Figure 3. In vitro–stimulated B cells from a representative disease control, a patient with mild COVID-19, and a patient with severe COVID-19 show different patterns of clonal IgG cross-reactivity to human coronavirus strains.

B cells were isolated from peripheral blood samples and stimulated in vitro in oligoclonal cultures at limiting dilution to analyze IgG reactivity at the clonal level. The representative patients were analyzed on the indicated day or week after the onset of symptoms. (A) Heatmaps show the MFI of clonal IgG reactivity to N of different human coronaviruses. The number of single- and cross-reactive N-specific B cell clones (x axis) remained stable in the disease control (green) but increased over time after SARS-CoV-2 infection in the patients with mild (blue) or severe (red) COVID-19. (B) Heatmaps show the MFI of clonal IgG reactivity to S_ECTO, S₁, and S_RBD antigens from the same representative patients. The disease control showed stable reactivity. By contrast, the patient with severe COVID-19 showed the strongest response to OC43-S_ECTO, and this response poorly cross-reacted with SARS-CoV-2 antigens.