Antibody persistence in the first 6 months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study

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.

Keywords: Antibody persistence; COVID-19; Humoral immunity; Long-term immunity; Long-term protection; Persistence; SARS-CoV-2.

Fig. 1

Study flowchart. COVID-19, coronavirus disease 2019; RT-PCR, reverse-transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. ∗One patient was diagnosed with COVID-19 by RT-PCR during the peak of the outbreak. Viral load was very low (cyclethreshold [CT] value 37). Her antibody response and her memory B-cells were negative at 1 month using flow cytometry. Repeattesting of the original diagnostic nasopharyngeal swab was negative.#missing data for two participants

Fig. 2

Evolution of (A) anti-RBD (anti-receptor binding domain of viral spike protein), (B) anti-N (anti-viral nucleoprotein), and (C) surrogate virus neutralization assay (sVNT) between 1, 3 and 6 months following infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COI, cut-off index; RT-PCR, reverse-transcription polymerase chain reaction. The bars represent the geometric mean concentration (GMC) with 95% confidence interval. The dashed lines represent the respective assays cut-offs.

Fig. 3

Reverse cumulative distribution curves for (A) anti-RBD (anti-receptor binding domain of viral spike protein), (B) anti-N (anti-viral nucleoprotein), and (C) surrogate virus neutralization assay (sVNT) at 1, 3 and 6 months following infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COI, cut-off index; RT-PCR, reverse-transcription polymerase chain reaction. The dashed lines represent the respective assays cut-offs.