The degree of extrafollicular B cell activation is characterized by an increase in CD11c+ activated naive (aN) B-cells which are precursors to IgD-CD27-, C-X-C chemokine receptor type 5 (CXCR5)-CD21- [double-negative 2 (DN2)] B-cells in addition to more recently discovered Cd11-CD21- (DN3) B-cell populations in severe COVID-19, which correlates with an increase in antibody-secreting cell populations (181) (Figure 2D). This evidence concerns the gene CR2 and COVID-19.