Compared with unvaccinated severely ill COVID-19 patients and unvaccinated patients with fatal COVID-19 outcomes, unvaccinated asymptomatic COVID-19 patients displayed significantly (i) higher rate of the α-CCC strain 229E (α-CCC-229E); (ii) higher frequencies of functional memory CD134+CD137+CD4+ and CD134+CD137+CD8+ T cells directed toward cross-reactive α-CCCs/SARS-CoV-2 epitopes from structural, non-structural, and regulatory proteins; and (iii) lower frequencies of cross-reactive exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells. The gene discussed is TIGIT; the disease is COVID-19.