated immunity to coronaviruses: ki...

A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity

NATURE

Authors
Angkana T. Huang, Bernardo Garcia-Carreras, Matt D. T. Hitchings, Bingyi Yang, Leah C. Katzelnick, Susan M. Rattigan, Brooke A. Borgert, Carlos A. Moreno, Benjamin D. Solomon, Luke Trimmer-Smith, Veronique Etienne, Isabel Rodriguez-Barraquer, Justin Lessler, Henrik Salje, Donald S. Burke, Amy Wesolowski, Derek A. T. Cummings

Abstract
Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.

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17/09/2020 Letter
Change in Antibodies to SARS-CoV-2 Over 60 Days Among Health Care Pers...

Change in Antibodies to SARS-CoV-2 Over 60 Days Among Health Care Personnel in Nashville, Tennessee

JAMA

Authors
Manish M. Patel, Natalie J. Thornburg, William B. Stubblefield, H. Keipp Talbot, Melissa M. Coughlin, Leora R. Feldstein, Wesley H. Self

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15/09/2020 Articles
Clinical characteristics of family-clustered onset of coronavirus dise...

Clinical characteristics of family-clustered onset of coronavirus disease 2019 in Jilin Province, China

TAYLOR & FRANCIS ONLINE

Authors
Na Du , Yanfang Jiang , Qing Zhang , Lihe Che , Xiaohua Li , Lixin Lou , Wanguo Bao, Shucheng Hua

ABSTRACT
Eight members of a big family with laboratory-confirmed COVID-19 pneumonia were admitted to First Hospital of Jilin University, Changchun, China, from 28 January to 5 February 2020. The clinical records, laboratory results, and chest computed tomography (CT) scans were retrospectively reviewed. Throat swab samples were positive for severe acute respiratory syndrome coronavirus 2, confirmed by the Center for Disease Control and Prevention of Changchun. All eight patients had fever of different degrees; and 6, 3, and 2 had cough; diarrhea; and sore throat. With disease progression, the percentage of lymphocytes in older patients increased, CT images worsened, and the ratio of lymphocytes increased when images revealed inflammation absorption. Although the CT images showed ground-glass opacities in the youngest patient, his lymphocyte count did not decrease with mild clinical symptoms, and the images showed that inflammation was quickly absorbed. Only the oldest patient developed critical illness. The C reaction protein (CRP) levels of Patient 5 increased significantly, and the rate of decline was the slowest, while his condition was the most severe. The clinical manifestations of COVID-19 in this family cluster varied with contact, age, and underlying disease. Lymphocyte count and quality of chest CT images appeared inversely associated with disease severity. CRP changes may be an indicator of disease severity and prognosis.

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15/09/2020 Correspondence
Temporal antibody responses to SARS-CoV-2 in patients of coronavirus d...

Temporal antibody responses to SARS-CoV-2 in patients of coronavirus disease 2019

CELL DISCOVERY

Authors
Min Huang, Qing-Bin Lu, Han Zhao, Yulan Zhang, Zhiwei Sui, Liqun Fang, Di Liu, Xiulian Sun, Ke Peng, Wei Liu, Wuxiang Guan

Read More »

14/09/2020 Articles
Case-Control Study of Use of Personal Protective Measures and Risk for...

Case-Control Study of Use of Personal Protective Measures and Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Thailand

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
Pawinee Doung-ngern, Repeepong Suphanchaimat, Apinya Panjangampatthana, Chawisar Janekrongtham, Duangrat Ruampoom, Nawaporn Daochaeng, Napatchakorn Eungkanit, Nichakul Pisitpayat, Nuengruethai Srisong, Oiythip Yasopa, Patchanee Plernprom, Pitiphon Promduangsi, Panita Kumphon, Paphanij Suangtho, Peeriya Watakulsin, Sarinya Chaiya, Somkid Kripattanapong, Thanawadee Chantian, Emily Bloss, Chawetsan Namwat, Direk Limmathurotsakul

Abstract
We evaluated effectiveness of personal protective measures against severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Our case-control study included 211 cases of coronavirus disease (COVID-19) and 839 controls in Thailand. Cases were defined as asymptomatic contacts of COVID-19 patients who later tested positive for SARS-CoV-2; controls were asymptomatic contacts who never tested positive. Wearing masks all the time during contact was independently associated with lower risk for SARS-CoV-2 infection compared with not wearing masks; wearing a mask sometimes during contact did not lower infection risk. We found the type of mask worn was not independently associated with infection and that contacts who always wore masks were more likely to practice social distancing. Maintaining >1 m distance from a person with COVID-19, having close contact for <15 minutes, and frequent handwashing were independently associated with lower risk for infection. Our findings support consistent wearing of masks, handwashing, and social distancing to protect against COVID-19.

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14/09/2020 Brief Report
Kinetics of SARS-CoV-2 Antibody Avidity Maturation and Association wit...

Kinetics of SARS-CoV-2 Antibody Avidity Maturation and Association with Disease Severity

OXFORD ACADEMY

Authors
Yiqi Ruben Luo, Indrani Chakraborty, Cassandra Yun, Alan H B Wu, Kara L Lynch

Abstract
The kinetics of IgG avidity maturation during SARS-CoV-2 infection was studied. The IgG avidity assay used a novel label-free immunoassay technology. It was found that there was a strong correlation between IgG avidity and days since symptom onset, and peak readings were significantly higher in severe than mild disease cases.

Read More »

14/09/2020 Short Communication
Seasonal coronavirus protective immunity is short-lasting

NATURE

Authors
Arthur W. D. Edridge, Joanna Kaczorowska, Alexis C. R. Hoste, Margreet Bakker, Michelle Klein, Katherine Loens, Maarten F. Jebbink, Amy Matser, Cormac M. Kinsella, Paloma Rueda, Margareta Ieven, Herman Goossens, Maria Prins, Patricia Sastre, Martin Deijs, Lia van der Hoek

Abstract
A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection.

Read More »

11/09/2020 Viewpoint
COVID-19 and the Path to Immunity

JAMA

Authors
David S. Stephens, M. Juliana McElrath

Read More »

10/09/2020 Research
Trained Innate Immunity, Epigenetics, and Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Alberto Mantovani., Mihai G. Netea

Read More »

09/09/2020 Articles
Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies

NATURE

Authors
Wen Shi Lee, Adam K. Wheatley, Stephen J. Kent & Brandon J. DeKosky

ABSTRACT
Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclinical and clinical development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clinical safety risks related to ADE, resulting in failed vaccine trials. Here, we describe key ADE mechanisms and discuss mitigation strategies for SARS-CoV-2 vaccines and therapies in development. We also outline recently published data to evaluate the risks and opportunities for antibody-based protection against SARS-CoV-2.

Read More »

07/09/2020 News
T cells in COVID-19 — united in diversity

NATURE

Authors
Leo Swadling, Mala K. Maini

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07/09/2020 Articles
Covid-19 Hyperinflammation and Post-Covid-19 Illness May Be Rooted in ...

Covid-19 Hyperinflammation and Post-Covid-19 Illness May Be Rooted in Mast Cell Activation Syndrome

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Authors
Lawrence B. Afrin, Leonard B. Weinstock, Gerhard J. Molderings

Abstract
Objectives: One-fifth of Covid-19 patients suffer a severely symptomatic, hyperinflammatory
course, but specific causes remain unclear. Mast cells (MCs) are activated by SARS-CoV-2.
Though only recently recognized, MC activation syndrome (MCAS), usually due to acquired
MC clonality, is a chronic multisystem disorder with inflammatory and allergic themes and
estimated prevalence of 17%. We describe a novel conjecture explaining how MCAS might
cause propensity for severe acute Covid-19 infection and chronic post-Covid-19 illnesses.
Methods: Observations of Covid-19 illness in patients with/without MCAS, set against our
extensive clinical experience with MCAS.
Journal Pre-proof
4
Results: The prevalence of MCAS is concordant with the prevalence of severe cases within the
Covid-19-infected population. Much of Covid-19’s hyperinflammation is concordant with
manners of inflammation which MC activation can drive. Drugs with activity against MCs or
their mediators have been preliminarily observed helpful in Covid-19 patients. None of our
treated MCAS patients who have endured Covid-19 infection have suffered severe courses of the
infection, let alone mortality.
Conclusions: Hyperinflammatory cytokine storms in many severely symptomatic Covid-19
patients may be rooted in aberrant response to SARS-CoV-2 by the dysfunctional MCs of MCAS
rather than normal response by normal MCs. If provable, our conjecture has significant
therapeutic and prognostic implications.

Read More »

04/09/2020 Brief Report
Phenotypical and functional alteration of unconventional T cells in se...

Phenotypical and functional alteration of unconventional T cells in severe COVID-19 patients

JEM (JOURNAL OF EXPERIMENTAL MEDICINE)

Authors
Youenn Jouan, Antoine Guillon, Loïc Gonzalez, Yonatan Perez, Chloé Boisseau, Stephan Ehrmann, Marion Ferreira, Thomas Daix, Robin Jeannet, Bruno François, Pierre-François Dequin, Mustapha Si-Tahar, Thomas Baranek, Christophe Paget

Read More »

04/09/2020 Articles
High Potency of a Bivalent Human VH Domain in SARS-CoV-2 Animal Models

CELL

Authors
Wei Li, Alexandra Schäfer Swarali S. Kulkarni Xianglei Liu David R. Martinez Chuan Chen Zehua Sun Sarah R. Leist Aleksandra Drelich Liyong Zhang Marcin L. Ura Alison Berezuk Sagar Chittori Karoline Leopold Dhiraj Mannar Shanti S. Srivastava Xing Zhu Eric C. Peterson Chien-Te Tseng John W. Mellors Darryl Falzarano Sriram Subramaniam Ralph S. Baric Dimiter S. Dimitrov

Read More »

04/09/2020 Articles
Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in...

Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

NATURE

Authors
Yanchun Peng, Alexander J. Mentzer, Guihai Liu, Xuan Yao, Zixi Yin, Danning Dong, Wanwisa Dejnirattisai, Timothy Rostron, Piyada Supasa, Chang Liu, César López-Camacho, Jose Slon-Campos, Yuguang Zhao, David I. Stuart, Guido C. Paesen, Jonathan M. Grimes, Alfred A. Antson, Oliver W. Bayfield, Dorothy E. D. P. Hawkins, De-Sheng Ker, Beibei Wang, Lance Turtle, Krishanthi Subramaniam, Paul Thomson, Ping Zhang, Christina Dold, Jeremy Ratcliff, Peter Simmonds, Thushan de Silva, Paul Sopp, Dannielle Wellington, Ushani Rajapaksa, Yi-Ling Chen, Mariolina Salio, Giorgio Napolitani, Wayne Paes, Persephone Borrow, Benedikt M. Kessler, Jeremy W. Fry, Nikolai F. Schwabe, Malcolm G. Semple, J. Kenneth Baillie, Shona C. Moore, Peter J. M. Openshaw, M. Azim Ansari, Susanna Dunachie, Eleanor Barnes, John Frater, Georgina Kerr, Philip Goulder, Teresa Lockett, Robert Levin, Yonghong Zhang, Ronghua Jing, Ling-Pei Ho, Oxford Immunology Network Covid-19 Response T cell Consortium, ISARIC4C Investigators, Richard J. Cornall, Christopher P. Conlon, Paul Klenerman, Gavin R. Screaton, Juthathip Mongkolsapaya, Andrew McMichael, Julian C. Knight, Graham Ogg, Tao Dong

ABSTRACT
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide–MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

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04/09/2020 Articles
Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in...

Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

NATURE

Authors
Yanchun Peng, Alexander J. Mentzer, Guihai Liu, Xuan Yao, Zixi Yin, Danning Dong, Wanwisa Dejnirattisai, Timothy Rostron, Piyada Supasa, Chang Liu, César López-Camacho, Jose Slon-Campos, Yuguang Zhao, David I. Stuart, Guido C. Paesen, Jonathan M. Grimes, Alfred A. Antson, Oliver W. Bayfield, Dorothy E. D. P. Hawkins, De-Sheng Ker, Beibei Wang, Lance Turtle, Krishanthi Subramaniam, Paul Thomson, Ping Zhang, Christina Dold, Jeremy Ratcliff, Peter Simmonds, Thushan de Silva, Paul Sopp, Dannielle Wellington, Ushani Rajapaksa, Yi-Ling Chen, Mariolina Salio, Giorgio Napolitani, Wayne Paes, Persephone Borrow, Benedikt M. Kessler, Jeremy W. Fry, Nikolai F. Schwabe, Malcolm G. Semple, J. Kenneth Baillie, Shona C. Moore, Peter J. M. Openshaw, M. Azim Ansari, Susanna Dunachie, Eleanor Barnes, John Frater, Georgina Kerr, Philip Goulder, Teresa Lockett, Robert Levin, Yonghong Zhang, Ronghua Jing, Ling-Pei Ho, Oxford Immunology Network Covid-19 Response T cell Consortium, ISARIC4C Investigators, Richard J. Cornall, Christopher P. Conlon, Paul Klenerman, Gavin R. Screaton, Juthathip Mongkolsapaya, Andrew McMichael, Julian C. Knight, Graham Ogg, Tao Dong

ABSTRACT
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide–MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

31/08/2020 Letter
Immune characteristics of severe and critical COVID-19 patients

NATURE

Authors
Li Yang, Jianjun Gou, Jianbo Gao, Lan Huang, Zhiqiang Zhu, Shaofei Ji, Hongchun Liu, Lihua Xing, Mengying Yao, Yi Zhang

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28/08/2020 Articles
Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, At...

Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, Atlanta, Georgia, USA, 2020

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
William T. Hu, J. Christina Howell, Tugba Ozturk, Karima Benameur, Leda C. Bassit, Richard Ramonell, Kevin S. Cashman, Shama Pirmohammed, John D. Roback, Vincent C. Marconi, Irene Yang, Valerie V. Mac, Daniel Smith, Ignacio Sanz, Whitney Wharton, F. Eun-Hyung Lee, Raymond F. Schinazi

Abstract
Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.

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21/08/2020 Articles
A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike...

A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction

NATURE

Authors
Monir Ejemel, Qi Li, Shurong Hou, Zachary A. Schiller, Julia A. Tree, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Karen R. Buttigieg, Michael J. Elmore, Kerry Godwin, Naomi Coombes, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Brianna J. Close, Da-Yuan Chen, Hasahn L. Conway, Mohsan Saeed, Chandrashekar Ganesa, Miles W. Carroll, Lisa A. Cavacini, Mark S. Klempner, Celia A. Schiffer, Yang Wang


ABSTRACT
COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.

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19/08/2020 Articles
SARS-CoV-2-specific T cells exhibit phenotypic features of robust help...

SARS-CoV-2-specific T cells exhibit phenotypic features of robust helper function, lack of terminal differentiation, and high proliferative potential

CELL

Authors
JasonNeidleman, XiaoyuLuo, JulieFrouard, GuoruiXie, GurjotGill, Ellen S.Stein, MatthewMcGregor, TongcuiMa, Ashley F.George, AstridKosters, Warner C.Greene, JoshuaVasquez, EliverGhosn, SulggiLee, Nadia R.Roan

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17/08/2020 News
COVID-19 poses a riddle for the immune system

NATURE

Authors
STANLEY PERLMAN

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14/08/2020 Articles
Robust T cell immunity in convalescent individuals with asymptomatic o...

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

CELL

Authors
Julian Braun, Lucie Loyal, Marco Frentsch, Daniel Wendisch, Philipp Georg, Florian Kurth, Stefan Hippenstiel, Manuela Dingeldey, Beate Kruse, Florent Fauchere, Emre Baysal, Maike Mangold, Larissa Henze, Roland Lauster, Marcus A. Mall, Kirsten Beyer, Jobst Röhmel, Sebastian Voigt, Jürgen Schmitz, Stefan Miltenyi, Ilja Demuth, Marcel A. Müller, Andreas Hocke, Martin Witzenrath, Norbert Suttorp, Florian Kern, Ulf Reimer, Holger Wenschuh, Christian Drosten, Victor M. Corman, Claudia Giesecke-Thiel, Leif Erik Sander, Andreas Thiel

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03/08/2020 New Result
Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conser...

Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity

BIORXIV

Authors
Hejun Liu, Nicholas C. Wu, Meng Yuan, ..., Rogier W. Sanders, Andrew B. Ward, Ian A. Wilson

ABSTRACT
Most antibodies isolated from COVID-19 patients are specific to SARS-CoV-2. COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here we determined a crystal structure of COVA1-16 Fab with the SARS-CoV-2 RBD, and a negative-stain EM reconstruction with the spike glycoprotein trimer, to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long CDR H3, and competes with ACE2 binding due to steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with structural and functional rationale for the epitope conservation, provide a blueprint for development of more universal SARS-like coronavirus vaccines and therapies.

Competing Interest Statement
Amsterdam UMC previously filed a patent application on the SARS-CoV-2 antibody COVA1-16 described here.

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29/07/2020 Articles
SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-...

SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

NATURE

Authors
Julian Braun, Lucie Loyal, Marco Frentsch, Daniel Wendisch, Philipp Georg, Florian Kurth, Stefan Hippenstiel, Manuela Dingeldey, Beate Kruse, Florent Fauchere, Emre Baysal, Maike Mangold, Larissa Henze, Roland Lauster, Marcus A. Mall, Kirsten Beyer, Jobst Röhmel, Sebastian Voigt, Jürgen Schmitz, Stefan Miltenyi, Ilja Demuth, Marcel A. Müller, Andreas Hocke, Martin Witzenrath, Norbert Suttorp, Florian Kern, Ulf Reimer, Holger Wenschuh, Christian Drosten, Victor M. Corman, Claudia Giesecke-Thiel, Leif Erik Sander, Andreas Thiel


ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms determining such variable outcomes remain unresolved. Here, we investigated SARS-CoV-2 spike glycoprotein (S)-reactive CD4+ T cells in peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors (HD). We detected SARS-CoV-2 S-reactive CD4+ T cells in 83% of patients with COVID-19 but also in 35% of HD. S-reactive CD4+ T cells in HD reacted primarily to C-terminal S epitopes, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared to N-terminal epitopes. S-reactive T cell lines generated from SARS-CoV-2-naive HD responded similarly to C-terminal S of human endemic coronaviruses 229E and OC43 and SARS-CoV-2, demonstrating the presence of S-cross-reactive T cells, probably generated during past encounters with endemic coronaviruses. The role of pre-existing SARS-CoV-2 cross-reactive T cells for clinical outcomes remains to be determined in larger cohorts. However, the presence of S-cross-reactive T cells in a sizable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming COVID-19 vaccine trials.

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28/07/2020 Articles
Immune T Cells May Offer Lasting Protection Against COVID-19

NIH

Authors
Francis Collins



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27/07/2020 Articles
Longitudinal analyses reveal immunological misfiring in severe COVID-1...

Longitudinal analyses reveal immunological misfiring in severe COVID-19

NATURE

Authors
Carolina Lucas, Patrick Wong, Jon Klein, Tiago B. R. Castro, Julio Silva, Maria Sundaram, Mallory K. Ellingson, Tianyang Mao, Ji Eun Oh, Benjamin Israelow, Takehiro Takahashi, Maria Tokuyama, Peiwen Lu, Arvind Venkataraman, Annsea Park, Subhasis Mohanty, Haowei Wang, Anne L. Wyllie, Chantal B. F. Vogels, Rebecca Earnest, Sarah Lapidus, Isabel M. Ott, Adam J. Moore, M. Catherine Muenker, John B. Fournier, Melissa Campbell, Camila D. Odio, Arnau Casanovas-Massana, Yale IMPACT Team, Roy Herbst, Albert C. Shaw, Ruslan Medzhitov, Wade L. Schulz, Nathan D. Grubaugh, Charles Dela Cruz, Shelli Farhadian, Albert I. Ko, Saad B. Omer, Akiko Iwasaki



ABSTRACT
Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1–4. Yet, longitudinal immunological correlates of disease outcome remain unclear. Here, we serially analysed immune responses in 113 COVID-19 patients with moderate (non-ICU) and severe (ICU) disease. Immune profiling revealed an overall increase in innate cell lineages with a concomitant reduction in T cell number. We identify an association between early, elevated cytokines and worse disease outcomes. Following an early increase in cytokines, COVID-19 patients with moderate disease displayed a progressive reduction in type-1 (antiviral) and type-3 (antifungal) responses. In contrast, patients with severe disease maintained these elevated responses throughout the course of disease. Moreover, severe disease was accompanied by an increase in multiple type 2 (anti-helminths) effectors including, IL-5, IL-13, IgE and eosinophils. Unsupervised clustering analysis identified 4 immune signatures, representing (A) growth factors, (B) type-2/3 cytokines, (C) mixed type-1/2/3 cytokines, and (D) chemokines that correlated with three distinct disease trajectories of patients. The immune profile of patients who recovered with moderate disease was enriched in tissue reparative growth factor signature (A), while the profile for those with worsened disease trajectory had elevated levels of all four signatures. Thus, we identified development of a maladapted immune response profile associated with severe COVID-19 outcome and early immune signatures that correlate with divergent disease trajectories.

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25/07/2020 Articles
COVID-19: immunopathogenesis and Immunotherapeutics

NATURE

Authors
Li Yang, Shasha Liu, Jinyan Liu, Zhixin Zhang, Xiaochun Wan, Bo Huang, Youhai Chen, Yi Zhang



ABSTRACT
The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seeing a rapid increase in infected patients worldwide. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 not only activates antiviral immune responses, but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19, leading to lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities. These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease. Moreover, rational management of the immune responses to SARS-CoV-2, which includes enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. In this review, we discuss the immunopathology of COVID-19, its potential mechanisms, and clinical implications to aid the development of new therapeutic strategies against COVID-19.

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22/07/2020 Report
Rapid Scaling Up of Covid-19 Diagnostic Testing in the United States —...

Rapid Scaling Up of Covid-19 Diagnostic Testing in the United States — The NIH RADx Initiative

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Bruce J. Tromberg, Tara A. Schwetz,, Eliseo J. Pérez‐Stable, Richard J. Hodes, Richard P. Woychik, Rick A. Bright, Rachael L. Fleurence, Francis S. Collins



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21/07/2020 New Result
S Protein-Reactive IgG and Memory B Cell Production after Human SARS-C...

