Sera Neutralizing Activities Against Severe Acute Respiratory Syndrome Coronavirus 2 and Multiple Variants 6 Months After Hospitalization for Coronavirus Disease 2019

Author:

Betton Maureen12,Livrozet Marine12,Planas Delphine34,Fayol Antoine12,Monel Blandine3,Védie Benoit5,Bruel Timothée3,Tartour Eric6,Robillard Nicolas7,Manuguerra Jean-Claude8,Blanchard Anne2,Ghosn Jade910,Visseaux Benoit1011,Péré Hélène12,Lebeaux David7,Schwartz Olivier34,Veyer David711,Hulot Jean-Sébastien12ORCID,Abel Laurent,Andrejak Claire,Angoulvant François,Bachelet Delphine,Bhavsar Krishna,Bouadma Lila,Chair Anissa,Couffignal Camille,da Silveira Charlene,Debray Marie-Pierre,Descamps Diane,Duval Xavier,Eloy Philippine,Esposito-Farese Marina,Ettalhaoui Nadia,Gault Nathalie,Ghosn Jade,Gorenne Isabelle,Hoffmann Isabelle,Kafif Ouifiya,Kali Sabrina,Khalil Antoine,Laouénan Cédric,Laribi Samira,Le Minh,Le Hingrat Quentin,Lescure François-Xavier,Lucet Jean Christophe,Mentré France,Mullaert Jimmy,Peiffer-Smadja Nathan,Peytavin Gilles,Roy Carine,Schneider Marion,Si Mohammed Nassima,Tagherset Lysa,Tardivon Coralie,Tellier Marie-Capucine,Timsit Jean-François,Trioux Théo,Tubiana Sarah,Visseaux Benoit,Yazdanpanah Yazdan,Basmaci Romain,Picone Olivier,Behilill Sylvie,van der Werf Sylvie,Enouf Vincent,Mouquet Hugo,Beluze Marine,Benkerrou Dehbia,Dorival Céline,Téoulé François,Meziane Amina,Bompart François,Bouscambert Maude,Cervantes-Gonzalez Minerva,d’Ortenzio Eric,Puéchal Oriane,Semaille Caroline,Chirouze Catherine,Coelho Alexandra,Couffin-Cadiergues Sandrine,Esperou Hélène,Houas Ikram,Jaafoura Salma,Papadopoulos Aurélie,Deplanque Dominique,Desvallée Mathilde,Khan Coralie,Diallo Alpha,Bartoli Marie,Le Mestre Soizic,Mercier Noémie,Paul Christelle,Petrov-Sanchez Ventzislava,Diouf Alphonsine,Hoctin Alexandre,Mambert Marina,Dubos François,Etienne Manuel,Gaymard Alexandre,Gigante Tristan,Gilg Morgane,Rossignol Bénédicte,Guedj Jérémie,Le Nagard Hervé,Lingas Guillaume,Neant Nadège,Hulot Jean-Sébastien,Kaguelidou Florentia,Pages Justine,Levy Yves,Wiedemann Aurélie,Levy-Marchal Claire,Lina Bruno,Rosa-Calatrava Manuel,Terrier Olivier,Malvy Denis,Noret Marion,Rossignol Patrick,Tual Christelle,Veislinger Aurélie,Vanel Noémie,

Affiliation:

1. Université de Paris, Inserm, Paris-Centre de Recherche Cardiovasculaire (PARCC), Paris, France

2. Centre d’investigation clinique (CIC1)418 and Département médico-universitaire Cardiologie Rein Transplantation Neurovasculaire (DMU CARTE), Assistance Publique–Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Paris, France

3. Virus and Immunity Unit, Department of Virology, Institut Pasteur, Centre national de la recherche scientifique (CNRS) UMR 3569, 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, Assistance Publique–Hôpitaux de Paris, Paris, France

6. Department of Immunology, Hôpital Européen Georges Pompidou, Assistance Publique–Hôpitaux de Paris, Paris, France

7. Service de Microbiologie, Hôpital Européen Georges Pompidou, Assistance Publique–Hôpitaux de Paris, Paris, France

8. Institut Pasteur, Cellule d’Intervention Biologique d’Urgence, Paris, France

9. Infectious and Tropical Diseases Department, Hôpital Bichat Claude Bernard, Assistance Publique–Hôpitaux de Paris, Paris, France

10. Université de Paris, Infection, Antimicrobien, Modélisation, Evolution (IAME), Inserm, Paris, France

11. Assistance Publique–Hôpitaux de Paris, Bichat Claude Bernard Hospital, Virology Department, Paris, France

12. Functional Genomics of Solid Tumors, Inserm, Centre de Recherche des Cordeliers, Université de Paris and Sorbonne Université, Paris, France

Abstract

Abstract Background Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized. Methods In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG). Results Levels of seroneutralization 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 seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to 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 the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant. Conclusions Decrease in 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.

Funder

French Ministry of Health

Institut Pasteur

Fondation pour la Recherche Médicale

Agence Nationale de Recherche sur le Sida et les hépatites virales

Vaccine Research Institute

IDISCOVR

Assistance Publique–Hôpitaux de Paris

Inserm

French National Research Agency

Fédération Française de Cardiologie

Leducq Foundation

University Research Federation

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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