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1. Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralization and commercial assays

Author

Fascia Pascal, Adnot Jérôme, Fontaine Juliette, Massardier-Pilonchéry Amélie, Boibieux André, Josset Laurence, Nicolas Guibert, Oria Fatima, Nazare Julie-Anne, Chiarello Pierre, Samperiz Audrey, Antonin Bal, Prudent Mélanie, Simon Chantal, Dulce Alfaiate, Fassier Jean-Baptiste, Florence Morfin-Sherpa, Constance d'Aubarede, Brunel-Dalmas Florence, Lahousse Matthieu, Pitiot Virginie, Trabaud Mary-Anne, Gaillot-Durand Lucie, Bal Antonin, Lina Bruno, Trouillet-Assant Sophie, Gueyffier François, Perry Marielle, Gillet Myriam, Adèle Paul, Jean-Baptiste Fassier, Valette Martine, Bourgeois Gaëlle, Lozano Hélène, Kahina Saker, Alfaiate Dulce, Morfin Florence, Mary-Anne Trabaud, Rabilloud Muriel, Schlienger Isabelle, Narbey David, Durupt François, Makhloufi Djamila, Bruno Pozzetto, Paul Adèle, Caire Eurydice, Bergeret Alain, Godinot Matthieu, Escuret Vanessa, Bonnet Florent, Moll Frédéric, Guibert Nicolas, Gaymard Alexandre, Cotte Laurent, Sophie Trouillet-Assant, Muriel Rabilloud, Virginie Pitiot, Amélie Massardier-Pilonchery, Milon Marie-Paule, Charbotel Barbara, Carole Langlois-Jacques, Bruno Lina, Hospices Civils de Lyon (HCL), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Université de Lyon, Institut des Agents Infectieux [Lyon] (IAI), Service de médecine et santé au travail, hospices civils de Lyon, Laboratoire de virologie, Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)

Subjects
Male, Time Factors, Antibodies, Viral, Neutralization, MEDECINE, Health personnel, 0302 clinical medicine, SANTE, SARS-COV2, Medicine, 030212 general & internal medicine, Letter to the Editor, 0303 health sciences, biology, PERSONNEL DE SANTE, virus diseases, General Medicine, Middle Aged, University hospital, TRAVAIL, 3. Good health, Titer, Infectious Diseases, Female, Antibody, Serological assays, ANTICORPS, Adult, Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Health Personnel, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, GESTION DU PERSONNEL, Virus Neutralization, Virus, 03 medical and health sciences, Neutralization Tests, Seroprevalence, Humans, Healthcare workers, Virus neutralisation assay, 030304 developmental biology, SARS-CoV-2, business.industry, COVID-19, Antibodies, Neutralizing, Virology, Antibody response, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

We conducted a prospective study in healthcare workers (n=296) of the University Hospital of Lyon, France. Serum samples (n=296) collected six months after disease onset were tested using three commercial assays: the Wantai Ab assay detecting total antibodies against the receptor binding domain (RBD) of the S protein, the bioMerieux Vidas assay detecting IgG to the RBD and the Abbott Architect assay detecting IgG to the N protein. The neutralising antibody (NAb) titre was also determined for all samples with a virus neutralisation assay (VNA) using live virus. The positivity rate was 100% with the Wantai assay, 84.8% with the bioMerieux assay and 55.4% with the Abbott assay. Only 51% of HCWs were positive for the presence of NAb. Less than 10 % of HCWs had a NAb titre greater than 80. At a neutralising titre of 80, the area under the curves [IC 95%] was 0.71 [0.62-0.81], 0.75 [0.65-0.85] and 0.95 [0.92-0.97] for Wantai, Abbott and Vidas respectively. The data presented herein suggest that commercial assays detecting antibodies against the N protein must not be used in long-term seroprevalence surveys while the Wantai assay could be useful for this purpose. VNA should remain the gold standard to assess the protective antibody response, but some commercial assays could be used as first-line screening of long-term presence of NAb.

Published
2021
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2. Assessment of serological techniques for screening patients for COVID-19 (COVID-SER): a prospective, multicentric study

Author

Trouillet-Assant, Sophie, Albert Vega, Chloe, Bal, Antonin, Nazare, Julie Anne, Fascia, Pascal, Paul, Adèle, Massardier-Pilonchery, Amélie, d Aubarede, Constance, Guibert, Nicolas, Pitiot, Virginie, Lahousse, Matthieu, Boibieux, André, Makhloufi, Djamila, Simon, Chantal, Rabilloud, Muriel, Trabaud, Mary Anne, Gueyffier, François, Fassier, Jean-Baptiste, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), HCL Groupement Hospitalier Nord [Lyon], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hôpital Henry Gabrielle [CHU - HCL], Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Hôpital Edouard Herriot [CHU - HCL], Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de LyonFondation des Hospices Civils de Lyon, COVID-SER study group: Jérôme Adnot, Dulce Alfaiate, Antonin Bal, Alain Bergeret, André Boibieux, Florent Bonnet, Gaëlle Bourgeois, Florence Brunel-Dalmas, Eurydice Caire, Barbara Charbotel, Pierre Chiarello, Laurent Cotte, Constance d'Aubarede, François Durupt, Escuret Vanessa, Fascia Pascal, Fassier Jean-Baptiste, Fontaine Juliette, Gaillot-Durand Lucie, Gaymard Alexandre, Gillet Myriam, Godinot Matthieu, Gueyffier François, Guibert Nicolas, Josset Laurence, Lahousse Matthieu, Lina Bruno, Lozano Hélène, Makhloufi Djamila, Massardier-Pilonchéry Amélie, Milon Marie-Paule, Moll Frédéric, Morfin Florence, Narbey David, Nazare Julie-Anne, Oria Fatima, Paul Adèle, Perry Marielle, Pitiot Virginie, Prudent Mélanie, Rabilloud Muriel, Samperiz Audrey, Schlienger Isabelle, Simon Chantal, Trabaud Mary-Anne, Trouillet-Assant Sophie, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire

Subjects
Male, SARS-CoV-2, public health, [SDV]Life Sciences [q-bio], COVID-19, General Medicine, Antibodies, Viral, diagnostic microbiology, [SDV] Life Sciences [q-bio], molecular diagnostics, Humans, Mass Screening, Female, Serologic Tests, Public Health, Prospective Studies, Pandemics
Abstract

International audience; INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated. METHODS AND ANALYSIS: We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04341142.

Published
2020
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