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

Nat Commun. 2021 Feb 19;12(1):1162. doi: 10.1038/s41467-021-21444-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Antibody Formation*
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • COVID-19 / immunology*
  • Humans
  • Immunity, Cellular*
  • Immunoglobulin G / immunology
  • Immunologic Memory*
  • Longitudinal Studies
  • Models, Theoretical
  • Neutralization Tests
  • T-Lymphocytes, Helper-Inducer / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G