Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection

Background: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enr...

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Main Authors: Floriane Gallais, Pierre Gantner, Timothée Bruel, Aurélie Velay, Delphine Planas, Marie-Josée Wendling, Sophie Bayer, Morgane Solis, Elodie Laugel, Nathalie Reix, Anne Schneider, Ludovic Glady, Baptiste Panaget, Nicolas Collongues, Marialuisa Partisani, Jean-Marc Lessinger, Arnaud Fontanet, David Rey, Yves Hansmann, Laurence Kling-Pillitteri, Olivier Schwartz, Jérome De Sèze, Nicolas Meyer, Maria Gonzalez, Catherine Schmidt-Mutter, Samira Fafi-Kremer
Format: Article
Language:English
Published: Elsevier 2021-09-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396421003546
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author Floriane Gallais
Pierre Gantner
Timothée Bruel
Aurélie Velay
Delphine Planas
Marie-Josée Wendling
Sophie Bayer
Morgane Solis
Elodie Laugel
Nathalie Reix
Anne Schneider
Ludovic Glady
Baptiste Panaget
Nicolas Collongues
Marialuisa Partisani
Jean-Marc Lessinger
Arnaud Fontanet
David Rey
Yves Hansmann
Laurence Kling-Pillitteri
Olivier Schwartz
Jérome De Sèze
Nicolas Meyer
Maria Gonzalez
Catherine Schmidt-Mutter
Samira Fafi-Kremer
author_facet Floriane Gallais
Pierre Gantner
Timothée Bruel
Aurélie Velay
Delphine Planas
Marie-Josée Wendling
Sophie Bayer
Morgane Solis
Elodie Laugel
Nathalie Reix
Anne Schneider
Ludovic Glady
Baptiste Panaget
Nicolas Collongues
Marialuisa Partisani
Jean-Marc Lessinger
Arnaud Fontanet
David Rey
Yves Hansmann
Laurence Kling-Pillitteri
Olivier Schwartz
Jérome De Sèze
Nicolas Meyer
Maria Gonzalez
Catherine Schmidt-Mutter
Samira Fafi-Kremer
author_sort Floriane Gallais
collection DOAJ
description Background: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. Fun1ding: None.
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spelling doaj.art-6f780245a7cb44fc98d49b590d874b362022-12-21T21:34:55ZengElsevierEBioMedicine2352-39642021-09-0171103561Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfectionFloriane Gallais0Pierre Gantner1Timothée Bruel2Aurélie Velay3Delphine Planas4Marie-Josée Wendling5Sophie Bayer6Morgane Solis7Elodie Laugel8Nathalie Reix9Anne Schneider10Ludovic Glady11Baptiste Panaget12Nicolas Collongues13Marialuisa Partisani14Jean-Marc Lessinger15Arnaud Fontanet16David Rey17Yves Hansmann18Laurence Kling-Pillitteri19Olivier Schwartz20Jérome De Sèze21Nicolas Meyer22Maria Gonzalez23Catherine Schmidt-Mutter24Samira Fafi-Kremer25CHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, FranceCHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, FranceVirus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR Paris 3569, France; Vaccine Research Institute, Creteil, FranceCHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, FranceVirus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR Paris 3569, France; Vaccine Research Institute, Creteil, FranceCHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, FranceCHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, Strasbourg F-67091, FranceCHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, FranceCHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, FranceCHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, Strasbourg F-67091, FranceCHU de Strasbourg, Département de Génétique Moléculaire du Cancer, Strasbourg F-67091, FranceCHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, Strasbourg F-67091, FranceCHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, FranceCHU de Strasbourg, Center d'Investigation Clinique INSERM CIC 1434, Strasbourg F-67091, FranceCHU de Strasbourg, Trait d'Union, Strasbourg F-67091, FranceCHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, Strasbourg F-67091, FranceDepartment of Global Health, Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France; PACRI Unit, Conservatoire National des Arts et Métiers, Paris, FranceCHU de Strasbourg, Trait d'Union, Strasbourg F-67091, FranceCHU de Strasbourg, Service des Maladies Infectieuses et Tropicales, Strasbourg F-67091, FranceCHU de Strasbourg, Service de Pathologies Professionnelles, Strasbourg F-67091, FranceVirus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR Paris 3569, France; Vaccine Research Institute, Creteil, FranceCHU de Strasbourg, Center d'Investigation Clinique INSERM CIC 1434, Strasbourg F-67091, FranceCHU de Strasbourg, Service de santé Publique, GMRC, Strasbourg F-67091, FranceCHU de Strasbourg, Service de Pathologies Professionnelles, Strasbourg F-67091, FranceCHU de Strasbourg, Center d'Investigation Clinique INSERM CIC 1434, Strasbourg F-67091, FranceCHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, France; Corresponding author at: Institut de Virologie, 3 rue Koeberlé, Strasbourg, 67000, France.Background: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. Fun1ding: None.http://www.sciencedirect.com/science/article/pii/S2352396421003546SARS-CoV-2COVID-19ImmunityNeutralizing antibodiesReinfection
spellingShingle Floriane Gallais
Pierre Gantner
Timothée Bruel
Aurélie Velay
Delphine Planas
Marie-Josée Wendling
Sophie Bayer
Morgane Solis
Elodie Laugel
Nathalie Reix
Anne Schneider
Ludovic Glady
Baptiste Panaget
Nicolas Collongues
Marialuisa Partisani
Jean-Marc Lessinger
Arnaud Fontanet
David Rey
Yves Hansmann
Laurence Kling-Pillitteri
Olivier Schwartz
Jérome De Sèze
Nicolas Meyer
Maria Gonzalez
Catherine Schmidt-Mutter
Samira Fafi-Kremer
Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection
EBioMedicine
SARS-CoV-2
COVID-19
Immunity
Neutralizing antibodies
Reinfection
title Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection
title_full Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection
title_fullStr Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection
title_full_unstemmed Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection
title_short Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection
title_sort evolution of antibody responses up to 13 months after sars cov 2 infection and risk of reinfection
topic SARS-CoV-2
COVID-19
Immunity
Neutralizing antibodies
Reinfection
url http://www.sciencedirect.com/science/article/pii/S2352396421003546
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