ABSTRACT
OBJECTIVES: To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19). METHODS: We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay. RESULTS: Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2;p < 0.001), and 6 (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% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6;p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4;p < 0.001). RBD-ACE2-inhibiting antibody titres 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 titres, but not with their kinetics. CONCLUSIONS: Neutralizing antibodies persisted at 6 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.
ABSTRACT
Background: Little is known about the duration and breadth of humoral immunity against SARS-CoV-2 to better inform appropriate pandemic control measures.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.Findings: Anti-RBD antibodies were detected in all participants at each timepoint. 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 92 . 5% (184/199), 94 . 4% (185/196) and 76 . 5% (150/196) participants at one, three and six months, respectively. 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). Neutralizing antibody and anti-RBD concentrations strongly correlated at each timepoint (all r>0 . 86, p<0 . 001). Disease severity was associated with higher initial anti-RBD and neutralizing concentrations, but not with their kinetics.Interpretation: Neutralizing antibodies persisted at six months in most 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. Trial Registration: registered (NCT04329546)Funding: Pictet, Ancrage and Schmidheiny Foundations, Geneva University Hospitals’ Private Foundation, PRD, Center for Vaccinology and Centre for Emerging Viral Diseases.Declaration of Interests: The authors have no conflict of interest.Ethics Approval Statement: The study was approved by the local ethics committee (CCER 2020-00516) and registered (NCT04329546) prior to initiation. All hospital workers provided written informed consent before enrolment.