Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection
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
Affiliations
Floriane Gallais
CHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, France
Pierre Gantner
CHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, France
Timothée Bruel
Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR Paris 3569, France; Vaccine Research Institute, Creteil, France
Aurélie Velay
CHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, France
Delphine Planas
Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR Paris 3569, France; Vaccine Research Institute, Creteil, France
Marie-Josée Wendling
CHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France
Sophie Bayer
CHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, Strasbourg F-67091, France
Morgane Solis
CHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, France
Elodie Laugel
CHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, France
Nathalie Reix
CHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, Strasbourg F-67091, France
Anne Schneider
CHU de Strasbourg, Département de Génétique Moléculaire du Cancer, Strasbourg F-67091, France
Ludovic Glady
CHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, Strasbourg F-67091, France
Baptiste Panaget
CHU de Strasbourg, Laboratoire de Virologie, Strasbourg F-67091, France; Strasbourg University, INSERM, IRM UMR-S 1109, Strasbourg F-67000, France
Nicolas Collongues
CHU de Strasbourg, Center d'Investigation Clinique INSERM CIC 1434, Strasbourg F-67091, France
Marialuisa Partisani
CHU de Strasbourg, Trait d'Union, Strasbourg F-67091, France
Jean-Marc Lessinger
CHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, Strasbourg F-67091, France
Arnaud Fontanet
Department of Global Health, Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France; PACRI Unit, Conservatoire National des Arts et Métiers, Paris, France
David Rey
CHU de Strasbourg, Trait d'Union, Strasbourg F-67091, France
Yves Hansmann
CHU de Strasbourg, Service des Maladies Infectieuses et Tropicales, Strasbourg F-67091, France
Laurence Kling-Pillitteri
CHU de Strasbourg, Service de Pathologies Professionnelles, Strasbourg F-67091, France
Olivier Schwartz
Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR Paris 3569, France; Vaccine Research Institute, Creteil, France
Jérome De Sèze
CHU de Strasbourg, Center d'Investigation Clinique INSERM CIC 1434, Strasbourg F-67091, France
Nicolas Meyer
CHU de Strasbourg, Service de santé Publique, GMRC, Strasbourg F-67091, France
Maria Gonzalez
CHU de Strasbourg, Service de Pathologies Professionnelles, Strasbourg F-67091, France
Catherine Schmidt-Mutter
CHU de Strasbourg, Center d'Investigation Clinique INSERM CIC 1434, Strasbourg F-67091, France
Samira Fafi-Kremer
CHU 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.
