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

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.

Figure 1:

A) UMAP of cells obtained from patients with mild and severe COVID-19, as well as healthy control subjects. Each point represents a single cell. B) Dot plots showing expression of B cell marker genes for naive, memory, and plasmablast B cell subsets for the clusters identified in panel A.

Figure 2:

Frequency of B cell subtypes and unmutated B cell clones in all patient cohorts. A) Naive (clusters 0, 1, 3, 5), plasmablast (cluster 7), and memory (clusters 2, 4, 6) B cell frequencies among total B cells in each cohort. B) Clonal diversity of each B cell subset in each cohort. To account for differences in sequence depth among samples, Simpson’s diversity was calculated as the mean over 1000 resampling realizations to a uniform sequence depth among samples and cell type. C) Proportion of IgG B cell clones that are unmutated (median SHM < 1%) in each cohort. The proportion of unmutated IgG clones was not considered for cells within naive B cell clusters, because these likely represent a small number of mis-clustered cells (Supplemental Fig. 3A). P values in all panels were calculated using a Wilcoxon test.