S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit

BIORXIV

Authors
Phuong Nguyen-Contant, A. Karim Embong, Preshetha Kanagaiah, Francisco A. Chaves, Hongmei Yang, Angela R. Branche, David J. Topham, Mark Y. Sangstera

ABSTRACT
The high susceptibility of humans to SARS-CoV-2 infection, the cause of COVID-19, reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and PBMCs from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 in convalescent subjects were higher than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.

IMPORTANCE Recent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key questions are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and post-infection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study also suggests that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.

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21/07/2020 New Result
S protein-reactive IgG and memory B cell production after human SARS-C...

S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit

Authors
Phuong Nguyen-Contant, A. Karim Embong, Preshetha Kanagaiah, Francisco A. Chaves, Hongmei Yang, Angela R. Branche, David J. Topham, Y. Sangster



ABSTRACT
The high susceptibility of humans to SARS-CoV-2 infection, the cause of COVID-19, reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and PBMCs from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 in convalescent subjects were higher than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.

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17/07/2020 Report
Structural basis for translational shutdown and immune evasion by the ...

Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

SCIENCE

Authors
Matthias Thoms, Robert Buschauer, Michael Ameismeier, Lennart Koepke, Timo Denk, Maximilian Hirschenberger, Hanna Kratzat, Manuel Hayn, Timur Mackens-Kiani, Jingdong Cheng, Jan H. Straub, Christina M. Stürzel, Thomas Fröhlich, Otto Berninghausen, Thomas Becker, Frank Kirchhoff, Konstantin M. J. Sparrer, Roland Beckmann



ABSTRACT
SARS-CoV-2 is the causative agent of the current COVID-19 pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1) which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40S ribosomal subunit, resulting in shutdown of mRNA translation both in vitro and in cells. Structural analysis by cryo-electron microscopy (cryo-EM) of in vitro reconstituted Nsp1-40S and various native Nsp1-40S and -80S complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks RIG-I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.

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17/07/2020 Articles
Routine childhood immunisation during the COVID-19 pandemic in Africa:...

Routine childhood immunisation during the COVID-19 pandemic in Africa: a benefit–risk analysis of health benefits versus excess risk of SARS-CoV-2 infection

THE LANCET

Authors
Kaja Abbas, Simon R Procter, Kevin van Zandvoort, Andrew Clark, Sebastian Funk, Tewodaj Mengistu, Dan Hogan, Emily Dansereau, Mark Jit, Stefan Flasche,



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16/07/2020 Research
Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-...

Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2

EUROSURVEILLANCE

Authors
Zhiqiang Zheng, Vanessa Marthe Monteil , Sebastian Maurer-Stroh , Chow Wenn Yew , Carol Leong , Nur Khairiah Mohd-Ismail, Suganya Cheyyatraivendran Arularasu, Vincent Tak Kwong Chow, Raymond Tzer Pin Lin, Ali Mirazimi , Wanjin Hong, Yee-Joo Tan



ABSTRACT
Background A novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002–2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.
Aim The cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.
Methods The SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.
Results An immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.
Conclusion The cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.

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15/07/2020 Articles
SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and...

SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls

NATURE

Authors
Nina Le Bert, Anthony T. Tan, Kamini Kunasegaran, Christine Y. L. Tham, Morteza Hafezi, Adeline Chia, Melissa Hui Yen Chng, Meiyin Lin, Nicole Tan, Martin Linster, Wan Ni Chia, Mark I-Cheng Chen, Lin-Fa Wang, Eng Eong Ooi, Shirin Kalimuddin, Paul Anantharajal Tambyah, Jenny Guek-Hong Low, Yee-Joo Tan, Antonio Bertoletti



ABSTRACT
Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections1. Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved amongst animal betacoranaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.

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13/07/2020 Communication
Estimating the efficacy of symptom-based screening for COVID-19

NATURE

Authors
Alison Callahan, Ethan Steinberg, Jason A. Fries, Saurabh Gombar, Birju Patel, Conor K. Corbin, Nigam H. Shah



ABSTRACT
There is substantial interest in using presenting symptoms to prioritize testing for COVID-19 and establish symptom-based surveillance. However, little is currently known about the specificity of COVID-19 symptoms. To assess the feasibility of symptom-based screening for COVID-19, we used data from tests for common respiratory viruses and SARS-CoV-2 in our health system to measure the ability to correctly classify virus test results based on presenting symptoms. Based on these results, symptom-based screening may not be an effective strategy to identify individuals who should be tested for SARS-CoV-2 infection or to obtain a leading indicator of new COVID-19 cases.

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12/07/2020 Reviews
SARS‐CoV‐2: An immunogenetics call to arms

WILEY ONLINE LIBRARY

Authors
Brendan Clark, Kay Poulton



ABSTRACT
Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS‐Cov‐2 pandemic, this review considers existing immunogenetic knowledge of virus‐immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.

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09/07/2020 Communication
International external quality assessment for SARS- CoV-2 molecular de...

International external quality assessment for SARS- CoV-2 molecular detection and survey on clinical laboratory preparedness during the COVID-19 pandemic, April/May 2020

EUROSURVEILLANCE

Authors
Veerle Matheeussen , Victor M Corman , Oliver Donoso Mantke , Elaine McCulloch , Christine Lammens , Herman Goossens , Daniela Niemeyer , Paul S Wallace , Paul Klapper , Hubert GM Niesters , Christian Drosten , Margareta Ieven



ABSTRACT
Laboratory preparedness with quality-assured diagnostic assays is essential for controlling the current coronavirus disease (COVID-19) outbreak. We conducted an external quality assessment study with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples to support clinical laboratories with a proficiency testing option for molecular assays. To analyse SARS-CoV-2 testing performance, we used an online questionnaire developed for the European Union project RECOVER to assess molecular testing capacities in clinical diagnostic laboratories.

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07/07/2020 Articles
Serological differentiation between COVID-19 and SARS infections

TAYLOR & FRANCIS ONLINE

Authors
Wan Ni Chia , Chee Wah Tan , Randy Foo , Adrian Eng Zheng Kang , Yilong Peng , Velraj Sivalingam , Charles Tiu , Xin Mei Ong , Feng Zhu , Barnaby E. Young , Mark I.-C. Chen , Yee-Joo Tan , David C. Lye , Danielle E. Anderson, Lin-Fa Wang

ABSTRACT
In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, multiple diagnostic tests are required for acute disease diagnosis, contact tracing, monitoring asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed. Unlike PCR tests which are highly specific, cross-reactivity is a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. SARS-CoV is genetically related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus in the genus Betacoronavirus of family Coronaviridae. We developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. There is significant cross-reactivity when N protein of either virus is used. The S1 or RBD regions from the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. We found that SARS survivors all have significant levels of antibodies remaining in their blood 17 years after infection. Anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.

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06/07/2020 Articles
An evaluation of COVID-19 serological assays informs future diagnostic...

An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment

NATURE

Authors
Corine H. GeurtsvanKessel, Nisreen M. A. Okba, Zsofia Igloi, Susanne Bogers, Carmen W. E. Embregts, Brigitta M. Laksono, Lonneke Leijten, Casper Rokx, Bart Rijnders, Janette Rahamat-Langendoen, Johannes P. C. van den Akker, Jeroen J. A. van Kampen, Annemiek A. van der Eijk, Rob S. van Binnendijk, Bart Haagmans, Marion Koopmans



ABSTRACT
The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.

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03/07/2020 Letter
Retrospective Screening for SARS-CoV-2 RNA in California, USA, Late 20...

Retrospective Screening for SARS-CoV-2 RNA in California, USA, Late 2019

CDC

Authors
Catherine A. Hogan, Natasha Garamani, Malaya K. Sahoo, ChunHong Huang, James Zehnder, Benjamin A. Pinsky



ABSTRACT
To investigate the possibility of earlier cases of severe acute respiratory syndrome coronavirus 2 infection than previously recognized, we retrospectively tested pooled samples from 1,700 persons with respiratory signs/symptoms seen at Stanford Health Care, Palo Alto, California, USA, during the last 2 months of 2019. We found no evidence of earlier infection.

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03/07/2020 Articles
High neutralizing antibody titer in intensive care unit patients with ...

High neutralizing antibody titer in intensive care unit patients with COVID-19

TAYLOR & FRANCIS ONLINE

Authors
Li Liu , Kelvin Kai-Wang To , Kwok-Hung Chan , Yik-Chun Wong , Runhong Zhou , Ka-Yi Kwan , Carol Ho-Yan Fong , Lin-Lei Chen , Charlotte Yee-Ki Choi , Lu Lu , Owen Tak-Yin Tsang , Wai-Shing Leung , Wing-Kin To , Ivan Fan-Ngai Hung , Kwok-Yung Yuen, Zhiwei Chen



ABSTRACT
Coronavirus disease 2019 (COVID-19) has a wide spectrum of disease severity from mild upper respiratory symptoms to respiratory failure. The role of neutralizing antibody (NAb) response in disease progression remains elusive. This study determined the seroprevalence of 733 non-COVID-19 individuals from April 2018 to February 2020 in the Hong Kong Special Administrative Region and compared the neutralizing antibody (NAb) responses of eight COVID-19 patients admitted to the intensive care unit (ICU) with those of 42 patients not admitted to the ICU. We found that NAb against SARS-CoV-2 was not detectable in any of the anonymous serum specimens from the 733 non-COVID-19 individuals. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 [95% confidence interval (CI) 1468-36099]) vs 671 [95% CI, 368-1223]). Furthermore, NAb titer increased significantly at earlier infection stages among ICU patients than among non-ICU patients. The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). Multivariate analysis showed that oxygen requirement and fever during admission were the only clinical factors independently associated with higher NAb titers. Our data suggested that SARS-CoV-2 was unlikely to have silently spread before the COVID-19 emergence in Hong Kong. ICU patients had an accelerated and augmented NAb response compared to non-ICU patients, which was associated with disease severity. Further studies are required to understand the relationship between high NAb response and disease severity.

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03/07/2020 Highlights
Finding Camel-ot: A Holy Grail against pandemic SARS-CoV-2?

SCIENCE

Authors
Deborah Soong, Rachel Leeman, Asha Pillai



ABSTRACT
Engineered camelid antibody multimers can potently block SARS-CoV-2 viral entry.

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03/07/2020 Letter
Immunosenescence exacerbates the COVID-19

ELSEVIER

Authors
Claudio Napoli, Isabella Tritto, Gelsomina Mansueto, Enrico Coscioni, Giuseppe Ambrosio


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02/07/2020 HEALTHCARE WORKERS
Overview of Testing for SARS-CoV-2

CDC

Authors
National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases


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01/07/2020 Manuscript
Immune modulation in COVID-19: Strategic considerations for personaliz...

Immune modulation in COVID-19: Strategic considerations for personalized therapeutic intervention

OXFORD ACADEMY

Authors
Mark W. Hall, Ila Joshi, Luis Leal ,Eng Eong Ooi



ABSTRACT
We are learning that the host response to SARS-CoV-2 infection is complex and highly dynamic. Effective initial host defense in the lung is associated with mild symptoms and disease resolution. Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction. The immune response in these patients is highly variable and can include moderate to severe systemic inflammation and/or marked systemic immune suppression. There is unlikely to be a “one size fits all” approach to immunomodulation in patients with COVID-19. We believe that a personalized, immunophenotype-driven approach to immunomodulation that may include anti-cytokine therapy in carefully selected patients and immunostimulatory therapies in others is the shortest path to success in the study and treatment of patients with critical illness due to COVID-19.

