Sera Neutralizing Activities Against Severe Acute Respiratory Syndrome Coronavirus 2 and Multiple Variants 6 Months After Hospitalization for Coronavirus Disease 2019
Authors: Betton Maureen , Livrozet Marine , Planas Delphine , Fayol Antoine , Monel Blandine , Védie Benoit , Bruel Timothée , Tartour Eric , Robillard Nicolas , Manuguerra Jean-Claude , Blanchard Anne , Ghosn Jade , Visseaux Benoit , Péré Hélène , Lebeaux David , Schwartz Olivier , Veyer David , Hulot Jean-Sébastien ,   French COVID Cohort Study Group, 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 
Published: April 2021

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.