Evolution of antibody immunity to SARS-CoV-2.

Abstract

Severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) has infected 78million individuals and is responsible for over 1.7million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory Bcells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87individuals assessed at 1.3 and 6.2months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory Bcells remains unchanged at 6.2months after infection. Memory Bcells display clonal turnover after 6.2months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4months after the onset of coronavirus disease2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14individuals. We conclude that the memory Bcell response to SARS-CoV-2 evolves between 1.3 and 6.2months after infection in a manner that is consistent with antigen persistence.