A recent study has provided mechanistic insights into how some cases of COVID-19 exhibit low B cell number. Kaneko et al. (2020) studied the post-mortem samples (n = 11) of thoracic lymph nodes and spleens and found that Bcl-6+ germinal center (GC) B cells highly reduced in these patients in comparison to non-COVID-19 control (n = 6). This decline in GC was also associated with a decrease in TFH cell differentiation and an increase in the number of TH1 cells (Kaneko et al., 2020). Further, an increase in expression of TNF-α levels was found in the follicles. Based on previous studies that TNF-α inhibits the lymphoid follicular development, and high levels of this pleiotropic cytokine is the hallmark of COVID-19, the authors attributed the reduction in GC to high levels of this cytokine. In addition to the study in post-mortem samples, the authors conducted B cell analysis in peripheral blood samples from COVID-19 patients at different stages of the disease. In line with the post-mortem data, patients with severe disease condition (n = 25) had a significant decrease in the number of naïve B cells, CD19+ B cells, and follicular B cell subsets in comparison to the healthy controls (n = 4), convalescent patients (n = 39), and moderate patients (n = 4). Thus, this study provides a probable cause for the B cell decline in severe cases of Covid-19. However, there was a significant difference in the mean age of severe patients (higher between 58 and 60) than the control, convalescent, and moderate group (30–45 years). Thus, the effect of age on the decline in B cells cannot be undermined in this study. More studies are needed to specifically look into the B cell number and activation status in COVID-19 patients concerning the disease severity to get a clear understanding of the role of these cells.