Clinical course impacts early kinetics, magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection

To understand the determinants of long-term immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the concurrent impact of vaccination and emerging variants, we follow a prospective cohort of 332 patients with coronavirus disease 2019 (COVID-19) over more than a year after symptom onset. We evaluate plasma-neutralizing activity using HIV-based pseudoviruses expressing the spike of different SARS-CoV-2 variants and analyze them longitudinally using mixed-effects models. Longterm neutralizing activity is stable beyond 1 year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short-and long-lived memory B cells, while the responses of non-hospitalized individuals are dominated by long-lived B cells. In both groups, vaccination boosts responses to natural infection. Long-term (>300 days from infection) responses in unvaccinated participants show a reduced efficacy against beta, but not alpha nor delta, variants. Multivariate analysis identifies the severity of primary infection as an independent determinant of higher magnitude and lower relative cross-neutralization activity of long-term neutralizing responses.

Automated summary

This study follows a cohort of 332 COVID-19 patients for over a year to understand the long-term immune responses to SARS-CoV-2. The study finds that long-term neutralizing activity remains stable beyond one year after infection in mild/asymptomatic and hospitalized participants. It also shows that hospitalized individuals generate both short-term and long-term memory B cells, while non-hospitalized individuals have dominant long-term B cells. Vaccination boosts responses to natural infection, but unvaccinated participants show reduced efficacy against the beta variant.