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30/06/2020 Letter
Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, C...

Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents

CDC

Authors
Arnaud G. L’Huillier, Giulia Torriani, Fiona Pigny, Laurent Kaiser, Isabella Eckerle



ABSTRACT
Children do not seem to drive transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We isolated culture-competent virus in vitro from 12 (52%) of 23 SARS-CoV-2–infected children; the youngest was 7 days old. Our findings show that symptomatic neonates, children, and teenagers shed infectious SARS-CoV-2, suggesting that transmission from them is plausible.

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30/06/2020 Analysis
Interpretazione dei test diagnostici per SARS-Cov-2

ARS TOSCANA

Authors
C. Silvestri, C. Stasi


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27/06/2020 Letter
Immunomodulation for the management of corona virus disease (COVID-19)

ELSEVIER

Authors
Dobri Kiprov, Michael J.Conboy, Irina M.Conboy


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27/06/2020 Articles
Test sensitivity is secondary to frequency and turnaround time for COV...

Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance

MEDRXIV

Authors
Daniel B. Larremore, Bryan Wilder, Evan Lester, Soraya Shehata, James M. Burke, James A. Hay, Milind Tambe, Michael J. Mina, Roy Parker



ABSTRACT
The COVID-19 pandemic has created a public health crisis. Because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, the re-opening of societies and the control of virus spread will be facilitated by robust surveillance, for which virus testing will often be central. After infection, individuals undergo a period of incubation during which viral titers are usually too low to detect, followed by an exponential growth of virus, leading to a peak viral load and infectiousness, and ending with declining viral levels and clearance. Given the pattern of viral load kinetics, we model surveillance effectiveness considering test sensitivities, frequency, and sample-to-answer reporting time. These results demonstrate that effective surveillance, including time to first detection and outbreak control, depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity. We therefore conclude that surveillance should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.


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25/06/2020 Articles
Antibody tests for identification of current and past infection with S...

Antibody tests for identification of current and past infection with SARS‐CoV‐2

COCHRANE LIBRARY

Authors
Jonathan J Deeks, Jacqueline Dinnes,Yemisi Takwoingi, Clare Davenport, René Spijker, Sian Taylor-Phillips, Ada Adriano, Sophie Beese, Janine Dretzke, Lavinia Ferrante di Ruffano, Isobel M Harris, Malcolm J Price, Sabine Dittrich, Devy Emperador, Lotty Hooft, Mariska MG Leeflang, Ann Van den Bruel



ABSTRACT
Background The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus and resulting COVID‐19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify current infection, rule out infection, identify people in need of care escalation, or to test for past infection and immune response. Serology tests to detect the presence of antibodies to SARS‐CoV‐2 aim to identify previous SARS‐CoV‐2 infection, and may help to confirm the presence of current infection.
Objectives To assess the diagnostic accuracy of antibody tests to determine if a person presenting in the community or in primary or secondary care has SARS‐CoV‐2 infection, or has previously had SARS‐CoV‐2 infection, and the accuracy of antibody tests for use in seroprevalence surveys.
Search methods We undertook electronic searches in the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID‐19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 27 April 2020.
Selection criteria We included test accuracy studies of any design that evaluated antibody tests (including enzyme‐linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in people suspected of current or previous SARS‐CoV‐2 infection, or where tests were used to screen for infection. We also included studies of people either known to have, or not to have SARS‐CoV‐2 infection. We included all reference standards to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction tests (RT‐PCR) and clinical diagnostic criteria). Data collection and analysis We assessed possible bias and applicability of the studies using the QUADAS‐2 tool. We extracted 2x2 contingency table data and present sensitivity and specificity for each antibody (or combination of antibodies) using paired forest plots. We pooled data using random‐effects logistic regression where appropriate, stratifying by time since post‐symptom onset. We tabulated available data by test manufacturer. We have presented uncertainty in estimates of sensitivity and specificity using 95% confidence intervals (CIs).
Main results We included 57 publications reporting on a total of 54 study cohorts with 15,976 samples, of which 8526 were from cases of SARS‐CoV‐2 infection. Studies were conducted in Asia (n = 38), Europe (n = 15), and the USA and China (n = 1). We identified data from 25 commercial tests and numerous in‐house assays, a small fraction of the 279 antibody assays listed by the Foundation for Innovative Diagnostics. More than half (n = 28) of the studies included were only available as preprints.
We had concerns about risk of bias and applicability. Common issues were use of multi‐group designs (n = 29), inclusion of only COVID‐19 cases (n = 19), lack of blinding of the index test (n = 49) and reference standard (n = 29), differential verification (n = 22), and the lack of clarity about participant numbers, characteristics and study exclusions (n = 47). Most studies (n = 44) only included people hospitalised due to suspected or confirmed COVID‐19 infection. There were no studies exclusively in asymptomatic participants. Two‐thirds of the studies (n = 33) defined COVID‐19 cases based on RT‐PCR results alone, ignoring the potential for false‐negative RT‐PCR results. We observed evidence of selective publication of study findings through omission of the identity of tests (n = 5).
We observed substantial heterogeneity in sensitivities of IgA, IgM and IgG antibodies, or combinations thereof, for results aggregated across different time periods post‐symptom onset (range 0% to 100% for all target antibodies). We thus based the main results of the review on the 38 studies that stratified results by time since symptom onset. The numbers of individuals contributing data within each study each week are small and are usually not based on tracking the same groups of patients over time.
Pooled results for IgG, IgM, IgA, total antibodies and IgG/IgM all showed low sensitivity during the first week since onset of symptoms (all less than 30.1%), rising in the second week and reaching their highest values in the third week. The combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. Estimates of accuracy beyond three weeks are based on smaller sample sizes and fewer studies. For 21 to 35 days, pooled sensitivities for IgG/IgM were 96.0% (95% CI 90.6 to 98.3). There are insufficient studies to estimate sensitivity of tests beyond 35 days post‐symptom onset. Summary specificities (provided in 35 studies) exceeded 98% for all target antibodies with confidence intervals no more than 2 percentage points wide. False‐positive results were more common where COVID‐19 had been suspected and ruled out, but numbers were small and the difference was within the range expected by chance.
Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post‐symptom onset. At a prevalence of 20%, a likely value in surveys in high‐risk settings, 17 (11 to 26) would be missed per 1000 people tested and 10 (5 to 22) would be falsely positive. At a lower prevalence of 5%, a likely value in national surveys, 4 (3 to 7) would be missed per 1000 tested, and 12 (6 to 27) would be falsely positive.
Analyses showed small differences in sensitivity between assay type, but methodological concerns and sparse data prevent comparisons between test brands.
Authors' conclusions The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID‐19, but they may still have a role complementing other testing in individuals presenting later, when RT‐PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS‐CoV‐2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days post‐symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalised patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID‐19 disease.
The design, execution and reporting of studies of the accuracy of COVID‐19 tests requires considerable improvement. Studies must report data on sensitivity disaggregated by time since onset of symptoms. COVID‐19‐positive cases who are RT‐PCR‐negative should be included as well as those confirmed RT‐PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are available in the public domain to prevent selective reporting. This is a fast‐moving field and we plan ongoing updates of this living systematic review.

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24/06/2020 Features
Covid-19 antibody tests: a briefing

THE BMJ

Authors
Chris Baraniuk


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24/06/2020 Letter
Age-related decline of de novo T cell responsiveness as a cause of COV...

Age-related decline of de novo T cell responsiveness as a cause of COVID-19 severity

SPRINGER LINK

Authors
Francesco Nicoli, Maria Teresa Solis-Soto, Deepak Paudel, Peggy Marconi, Riccardo Gavioli, Victor Appay, Antonella Caputo


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23/06/2020 Research
ADL-dependency, D-Dimers, LDH and absence of anticoagulation are indep...

ADL-dependency, D-Dimers, LDH and absence of anticoagulation are independently associated with one-month mortality in older inpatients with Covid-19

AGING

Authors
Guilhem Bousquet, Géraldine Falgarone, David Deutsch, Sophie Derolez, Marilucy Lopez-Sublet, François-Xavier Goudot, Khadaoudj Amari, Yurdagul Uzunhan, Olivier Bouchaud, Frédéric Pamoukdjian


ABSTRACT
Background: To assess factors associated with one-month mortality among older inpatients with Covid-19.
Results: The mean age was 78 ± 7.8 years, 55.5% were men, CT scan lung damage was observed in 76% of the patients (mild 23%, moderate 38%, extensive 22%, and severe 7%). The mortality rate was 26%. Dependency/Activities of Daily Living (ADL) score ≤ 5/6, D-Dimers, LDH, and no anticoagulation by reference for curative were independently associated with one-month mortality. A score derived from the multivariate model showed good calibration and very good discrimination (Harrell’s C index [95%CI] = 0.83 [0.79-0.87]).
Conclusion: ADL-dependency, high serum levels of D-Dimers and LDH and the absence of anticoagulation were independently associated with one-month mortality among older inpatients with Covid-19.
Methods: 108 consecutive older inpatients aged 65 and over with Covid-19 confirmed by RT-PCR and/or typical CT chest scan were prospectively included in a French single-centre cohort study from March to April 2020. A systematic geriatric assessment was performed. Covariates were lymphocyte count, serum levels of albumin, C-Reactive Protein, D-Dimers and Lactate Dehydrogenase (LDH), anticoagulation level, and exposure to the hydroxychloroquine and azithromycin combined therapy. Cox uni- and multivariate proportional-hazard regressions were performed to identify predictors of one-month mortality.

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18/06/2020 Rapid Communication
Multicentre comparison of quantitative PCR-based assays to detect SARS...

Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020

EUROSURVEILLANCE

Authors
Maximilian Muenchhoff, Helga Mairhofer, Hans Nitschko, Natascha Grzimek-Koschewa, Dieter Hoffmann, Annemarie Berger, Holger Rabenau, Marek Widera, Nikolaus Ackermann, Regina Konrad, Sabine Zange, Alexander Graf, Stefan Krebs, Helmut Blum, Andreas Sing, Bernhard Liebl, Roman Wölfel, Sandra Ciesek, Christian Drosten, Ulrike Protzer, Stephan Boehm, Oliver T Keppler



ABSTRACT
Containment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.

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18/06/2020 Articles
Convergent antibody responses to SARS-CoV-2 in convalescent individual...

Convergent antibody responses to SARS-CoV-2 in convalescent individuals

NATURE

Authors
Davide F. Robbiani, Christian Gaebler, Michel C. Nussenzweig



ABSTRACT
During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

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16/06/2020 Reviews
Immunology of COVID-19: Current State of the Science

SCIENCE DIRECT

Authors
Nicolas Vabret, Graham J. Britton, Conor Gruber, Samarth Hegde, Joel Kim, Maria Kuksin, Rachel Levantovsky, Louise Malle, Alvaro Moreira, Matthew D. Park, Luisanna Pia, Emma Risson, Miriam Saffern, Be ́rengere Salome, Myvizhi Esai Selvan, Matthew P. Spindler, Jessica Tan, Verena van der Heide, Jill K. Gregory, Konstantina Alexandropoulos, Nina Bhardwaj, Brian D. Brown, Benjamin Greenbaum, Zeynep H., Dirk Homann, Amir Horowitz, Alice O. Kamphorst, Maria A. Curotto de Lafaille, Saurabh Mehandru, Miriam Merad, Robert M. Samstein



ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this Review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.

