CTLA4 and COVID-19: Similarly, there were significantly higher frequencies of phenotypically exhausted CD8+ T cells in unvaccinated severely ill COVID-19 and patients with fatal outcomes compared to unvaccinated asymptomatic COVID-19 patients (Figure 6A—up to ∼3.6-fold increase for S1220–1228-specific PD-1+TIGIT+CD8+ T cells and up to ∼4.6-fold increase for S1220–1228- and ORF103-11-specific TIM-3+CTLA-4+CD8+ T cells).