B cell subpopulations were also altered in COVID-19 disease. Whereas naïve B cell frequencies were similar in COVID-19 patients and RD or HD, the frequencies of class-switched (IgD−CD27+) and not-class-switched (IgD+CD27+) memory B cells were significantly reduced (Fig. 4A). Conversely, frequencies of CD27−IgD− B cells and CD27+CD38+ PB were often robustly increased (Fig. 4, A and B). In some cases, PB represented >30% of circulating B cells, similar to levels observed in acute Ebola or Dengue virus infections (42, 43). However, these PB responses were only observed in ~2/3 of patients, with the remaining patients displaying PB frequencies similar to HD and RD (Fig. 4B). KI67 expression was markedly elevated in all B cell subpopulations in COVID-19 patients compared to either control group (Fig. 4C). This observation suggests a role for an antigen-driven response to infection and/or lymphopenia-driven proliferation. Higher KI67 in PB may reflect recent generation in the COVID-19 patients compared to HD or RD. CXCR5 expression was also reduced on all major B cell subsets in COVID-19 patients (Fig. 4D). Loss of CXCR5 was not specific to B cells, however, as expression was also decreased on non-naïve CD4 T cells (Fig. 4E). Changes in the B cell subsets were not associated with co-infection, immune suppression, or treatment with steroids or other clinical features, though a possible negative association of IL-6 and PB was revealed (fig. S5A). These observations suggest that the B cell response phenotype of COVID-19 disease was not simply due to systemic inflammation.