Antibody persistence in the first six months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study

L’Huillier, Arnaud G.; Meyer, Benjamin; Andrey, Diego O.; Arm-Vernez, Isabelle; Baggio, Stephanie; Didierlaurent, Arnaud; Eberhardt, Christiane S.; Eckerle, Isabella; Grasset-Salomon, Carole; Huttner, Angela; Posfay-Barbe, Klara M.; Royo, Irene Sabater; Pralong, Jacques A.; Vuilleumier, Nicolas; Yerly, Sabine; Siegrist, Claire-Anne; Kaiser, Laurent

OBJECTIVE: To longitudinally evaluate the persistence of humoral immunity up to six months in a cohort of hospital employees with mild COVID-19. METHODS: We measured anti-RBD, -N and neutralizing antibodies at one, three and six months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay. RESULTS: SARS-CoV-2-specific antibodies persisted in all participants up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between month one (74(.)2 U/ml [95%CI 62(.)7-87(.)8), three (103(.)2 U/ml [95%CI 87(.)9-121(.)2]; p<0(.)001), and six (123(.)3 U/ml [95%CI 103(.)4-147(.)0]; p<0(.)001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% (195/196) of participants at six months post infection. Their GMC progressively decreased between months one (20(.)1 AU/ml [95%CI 16(.)9-24(.)0]), three (15(.)2 AU/ml [95%CI 13(.)2-17(.)6]; p<0(.)001) and six (9(.)4 AU/ml [95%CI 7(.)7-11(.)4]; p<0(.)001). RBD-ACE2 inhibiting antibody titers and anti-RBD antibody concentrations strongly correlated at each timepoint (all r>0(.)86, p<0(.)001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2 inhibiting antibody titers, but not with their kinetics. CONCLUSION: Neutralizing antibodies persisted at six months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.