Maureen Betton1,2, Marine Livrozet1,2, Delphine Planas3,4, Antoine Fayol1,2, Blandine Monel3, Benoit Védie5, Timothée Bruel3, Eric Tartour6, Nicolas Robillard7, Jean-Claude Manuguerra8, Anne Blanchard2, Jade Ghosn9,10, Benoit Visseaux10,11, Hélène Péré12, David Lebeaux7, Olivier Schwartz3,4, David Veyer7,11, Jean-Sébastien Hulot1,2. 1. Université de Paris, INSERM, PARCC, F-75006 Paris, France. 2. CIC1418 and DMU CARTE, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpital Européen Georges-Pompidou, F-75015, Paris, France. 3. Virus & Immunity Unit, Department of Virology, Institut Pasteur, CNRS UMR3569, Paris France. 4. Vaccine Research Institute, Faculté de Médecine, INSERM U955, Université Paris-Est Créteil, Créteil, France. 5. Laboratoire de Biochimie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. 6. Department of Immunology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. 7. Service de Microbiologie, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris 75015, France. 8. Institut Pasteur, Cellule d'Intervention Biologique d'Urgence, Paris, France. 9. Infectious and Tropical Diseases Department, Hôpital Bichat Claude Bernard, AP-HP, Paris, France. 10. Université de Paris, IAME, INSERM, F-75018 Paris, France. 11. AP-HP, Bichat Claude Bernard Hospital, Virology Department, 75018 Paris, France. 12. Functional Genomics of Solid Tumors (FunGeST), INSERM, Centre de Recherche des Cordeliers, Université de Paris and Sorbonne Université, Paris, France.
Abstract
BACKGROUND: Humoral response to SARS-CoV-2 occurs within the first weeks after COVID-19. Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution overtime after COVID-19 as well as efficiency against novel variants are however poorly characterized. METHODS: In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3- and 6-months post-infection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-Spike (S) and anti-Nucleocapsid (NP) IgG. FINDINGS: Levels of sero-neutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with sero-neutralization and this correlation was stronger for anti-S than for anti-NP antibodies. The level of sero-neutralization quantified at 6 months correlated with markers of initial severity, notably admission in intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against D614G, B.1.1.7 and P.1 variants but a significantly weaker activity against B.1.351 variant. INTERPRETATION: Decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant.
BACKGROUND: Humoral response to SARS-CoV-2 occurs within the first weeks after COVID-19. Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution overtime after COVID-19 as well as efficiency against novel variants are however poorly characterized. METHODS: In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3- and 6-months post-infection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-Spike (S) and anti-Nucleocapsid (NP) IgG. FINDINGS: Levels of sero-neutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with sero-neutralization and this correlation was stronger for anti-S than for anti-NP antibodies. The level of sero-neutralization quantified at 6 months correlated with markers of initial severity, notably admission in intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against D614G, B.1.1.7 and P.1 variants but a significantly weaker activity against B.1.351 variant. INTERPRETATION: Decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant.
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