Durable SARS-CoV-2 B cell immunity after mild or severe disease.

Abstract

Multiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-specific MBC in cohorts of ambulatory COVID-19 patients with mild disease (n = 7), and hospitalized patients with moderate to severe disease (n = 7), at a median of 54 (39-104) days after symptom onset. We detected S-RBD-specific class-switched MBC in 13 of 14 participants, failing only in the individual with lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBC (rMBC) made up the largest proportion of S-RBD-specific MBC in both cohorts. FCRL5, a marker of functional memory on rMBC, was more dramatically upregulated on S-RBD-specific rMBC after mild infection than after severe infection. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched rMBC that resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after mild or severe disease.