Taken together, these data demonstrate that severely affected COVID-19 patients have significant populations of circulating, SARS-CoV-2-experienced CD4+ T lymphocytes which are imprinted to express IL-21 and TGF-β, and thus qualify as instructors of B cell activation in continued, SARS-CoV-2-triggered immune reactions. The gene discussed is TGFB1; the disease is COVID-19.