Impact of host immune status on discordant anti‐sars‐cov‐2 circulating b cell frequencies and antibody levels

Abstract

Individuals with pre‐existing chronic systemic low‐grade inflammation are prone to de-velop severe COVID‐19 and stronger anti‐SARS‐CoV‐2 antibody responses. Whether this phenom-enon reflects a differential expansion of antiviral B cells or a failure to regulate antibody synthesis remains unknown. Here, we compared the antiviral B cell repertoire of convalescent healthcare personnel to that of hospitalized patients with pre‐existing comorbidities. Out of 277,500 immortalized B cell clones, antiviral B cell frequencies were determined by indirect immunofluorescence screen-ing on SARS‐CoV‐2 infected cells. Surprisingly, frequencies of SARS‐CoV‐2 specific clones from the two groups were not statistically different, despite higher antibody levels in hospitalized patients. Moreover, functional analyses revealed that several B cell clones from healthcare personnel with low antibody levels had neutralizing properties. This study reveals for the first time a key qualita-tive defect of antibody synthesis in severe patients and calls for caution regarding estimated protective immunity based only on circulating antiviral antibodies.