Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

Wheatley, Adam K.; Juno, Jennifer A.; Wang, Jing J.; Selva, Kevin J.; Reynaldi, Arnold; Tan, Hyon-Xhi; Lee, Wen Shi; Wragg, Kathleen M.; Kelly, Hannah G.; Esterbauer, Robyn; Davis, Samantha K.; Kent, Helen E.; Mordant, Francesca L.; Schlub, Timothy E.; Gordon, David L.; Khoury, David S.; Subbarao, Kanta; Cromer, Deborah; Gordon, Tom P.; Chung, Amy W.; Davenport, Miles P.; Kent, Stephen J.

The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4(+) and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG(+) memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.