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15/06/2020 Articles
Potent neutralizing antibodies from COVID-19 patients define multiple ...

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

NATURE

Authors
Philip J. M. Brouwer, Tom G. Caniels, Karlijn van der Straten, Jonne L. Snitselaar, Yoann Aldon, Sandhya Bangaru, Jonathan L. Torres, Nisreen M. A. Okba, Mathieu Claireaux, Gius Kerster, Arthur E. H. Bentlage, Marlies M. van Haaren, Denise Guerra, Judith A. Burger, Edith E. Schermer, Kirsten D. Verheul, Niels van der Velde, Alex van der Kooi, Jelle van Schooten, Mariëlle J. van Breemen, Tom P. L. Bijl,Kwinten Sliepen, Aafke Aartse, Ronald Derking, Ilja Bontjer, Neeltje A. Kootstra, W. Joost Wiersinga, Gestur Vidarsson, Bart L. Haagmans, Andrew B. Ward,Godelieve J. de Bree, Rogier W. Sanders, J. van Gils



ABSTRACT
The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3 and VH1-24 gene usage. A subset of the antibodies were able to potently inhibit authentic SARS-CoV-2 infection as low as 0.007 μg/mL. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.


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15/06/2020 Report
Broad neutralization of SARS-related viruses by human monoclonal antib...

Broad neutralization of SARS-related viruses by human monoclonal antibodies

SCIENCE

Authors
Anna Z. Wec, Daniel Wrapp, Andrew S. Herbert, Daniel P. Maurer, Denise Haslwanter, Mrunal Sakharkar, Rohit K. Jangra, M. Eugenia Dieterle, Asparouh Lilov, Deli Huang, Longping V. Tse, Nicole V. Johnson, Ching-Lin Hsieh, Nianshuang Wang, Juergen H. Nett, Elizabeth Champney, Irina Burnina, Michael Brown, Shu Lin, Melanie Sinclair, Carl Johnson, Sarat Pudi, Robert Bortz III, Ariel S. Wirchnianski, Ethan Laudermilch, Catalina Florez, J. Maximilian Fels, Cecilia M. O’Brien, Barney S. Graham,David Nemazee, Dennis R. Burton, Ralph S. Baric, James E. Voss, Kartik Chandran, John M. Dye, Jason S. McLellan, Laura M. Walker



ABSTRACT
Broadly protective vaccines against known and pre-emergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.


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15/06/2020 Report
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutationa...

Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies

NATURE

Authors
Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, Christos A. Kyratsous



ABSTRACT
Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. We investigate the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared following in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein. Importantly, escape mutants were not generated following treatment with a non-competing antibody cocktail.

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11/06/2020 Features
Too slow and fundamentally flawed: why test and trace is a weak and in...

Too slow and fundamentally flawed: why test and trace is a weak and inequitable defence against covid-19

THE BMJ

Authors
RICHARD VIZE


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11/06/2020 Articles
Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerlan...

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study

THE LANCET

Authors
Silvia Stringhini, Ania Wisniak, Giovanni Piumatti, Andrew S Azman, Stephen A Lauer, Hélène Baysson, David De Ridder, Dusan Petrovic, Stephanie Schrempft, Kailing Marcus, Sabine Yerly, Isabelle Arm Vernez, Prof Olivia Keiser, Prof Samia Hurst, Prof Klara M Posfay-Barbe, Prof Didier Trono, Prof Didier Pittet, Laurent Gétaz, Prof François Chappuis, Prof Isabella Eckerle, Prof Nicolas Vuilleumier, Benjamin Meyer, Prof Antoine Flahault, Prof Laurent Kaiser, Prof Idris Guessous,


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10/06/2020 Viewpoint
The Importance of Proper Death Certification During the COVID-19 Pande...

The Importance of Proper Death Certification During the COVID-19 Pandemic

JAMA

Authors
James R. Gill, Maura E. DeJoseph


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08/06/2020 Articles
Expansion of myeloid-derived suppressor cells in patients with severe ...

Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19)

NATURE

Authors
Chiara Agrati, Alessandra Sacchi, Veronica Bordoni, Eleonora Cimini, Stefania Notari, Germana Grassi, Rita Casetti, Eleonora Tartaglia, Eleonora Lalle, Alessandra D’Abramo, Concetta Castilletti, Luisa Marchioni, Yufang Shi, Andrea Mariano, Jin-Wen Song, Ji-Yuan Zhang, Fu-Sheng Wang, Chao Zhang, Gian Maria Fimia, Maria R. Capobianchi, Mauro Piacentini, Andrea Antinori, Emanuele Nicastri, Markus Maeurer, Alimuddin Zumla, Giuseppe Ippolito



ABSTRACT
SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-β, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-β and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.


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08/06/2020 Letter
A single-cell atlas of the peripheral immune response in patients with...

A single-cell atlas of the peripheral immune response in patients with severe COVID-19

NATURE

Authors
Aaron J. Wilk, Arjun Rustagi, Nancy Q. Zhao, Jonasel Roque, Giovanny J. Martínez-Colón, Julia L. McKechnie, Geoffrey T. Ivison, Thanmayi Ranganath, Rosemary Vergara, Taylor Hollis, Laura J. Simpson, Philip Grant, Aruna Subramanian, Angela J. Rogers, Catherine A. Blish



ABSTRACT
There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines3,4 that may be produced by a subset of inflammatory monocytes5,6, lymphopenia7,8 and T cell exhaustion9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.

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05/06/2020 PERSPECTIVE
Waiting for Certainty on Covid-19 Antibody Tests — At What Cost?

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Milton C. Weinstein, Kenneth A. Freedberg, Emily P. Hyle, A. David Paltiel


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05/06/2020 PERSPECTIVE
False Negative Tests for SARS-CoV-2 Infection — Challenges and Implica...

False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Steven Woloshin, Neeraj Patel, Aaron S. Kesselheim



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04/06/2020 Letter
Viral RNA Load in Mildly Symptomatic and Asymptomatic Children with CO...

Viral RNA Load in Mildly Symptomatic and Asymptomatic Children with COVID-19, Seoul

CENTRE FOR DISEASE AND CONTROL PREVENTION

Authors
Mi Seon Han, Moon-Woo Seong, Namhee Kim, Sue Shin, Sung Im Cho, Hyunwoong Park, Taek Soo Kim, Sung Sup Park, Eun Hwa Choi


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04/06/2020 Letter
Viral RNA Load in Mildly Symptomatic and Asymptomatic Children with CO...

Viral RNA Load in Mildly Symptomatic and Asymptomatic Children with COVID-19, Seoul

CENTRE FOR DISEASE AND CONTROL PREVENTION

Authors
Mi Seon Han, Moon-Woo Seong, Namhee Kim, Sue Shin, Sung Im Cho, Hyunwoong Park, Taek Soo Kim, Sung Sup Park, Eun Hwa Choi


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01/06/2020 Articles
Evaluation of novel antigen-based rapid detection test for the diagnos...

Evaluation of novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples

ELSEVIER

Authors
Lorena Porte, Paulette Legarraga, Valeska Vollrath, Ximena Aguilera, José M.Munita, Rafael Araos,Gabriel Pizarro, Pablo Vial ,Mirentxu Iruretagoyena, Sabine Dittrichfg, Thomas Weitzelad



ABSTRACT
Objectives In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We evaluated a novel rapid antigen detection test (RDT) for SARS-CoV-2 in respiratory samples.
Methods The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected Covid-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real time (RT)-PCR.
Results A total of 127 samples were included; 82 were RT-PCR positive. Median patients’ age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (CI95% 86.5–97.4) and 100% (CI95% 92.1–100), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads.
Conclusions The evaluated RDT showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.

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01/06/2020 Articles
Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutra...

Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients

NATURE

Authors
Chek Meng Poh, Guillaume Carissimo, Bei Wang, Siti Naqiah Amrun, Cheryl Yi-Pin Lee, Rhonda Sin-Ling Chee, Siew-Wai Fong, Nicholas Kim-Wah Yeo, Wen-Hsin Lee, Anthony Torres-Ruesta, Yee-Sin Leo, Mark I-Cheng Chen, Seow-Yen Tan, Louis Yi Ann Chai, Shirin Kalimuddin, Shirley Seah Gek Kheng, Siew-Yee Thien, Barnaby Edward Young, David C. Lye, Brendon John Hanson, Cheng-I Wang, Laurent Renia & Lisa F. P. Ng

ABSTRACT

Given the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the coronavirus spike glycoprotein will provide crucial advances towards the development of sensitive diagnostic tools and potential vaccine candidate targets. In this study, using pools of overlapping linear B-cell peptides, we report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralisation capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus.

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01/06/2020 Articles
Delayed specific IgM antibody responses observed among COVID-19 patien...

Delayed specific IgM antibody responses observed among COVID-19 patients with severe progression

TAYLOR & FRANCIS ONLINE

Authors
Liang Shen, Chunhua Wang, Jianzhong Zhao, Xiaoyong Tang, Ying Shen, Mingqing Lu, Zhe Ding, Canping Huang, Ji Zhang, Shichao Li, Jiaming Lan, Gary Wong, Yufang Zhu

ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide since it was confirmed as the causative agent of COVID-19. Molecular diagnosis of the disease is typically performed via nucleic acid-based detection of the virus from swabs, sputum or bronchoalveolar lavage fluid (BALF). However, the positive rate from the commonly used specimens (swabs or sputum) was less than 75%. Immunological assays for SARS-CoV-2 are needed to accurately diagnose COVID-19. Sera were collected from patients or healthy people in a local hospital in Xiangyang, Hubei Province, China. The SARS-CoV-2 specific IgM antibodies were then detected using a SARS-CoV-2 IgM colloidal gold immunochromatographic assay (GICA). Results were analysed in combination with sera collection date and clinical information. The GICA was found to be positive with the detected 82.2% (37/45) of RT-qPCR confirmed COVID-19 cases, as well as 32.0% (8/25) of clinically confirmed, RT-qPCR negative patients (4–14 days after symptom onset). Investigation of IgM-negative, RT-qPCR-positive COVID-19 patients showed that half of them developed severe disease. The GICA was found to be a useful test to complement existing PCR-based assays for confirmation of COVID-19, and a delayed specific IgM antibody response was observed among COVID-19 patients with severe progression.

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30/05/2020 Correspondence
Increased sFLT1/PlGF ratio in COVID-19: a novel link to Angiotensin II...

Increased sFLT1/PlGF ratio in COVID-19: a novel link to Angiotensin II-mediated endothelial dysfunction

WILEY ONLINE LIBRARY

Authors
Valentina Giardini, Andrea Carrer, Marco Casati, Ernesto Contro, Patrizia Vergani, Carlo Gambacorti‐Passerini


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28/05/2020 Correspondence
Implication of SARS-CoV-2 evolution in the sensitivity of RT-qPCR diag...

Implication of SARS-CoV-2 evolution in the sensitivity of RT-qPCR diagnostic assays

The Lancet

Authors
Nuno Sampaio Osório, Margarida Correia-Neves

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28/05/2020 Opinion Article
Coronavirus Disease (Covid-19): What Are We Learning in a Country With...

