In contrast, a lower magnitude of CCCs/SARS-CoV-2 cross-reactive CD4+ T-cell responses were detected in unvaccinated severely ill COVID-19 patients and to patients with fatal COVID-19 outcomes and (ii) suggest a crucial role of CCCs/SARS-CoV-2 cross-reactive CD4+ T cells, directed towards structural, non-structural, and accessory protein antigens, in protection from symptomatic and fatal Infections in unvaccinated COVID-19 patients. The gene discussed is CD4; the disease is infection.