Long-term evolution of humoral immune response after SARS-CoV-2 infection

OBJECTIVE: We aimed to characterize the evolution of humoral immune response up to 1 year after SARS-CoV-2 infection in healthcare workers (HCWs) during the first wave of COVID-19 in Paris. METHODS: Serum samples from 92 HCWs were tested at month 0 (M0), M6, and M12 after SARS-CoV-2 infection for IgG targeting the nucleocapsid (N), IgG targeting the receptor-binding domain (RBD) of spike (S) protein, IgA targeting S, and anti-RBD neutralizing antibodies. After M6, 46 HCWs received a single dose of COVID-19 vaccine. RESULTS: We observed a significant decrease in all SARS-CoV-2 immunologic markers at M6 post-infection: median decreases were 0.26 log binding antibody units/mL (M0: 1.9 (interquartile range (IQR) 1.47–2.27); M6: 1.64 (IQR 1.22–1.92)) for anti-RBD IgG; 4.10 (index) (M0: 4.94 (IQR 2.72–6.82); M6: 0.84 (IQR 0.25–1.55)) for anti-N IgG; 0.64 (index) (M0: 2.50 (IQR 1.18–4.62); M6: 1.86 (IQR 0.85–3.54)) for anti-S IgA; and 24.4% (M0: 66.4 (IQR 39.7–82.5); M6: 42.0 (IQR 16.8–68.8)) inhibition activity for the RBD neutralizing antibodies. Between M6 and M12, anti-RBD IgG level, anti-S IgA index, and anti-RBD neutralizing activity significantly increased among COVID-19 vaccinated HCWs, whereas they remained stable among unvaccinated HCWs. Anti-N IgG index significantly decreased between M6 and M12 among both vaccinated (median: 0.73 (IQR 0.23–1.11) at M6 and 0.52 (IQR 0.20–0.73) at M12) and unvaccinated HCWs (median: 0.79 (IQR 0.21–4.67) at M6 and 0.34 (IQR 0.24–2.78) at M12). DISCUSSION: A steady decline in the anti-N IgG response was observed during the first year after SARS-CoV-2 infection among HCWs, whereas the anti-RBD IgG and the anti-S IgA responses remained stable and could be enhanced by COVID-19 vaccination.