Coronavirus Disease (Covid-19): What Are We Learning in a Country With High Mortality Rate?

FRONTIERS IN IMMUNOLOGY

Authors
Luciano Mutti, Francesca Pentimalli, Giovanni Baglio, Patrizia Maiorano, Rita Emilena Saladino, Pierpaolo Correale, Antonio Giordano

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26/05/2020 Articles
Human neutralizing antibodies elicited by SARS-CoV-2 infection

NATURE

Authors
Bin Ju, Qi Zhang, Jiwan Ge, Ruoke Wang, Jing Sun, Xiangyang Ge, Jiazhen Yu, Sisi Shan, Bing Zhou, Shuo Song, Xian Tang, Jinfang Yu, Jun Lan, Jing Yuan, Haiyan Wang, Juanjuan Zhao, Shuye Zhang, Youchun Wang, Xuanling Shi, Lei Liu, Jincun Zhao, Xinquan Wang, Zheng Zhang & Linqi Zhang

ABSTRACT
The emerging coronavirus SARS-CoV-2 pandemic presents a global health emergency in urgent need of interventions1–3. SARS-CoV-2 entry into the target cells depends on binding between the receptor-binding domain (RBD) of the viral Spike protein and the ACE2 cell receptor2,4–6. Here, we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells of eight SARS-CoV-2 infected individuals. We identified antibodies with potent anti-SARS-CoV-2 neutralization activity that correlates with their competitive capacity with ACE2 for RBD binding. Surprisingly, neither the anti-SARS-CoV-2 antibodies nor the infected plasma cross-reacted with SARS-CoV or MERS-CoV RBDs, although substantial plasma cross-reactivity to their trimeric Spike proteins was found. Crystal structure analysis of RBD-bound antibody revealed steric hindrance that inhibits viral engagement with ACE2 and thereby blocks viral entry. These findings suggest that anti-RBD antibodies are viral species-specific inhibitors. The antibodies identified here may be candidates for the development of SARS-CoV-2 clinical interventions.

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26/05/2020 Articles
A human neutralizing antibody targets the receptor binding site of SAR...

A human neutralizing antibody targets the receptor binding site of SARS-CoV-2

NATURE

Authors
Rui Shi, Chao Shan, Xiaomin Duan, Zhihai Chen, Peipei Liu, Jinwen Song, Tao Song, Xiaoshan Bi, Chao Han, Lianao Wu, Ge Gao, Xue Hu, Yanan Zhang, Zhou Tong, Weijin Huang, William Jun Liu, Guizhen Wu, Bo Zhang, Lan Wang, Jianxun Qi, Hui Feng, Fu-sheng Wang, Qihui Wang, George Fu Gao, Zhiming Yuan & Jinghua Yan

ABSTRACT
An outbreak of the coronavirus disease 2019 (COVID-19)1–3, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4 spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. In this study, we report the isolation of 2 specific human monoclonal antibodies (MAbs) from a convalescent COVID-19 patient. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro against SARS-CoV-2. In addition, CB6 inhibited SARS-CoV-2 infection in rhesus monkeys at both prophylactic and treatment settings. Further structural studies revealed that CB6 recognizes an epitope that overlaps with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 receptor binding domain (RBD), thereby interfering with the virus/receptor interactions by both steric hindrance and direct interface-residue competition. Our results suggest CB6 deserves further clinical translation.

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22/05/2020 New Result
Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent ...

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

BIORXIV

Authors
Davide F. Robbiani, Christian Gaebler, Frauke Muecksch, Julio C. C. Lorenzi, Zijun Wang, Alice Cho, Marianna Agudelo, Christopher O. Barnes, Anna Gazumyan, Shlomo Finkin, Thomas Hagglof, Thiago Y. Oliveira, Charlotte Viant, Arlene Hurley, Hans-Heinrich Hoffmann, Katrina G. Millard, Rhonda G. Kost, Melissa Cipolla, Kristie Gordon, Filippo Bianchini, Spencer T. Chen, Victor Ramos, Roshni Patel, Juan Dizon, Irina Shimeliovich, Pilar Mendoza, Harald Hartweger, Lilian Nogueira, Maggi Pack, Jill Horowitz, Fabian Schmidt, Yiska Weisblum, Eleftherios Michailidis, Alison W. Ashbrook, Eric Waltari, John E. Pak, Kathryn E. Huey-Tubman, Nicholas Koranda, Pauline R. Hoffman, Anthony P. West Jr., Charles M. Rice, Theodora Hatziioannou, Pamela J. Bjorkman, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig

ABSTRACT
During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

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21/05/2020 Original Article
Immunoinformatic analysis of the SARS-CoV-2 envelope protein as a stra...

Immunoinformatic analysis of the SARS-CoV-2 envelope protein as a strategy to assess cross-protection against COVID-19

ELSEVIER

Authors
Bruno Tilocca, Alessio Soggiu, Maurizio Sanguinetti, Gabriele Babini, Flavio De Maio, Domenico Britti, Alfonso Zecconi, Luigi Bonizzi, Andrea Urbani, Paola Roncada

ABSTRACT
Envelope protein of coronaviruses is a structural protein existing in both monomeric and homo-pentameric form. It has been related to a multitude of roles including virus infection, replication, dissemination and immune response stimulation. In the present study, we employed an immunoinformatic approach to investigate the major immunogenic domains of the SARS-CoV-2 envelope protein and map them among the homologue proteins of coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Also, when not available, we predicted the envelope protein structural folding and mapped SARS-CoV-2 epitopes. Envelope sequences alignment provides evidence of high sequence homology for some of the investigated virus specimens; while the structural mapping of epitopes resulted in the interesting maintenance of the structural folding and epitope sequence localization also in the envelope proteins scoring a lower alignment score. In line with the One-Health approach, our evidences provide a molecular structural rationale for a potential role of taxonomically related coronaviruses in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies.

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20/05/2020 Articles
Targets of T cell responses to SARS-CoV-2 coronavirus in humans with C...

Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

SCIENCE DIRECT

Authors
Alba Grifoni, Daniela Weiskopf, Sydney I. Ramirez, Jose Mateus, Jennifer M. Dan, Carolyn Rydyznski Moderbacher, Stephen A. Rawlings, Aaron Sutherland, Lakshmanane Premkumar, Ramesh S. Jadi, Daniel Marrama, Aravinda M. de Silva, April Frazier, Aaron Carlin, Jason A. Greenbaum, Bjoern Peters, Florian Krammer, Davey M. Smith, Shane Crotty, Alessandro Sette

Read More »

20/05/2020 Review
The immunology of COVID-19: is immune modulation an option for treatme...

The immunology of COVID-19: is immune modulation an option for treatment?

The Lancet

Authors
Jixin Zhong, Jungen Tang, Cong Ye, Lingli Dong

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18/05/2020 Articles
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV anti...

Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody Nature

NATURE

Authors
Dora Pinto, Young-Jun Park, Martina Beltramello, Alexandra C. Walls, M. Alejandra Tortorici, Siro Bianchi, Stefano Jaconi, Katja Culap, Fabrizia Zatta, Anna De Marco, Alessia Peter, Barbara Guarino, Roberto Spreafico, Elisabetta Cameroni, James Brett Case, Rita E. Chen, Colin Havenar-Daughton, Gyorgy Snell, Amalio Telenti, Herbert W. Virgin, Antonio Lanzavecchia, Michael S. Diamond, Katja Fink, David Veesler, Davide Corti

ABSTRACT

SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with SARS-CoV in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

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18/05/2020 News and View
CRISPR tool scales up to interrogate a huge line-up of viral suspects

NATURE

Authors
Gregory A. Storch

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18/05/2020 Correspondence
Detection of IgM and IgG antibodies against SARS-CoV-2 in patients wit...

Detection of IgM and IgG antibodies against SARS-CoV-2 in patients with autoimmune diseases

The Lancet

Authors
Jialin Teng, Jin Dai, Yutong Su, Zhuochao Zhou, Huihui Chi, Liyan Wan, Jianfen Meng, Zhihong Wang, Fan Wang, Yuning Ma, Qiongyi Hu, Xiaobing Cheng, Honglei Liu, Junna Ye, Hui Shi, Yue Sun, Chengde Yang, Xuefeng Wang

Read More »

15/05/2020 Articles
Key residues of the receptor binding motif in the spike protein of SAR...

Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact...

Cellular & Molecular Immunology

Authors
Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling, Bing Sun

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.

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15/05/2020 Comment
Who is most likely to be infected with SARS-CoV-2?

The Lancet

Authors
Rachel E Jordan, Peymane Adab

ABSTRACT

The rapid spread of the corona virus pandemic is an existential problem for many people in numerous countries. So far, there is no effective vaccine protection or proven therapy available against the SARS-CoV-2 virus. In this review, we describe the role of passive immunization in times of the corona virus. Passive immunization could be a bridging technology to improve the immune defense of critically ill patients until better approaches with effective medications are available.

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13/05/2020 Review
The role of passive immunization in the age of SARS-CoV-2: an update

BMW

Authors
Johannes C. Fischer, Kurt Zänker, Martijn van Griensven, Marion Schneider, Detlef Kindgen-Milles, Wolfram Trudo Knoefel, Artur Lichtenberg, Balint Tamaskovics, Freddy Joel Djiepmo-Njanang, Wilfried Budach, Stefanie Corradini, Ute Ganswindt, Dieter Häussinger, Torsten Feldt, Hubert Schelzig, Hans Bojar, Matthias Peiper, Edwin Bölke, Jan Haussmann, Christiane Matuschek

ABSTRACT

The rapid spread of the corona virus pandemic is an existential problem for many people in numerous countries. So far, there is no effective vaccine protection or proven therapy available against the SARS-CoV-2 virus. In this review, we describe the role of passive immunization in times of the corona virus. Passive immunization could be a bridging technology to improve the immune defense of critically ill patients until better approaches with effective medications are available.

Read More »

11/05/2020 Viewpoint
COVID-19 and Postinfection Immunity Limited Evidence, Many Remaining Q...

COVID-19 and Postinfection Immunity Limited Evidence, Many Remaining Questions

JAMA

Authors
Prannoy Paul

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08/05/2020 News
First CRISPR test for the coronavirus approved in the United States

NATURE

Authors
Giorgia Guglielmi

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07/05/2020 Letter
Cardiac Troponin-I may be a predictor of complications and mortality i...

Cardiac Troponin-I may be a predictor of complications and mortality in COVID-19 patients

ELSEVIER

Authors
Prannoy Paul

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07/05/2020 Viewpoint
Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 ...

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia

The Lancet

Authors
Dennis McGonagle, James S O&rsquo;Donnell, Kassem Sharif, Paul Emery, Charles Bridgewood

Read More »

07/05/2020 Editorial
Persistence of viral RNA in stool samples from patients recovering fro...

Persistence of viral RNA in stool samples from patients recovering from covid-19

THE BMJ

Authors
Roos E Barth, Marieke J A De Regt

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06/05/2020 Viewpoint
Interpreting Diagnostic Tests for SARS-CoV-2

JAMA

Authors
Nandini Sethuraman, Sundararaj Stanleyraj Jeremiah; Akihide Ryo

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06/05/2020 Comment
The immune system of children: the key to understanding SARS-CoV-2 sus...

