Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19.

Hoehn, Kenneth B; Ramanathan, Palaniappan; Unterman, Avraham; Sumida, Tomokazu S; Asashima, Hiromitsu; Hafler, David A; Kaminski, Naftali; Dela Cruz, Charles S; Sealfon, Stuart C; Bukreyev, Alexander; Kleinstein, Steven H

Protective immunity against COVID-19 likely depends on the production of SARS-CoV-2-specific plasma cells and memory B cells postinfection or postvaccination. Previous work has found that germinal center reactions are disrupted in severe COVID-19. This may adversely affect long-term immunity against reinfection. Consistent with an extrafollicular B cell response, patients with severe COVID-19 have elevated frequencies of clonally expanded, class-switched, unmutated plasmablasts. However, it is unclear whether B cell populations in individuals with mild COVID-19 are similarly skewed. In this study, we use single-cell RNA sequencing of B cells to show that in contrast to patients with severe COVID-19, subjects with mildly symptomatic COVID-19 have B cell repertoires enriched for clonally diverse, somatically hypermutated memory B cells ∼30 d after the onset of symptoms. This provides evidence that B cell responses are less disrupted in mild COVID-19 and result in the production of memory B cells.