Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19
Kenneth B. Hoehn, Palaniappan Ramanathan, Avraham Unterman, Tomokazu S. Sumida, Hiromitsu Asashima, David A. Hafler, Naftali Kaminski, Charles S. Dela Cruz, Stuart C. Sealfon, Alexander Bukreyev, Steven H. Kleinstein
Abstract
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.