The immune system of children: the key to understanding SARS-CoV-2 susceptibility?

The Lancet

Authors
Rita Carsetti, Concetta Quintarelli, Isabella Quinti, Eva Piano Mortari, Alimuddin Zumla, Giuseppe Ippolito, Franco Locatelli

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04/05/2020 Articles
Self-collection: An appropriate alternative during the SARS-CoV-2 pand...

Self-collection: An appropriate alternative during the SARS-CoV-2 pandemic

ELSEVIER

Authors
Michael C. Wehrhahna, Jennifer Robsonb, Suzanne Brownc, Evan Bursleb, Shane Byrneb, David Newd, Smathi Chongd, James P. Newcombea,Terri Siverstena, Narelle Hadlowd

ABSTRACT

Objectives To evaluate the reliability of self-collection for SARS-CoV-2 and other respiratory viruses because swab collections for SARS-CoV-2 put health workers at risk of infection and require use of personal protective equipment (PPE).

Methods In a prospective study, patients from two states in Australia attending dedicated COVID-19 collection clinics were offered the option to first self-collect (SC) nasal and throat swabs (SCNT) prior to health worker collect (HC) using throat and nasal swabs (Site 1) or throat and nasopharyngeal swabs (Site 2). Samples were analysed for SARS-CoV-2 as well as common respiratory viruses. Concordance of results between methods was assessed using Cohen's kappa (κ) and Cycle threshold (Ct) values were recorded for all positive results as a surrogate measure for viral load.

Results Of 236 patients sampled by HC and SC, 25 had SARS-CoV-2 (24 by HC and 25 by SC) and 63 had other respiratory viruses (56 by HC and 58 by SC). SC was highly concordant with HC (κ = 0.890) for all viruses including SARS-CoV-2 and more concordant than HC to positive results by any method (κ = 0.959 vs 0.933). Mean SARS-CoV-2 E-gene and N-gene, rhinovirus and parainfluenza Ct values did not differ between HC and SCNT.

Conclusions Self-collection of nasal and throat swabs offers a reliable alternative to health worker collection for the diagnosis of SARS-CoV-2 and other respiratory viruses and provides patients with easier access to testing, reduces exposure of the community and health workers to those being tested and reduces requirement for PPE.

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04/05/2020 Articles
A human monoclonal antibody blocking SARS-CoV-2 infection

NATURE COMMUNICATIONS<

Authors
Chunyan Wang, Wentao Li, Dubravka Drabek, Nisreen M. A. Okba, Rien van Haperen, Albert D. M. E. Osterhaus, Frank J. M. van Kuppeveld, Bart L. Haagmans, Frank Grosveld & Berend-Jan Bosch

ABSTRACT


The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.

Read More »

02/05/2020 Letter
Different longitudinal patterns of nucleic acid and serology testing r...

Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients

TAYLOR & FRANCIS ONLINE

Authors
Zhang Yongchen, Han Shen, Xinning Wang, Xudong Shi, Yang Li, Jiawei Yan, Yuxin Chen, Bing Gu

ABSTRACT
Effective strategy to mitigate the ongoing pandemic of 2019 novel coronavirus (COVID-19) require a comprehensive understanding of humoral responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the emerging virus causing COVID-19. The dynamic profile of viral replication and shedding along with viral antigen specific antibody responses among COVID-19 patients started to be reported but there is no consensus on their patterns. Here, we conducted a serial investigation on 21 individuals infected with SARS-CoV-2 in two medical centres from Jiangsu Province, including 11 non-severe COVID-19 patients, and 5 severe COVID-19 patients and 5 asymptomatic carriers based on nucleic acid test and clinical symptoms. The longitudinal swab samples and sera were collected from these people for viral RNA testing and antibody responses, respectively. Our data revealed different pattern of seroconversion among these groups. All 11 non-severe COVID-19 patients and 5 severe COVID-19 patients were seroconverted during hospitalization or follow-up period, suggesting that serological testing is a complementary assay to nucleic acid test for those symptomatic COVID-19 patients. Of note, immediate antibody responses were identified among severe cases, compared to non-severe cases. On the other hand, only one were seroconverted for asymptomatic carriers. The SARS-CoV-2 specific antibody responses were well-maintained during the observation period. Such information is of immediate relevance and would assist COVID-19 clinical diagnosis, prognosis and vaccine design.

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29/04/2020 News
Covid-19: Antibody test that claims to be 99% accurate is certified by...

Covid-19: Antibody test that claims to be 99% accurate is certified by EU

BMJ

Authors
Elisabeth Mahase

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29/04/2020 Brief Communication
Antibody responses to SARS-CoV-2 in patients with COVID-19

NATURE MEDICINE

Authors
Quan-Xin Long, Bai-Zhong Liu, Hai-Jun Deng, Gui-Cheng Wu, Kun Deng, Yao-Kai Chen, Pu Liao, Jing-Fu Qiu, Yong Lin, Xue-Fei Cai, De-Qiang Wang, Yuan Hu, Ji-Hua Ren, Ni Tang, Yin-Yin Xu, Li-Hua Yu, Zhan Mo, Fang Gong, Xiao-Li Zhang, Wen-Guang Tian, Li Hu, Xian-Xiang Zhang, Jiang-Lin Xiang, Hong-Xin Du, Hua-Wen Liu, Chun-Hui Lang, Xiao-He Luo, Shao-Bo Wu, Xiao-Ping Cui, Zheng Zhou, Man-Man Zhu, Jing Wang, Cheng-Jun Xue, Xiao-Feng Li, Li Wang, Zhi-Jie Li, Kun Wang, Chang-Chun Niu, Qing-Jun Yang, Xiao-Jun Tang, Yong Zhang, Xia-Mao Liu, Jin-Jing Li, De-Chun Zhang, Fan Zhang, Ping Liu, Jun Yuan, Qin Li, Jie-Li Hu, Juan Chen & Ai-Long Huang

ABSTRACT

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections.

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23/04/2020 Comment
Complement as a target in COVID-19?

NATURE

Authors
Antonio M. Risitano, Dimitrios C. Mastellos , Markus Huber-Lang, Despina Yancopoulou Cecilia Garlanda Fabio Ciceri and John D. Lambris

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22/04/2020 Medical Hypotheses
The powerful immune system against powerful COVID-19: A hypothesis

ELSEVIER

Authors
Farzad Taghizadeh-Hesarya, Hassan Akbaria

ABSTRACT

On March 11, 2020, the World Health Organization declared the coronavirus outbreak a pandemic. Since December 2019, the world has experienced an outbreak of coronavirus disease 2019 (COVID-19). Epidemiology, risk factors, and clinical characteristics of patients with COVID-19 have been reported but the factors affecting the immune system against COVID-19 have not been well described. In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19.

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22/04/2020 Letter
How to Perform Pediatric Lung Ultrasound Examinations in the Time of C...

How to Perform Pediatric Lung Ultrasound Examinations in the Time of COVID-19

WILEY

Authors
Cristina De RosE Riccardo Inchingolo Andrea Smargiassi Giuseppe Zampino Piero Valentini Danilo Buonsenso

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21/04/2020 Comment
The important role of serology for COVID-19 control

The Lancet

Authors
Amy K Winter, Sonia T Hegde

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17/04/2020 Articles
Distinct early IgA profile may determine severity of COVID-19 symptoms...

Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series

MEDRXIV

Authors
Christine Dahlke, Jasmin Heidepriem, Robin Kobbe, Rene Santer, Till Koch, Anahita Fathi, My L. Ly, Stefan Schmiedel, Peter H. Seeberger,, Marylyn M. Addo, Felix F. Loeffler



ABSTRACT
SARS-CoV-2 is the causative agent of COVID-19 and is a severe threat to global health. Patients infected with SARS-CoV-2 show a wide range of symptoms and disease severity, while limited data is available on its immunogenicity. Here, the kinetics of the development of SARS-CoV-2-specific antibody responses in relation to clinical features and dynamics of specific B-cell populations are reported. Immunophenotyping of B cells was performed by flow cytometry with longitudinally collected PBMCs. In parallel, serum samples were analyzed for the presence of SARS-CoV-2-specific IgA, IgG, and IgM antibodies using whole proteome peptide microarrays. Soon after disease onset in a mild case, we observed an increased frequency of plasmablasts concomitantly with a strong SARS-CoV-2-specific IgA response. In contrast, a case with more severe progression showed a delayed, but eventually very strong and broad SARS-CoV-2-specific IgA response. This case study shows that determining SARS-CoV-2-specific antibody epitopes can be valuable to monitor the specificity and magnitude of the early B-cell response, which could guide the development of vaccine candidates. Follow-up studies are required to evaluate whether the kinetics and strength of the SARS-CoV-2-specific IgA response could be potential prognostic markers of viral control.

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17/04/2020 Medical News & Perspectives
The Promise and Peril of Antibody Testing for COVID-19

JAMA

Authors
JENNIFER ABBASI

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17/04/2020 Perspectives
Covid-19 and Immunity in Aging Populations — A New Research Agenda

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Wayne C. Koff, Michelle A. Williams

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17/04/2020 Editorial
Surviving COVID-19: A disease tolerance perspective

Science

Authors
Janelle S. Ayres

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17/04/2020 Articles
Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlate...

Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with...

OXFORD ACADEMY

Authors
Xiaohua Chen, Binghong Zhao, Yueming Qu, Yurou Chen, Jie Xiong, Yong Feng, Dong Men, Qianchuan Huang, Ying Liu, Bo Yang, Jinya Ding, Feng Li

Background

Although the detection of SARS-CoV-2 viral load in respiratory specimens has been widely used to diagnose coronavirus disease-19 (COVID-19), it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of COVID-19 patients. However, it is not clear whether testing for RNAaemia is correlated with the occurrence of cytokine storms or with the specific class of patients.

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16/04/2020 Letter
16/04/2020</i> <u class="PurpleBG">Letter</u&...

16/04/2020 Letter
CRISPR–Cas12-based detection of SARS-CoV-2

NATURE BIOTECHNOLOGY

Authors
AA.VV.

ABSTRACT

An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to produce a global pandemic. We report development of a rapid (<40 min), easy-to-implement and accurate CRISPR–Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US Centers for Disease Control and Prevention SARS-CoV-2 real-time RT–PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.

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16/04/2020 Articles
A serological assay to detect SARS-CoV-2 seroconversion in humans

MEDRXIV

Authors
Fatima Amanat, Daniel Stadlbauer, Shirin Strohmeier, Thi Nguyen, Veronika Chromikova, Meagan McMahon, Kaijun Jiang, Guha Asthagiri-Arunkumar, Denise Jurczyszak, Jose Polanco, Maria Bermudez-Gonzalez, Giulio Kleiner, Teresa Aydillo, Lisa Miorin, Daniel Fierer, Luz Amarilis Lugo, Erna Milunka Kojic, Jonathan Stoever, Sean T.H. Liu, Charlotte Cunningham-Rundles, Philip L. Felgner, Daniel Caplivski, Adolfo Garcia-Sastre, Allen Cheng, Katherine Kedzierska, Olli Vapalahti, View ORCID ProfileJussi Hepojoki, Viviana Simon, Florian Krammer, Thomas Moran

ABSTRACT

SARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. Here we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. Using negative control samples representing pre-COVID 19 background immunity in the general adult population as well as samples from COVID19 patients, we demonstrate that these assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as two days post COVID19 symptoms onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. Such serological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of coronavirus SARS-Cov-2 antibody titers may, in the future, also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.

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10/04/2020 Articles
Handling and Processing of Blood Specimens from Patients with COVID-19...

Handling and Processing of Blood Specimens from Patients with COVID-19 for...

CYTOMETRY

Authors
Andrea Cossarizza, Lara Gibellini, Sara De Biasi, Domenico Lo Tartaro, Marco Mattioli, Annamaria Paolini, Lucia Fidanza, Caterina Bellinazzi, Rebecca Borella, Ivana Castaniere, Marianna Meschiari, Marco Sita, Gianrocco Manco, Enrico Clini, Roberta Gelmini, Massimo Girardis, Giovanni Guaraldi, Cristina Mussini

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08/04/2020 Correspondence
Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Peking Union Medical College Hospital, Beijing, China

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06/04/2020 Research Highlights
In the eye of the COVID-19 cytokine storm

Nature Review

Authors
Natalie Vaninov

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04/04/2020 World Report
Developing antibody tests for SARS-CoV-2

The Lancet

Authors
Anna Petherick

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02/04/2020 Articles
Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronavirus...

Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses

Trends in Immunolog

Authors
Shibo Jiang, Christopher Hillyer, Lanying Du

ABSTRACT
Coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) is threatening global public health, social stability, and economic development. To meet this challenge, this article discusses advances in the research and development of neutralizing antibodies (nAbs) for the prevention and treatment of infection by SARS-CoV-2 and other human CoVs.

Keywords human coronaviruses / SARS-CoV-2 / SARS-CoV / MERS-CoV /neutralizing antibodies

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30/03/2020 Review
The Role of Cytokines including Interleukin-6 in COVID-19 induced...

ELSEVIER

Authors
Dennis McGonagle, Kassem Sharifa, Anthony O'Regand, Charlie Bridgewooda

ABSTRACT

Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.

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28/03/2020 Abstract
Antibody responses to SARS-CoV-2 in patients of novel coronavirus dise...

Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019

NCBI

Authors
Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, Wang X, Yuan J, Li T, Li J, Qian S, Hong C, Wang F, Liu Y, Wang Z, He Q, Li Z, He B, Zhang T, Fu Y, Ge S, Liu L, Zhang J, Xia N, Zhang Z

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25/03/2020 Correspondence
Duration of serum neutralizing antibodies for SARS-CoV-2: Lessons from...

Duration of serum neutralizing antibodies for SARS-CoV-2: Lessons from SARS-CoV infection

Elsevier

Authors
Qingqing Lin, Li Zhu, Zuowei Ni, Haitao Meng, Liangshun You

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23/03/2020 Link
Coronavirus tests: researchers chase new diagnostics to fight the pand...

Coronavirus tests: researchers chase new diagnostics to fight the pandemic

Nature Research

Authors
Nidhi Subbaraman

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21/03/2020 Articles
Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease...

Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)

Oxford University Press

Authors
Li Guo, Lili Ren, Siyuan Yang, Meng Xiao, De Chang, Fan Yang, Charles S Dela Cruz, Yingying Wang, Chao Wu, Yan Xiao, Lulu Zhang, Lianlian Han, Shengyuan Dang, Yan Xu, Qiwen Yang, Shengyong Xu, Huadong Zhu, Yingchun, Qi Jin, Lokesh Sharma, Linghang Wang, Jianwei Wang

Background
Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Current method of detection involves qPCR-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We here aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19.

Methods
The host humoral response against SARS-CoV-2 including IgA, IgM and IgG response were examined by using an ELISA based assay on the recombinant viral nucleocapsid protein. Total 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but had typical manifestation). The diagnostic value of IgM was evaluated in this cohort.

Results
The median duration of IgM and IgA antibody detection were 5 days (IQR 3-6), while IgG was detected on 14 days (IQR 10-18) after symptom onset, with a positive rate of 85.4%, 92.7% and 77.9% respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR method after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combined IgM ELISA assay with PCR for each patient compare with a single qPCR test (51.9%).

Conclusions
Humoral response to SARS-CoV-2 can aid to the diagnosis of COVID-19, including subclinical cases.

novel coronavirus, COVID-19, antibody, ELISA, diagnosis

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17/03/2020 Articles
Risk Factors of Healthcare Workers with Corona Virus Disease 2019: A R...

Risk Factors of Healthcare Workers with Corona Virus Disease 2019: A Retrospective Cohort Study...

Oxford University Press

Authors
Li Ran, Xuyu Chen, Ying Wang, Wenwen Wu, Ling Zhang, Xiaodong Tan

Corona Virus Disease 2019 (COVID-19) originated in Wuhan, China has caused many healthcare workers (HCWs) infected. Seventy-two HCWs manifested with acute respiratory illness were retrospectively enrolled to analyze the risk factors. The high-risk department, longer duty hours, and suboptimal hand hygiene after contacting with patients were linked to COVID-19.

risk factors, COVID-19, healthcare workers

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16/03/2020 Correspondence
Breadth of concomitant immune responses prior to patient recovery: a c...

Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19

NatureMedicine

Authors
Irani Thevarajan, Thi H. O. Nguyen, Marios Koutsakos, Julian Druce, Leon Caly, Carolien E. van de Sandt, Xiaoxiao Jia, Suellen Nicholson, Mike Catton4, Benjamin Cowie, Steven Y. C. Tong, Sharon R. Lewin, Katherine Kedzierska

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16/03/2020 Articles
Substantial undocumented infection facilitates the rapid dissemination...

Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)

Science

Authors
Ruiyun Li, Sen Pei, Bin Chen, Yimeng Song, Tao Zhang, Wan Yang, Jeffrey Shaman

ABSTRACT
Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.

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13/03/2020 Articles
Pathogenic T cells and inflammatory monocytes incite inflammatory stor...

Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients

Oxford University Press

Authors
Yonggang Zhou, Binqing Fu, Xiaohu Zheng, Dongsheng Wang, Changcheng Zhao, Yingjie qi, Rui Sun, Zhigang Tian, Xiaoling Xu, Haiming Wei

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13/03/2020 Viewpoint
The convalescent sera option for containing COVID-19

JCI The Journal of Clinical Investigation

Authors
Arturo Casadevall, Liise-anne Pirofski

As of early 2020, humanity is confronting a pandemic in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 causes coronavirus disease, abbreviated as COVID-19. At the time of this writing, SARS-CoV-2 is spreading in multiple countries, threatening a pandemic that will affect billions of people. This virus appears to be a new human pathogen. Currently there are no vaccines, monoclonal antibodies (mAbs), or drugs available for SARS-CoV-2, although many are in rapid development and some may be available in a short time. This Viewpoint argues that human convalescent serum is an option for prevention and treatment of COVID-19 disease that could be rapidly available when there are sufficient numbers of people who have recovered and can donate immunoglobulin-containing serum. Passive antibody therapy Passive antibody therapy involves the administration of antibodies against a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease due to that agent. In contrast, active vaccination requires the induction of an immune response that takes time to develop and varies depending on the vaccine recipient. Thus, passive antibody administration is the only means of providing immediate immunity to susceptible persons. Passive antibody therapy has a storied history going back to the 1890s and was the only means of treating certain infectious diseases prior to the development of antimicrobial therapy in [...]

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12/03/2020 Correspondence
SARS-CoV-2 RNA more readily detected in induced sputum than in throat ...

SARS-CoV-2 RNA more readily detected in induced sputum than in throat swabs of convalescent COVID-19 patients

The Lancet

Authors
Huanqin Han, Qingfeng Luo, Fan Mo, Lieming Long, Weiqiang Zheng

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27/02/2020 Articles
Development and Clinical Application of A Rapid IgM-IgG Combined Antib...

Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis

Wiley Online Library

Authors
Zhengtu Li, Yongxiang Yi, Xiaomei Luo, Nian Xiong, Yang Liu, Shaoqiang Li,Ruilin Sun, Yanqun Wang, Bicheng Hu, Wei Chen, Yongchen Zhang, Jing Wang, Baofu Huang, Ye Lin, Jiasheng Yang, Wensheng Cai, Xuefeng Wang, Jing Cheng, Zhiqiang Chen, Kangjun Sun, Weimin Pan, Zhifei Zhan, Liyan Chen, Feng Ye

The outbreak of the novel coronavirus disease (COVID-19) quickly spread all over China and to more than 20 other countries. Although the virus (SARS-Cov-2) nucleic acid RT- PCR test has become the standard method for diagnosis of SARS-CoV-2 infection, these real-time PCR test kits have many limitations. In addition, high false negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients.
We have developed a rapid and simple point-of-care lateral flow immunoassay which can detect IgM and IgG antibodies simultaneously against SARS-CoV-2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID-19 patients and 128 negative patients at 8 different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood.
The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.

COVID-19, SARS-CoV-2 Virus Infection, Lateral flow immunoassay, rapid IgM-IgG Combined test, fingerstick blood, Point-of-Care Testing

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26/02/2020 Review
Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019...

MDPI

Authors
Junxiong Pang et all.

ABSTRACT
Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are

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06/02/2020 Correspondence
Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Ge...

Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

The New England Journal of Medicine

Authors
Camilla Rothe, Mirjam Schunk, Peter Sothmann, Gisela Bretzel, Guenter Froeschl, Claudia Wallrauch, Thorbj&ouml;rn Zimmer, Verena Thiel, Christian Janke, Wolfgang Guggemos, Michael Seilmaier, Christian Drosten, Patrick Vollmar, Katrin Zwirglmaier, Sabine Zange, Roman W&ouml;lfel, Michael Hoelscher

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31/01/2020 Articles
Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outb...

Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia

OXFORD ACADEMY

Authors
Daniel K W Chu, Yang Pan, Samuel M S Cheng, Kenrie P Y Hui, Pavithra Krishnan, Yingzhi Liu, Daisy Y M Ng, Carrie K C Wan, Peng Yang, Quanyi Wang, Malik Peiris

BACKGROUND: A novel coronavirus of zoonotic ori- gin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are ur- gently needed for early identification of infected patients. METHODS: We developed two 1-step quantitative real- time reverse-transcription PCR assays to detect two dif- ferent regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, re- spiratory specimens from two 2019-nCoV-infected patients were tested. RESULTS: Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x104-2000 TCID50/re- action). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control sam- ples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. CONCLUSIONS: The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.

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23/01/2020 Articles
Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

NCBI

Authors
Victor M Corman, Olfert Landt, Marco Kaiser, Richard Molenkamp, Adam Meijer, Daniel KW Chu, Tobias Bleicker, Sebastian Br&uuml;nink, Julia Schneider, Marie Luisa Schmidt, Daphne GJC Mulders, Bart L Haagmans, Bas van der Veer, Sharon van den Brink, Lisa Wijsman, Gabriel Goderski, Jean-Louis Romette, Joanna Ellis, Maria Zambon, Malik Peiris, Herman Goossens, Chantal Reusken, Marion PG Koopmans, Christian Drosten

The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a chal- lenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim: We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material avail- able. Methods: Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavi- rus, making use of synthetic nucleic acid technology. Results: The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control mate- rial is made available through European Virus Archive – Global (EVAg), a European Union infrastructure pro- ject. Conclusion: The present study demonstrates the enormous response capacity achieved through coordi- nation of academic and public laboratories in national and European research networks.

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