CD4 and COVID-19: We found a significant decrease in the frequencies of CD4+ T cells specific to all the five highly conserved CCCs/SARS-CoV-2 cross-reactive DRB1*01:01-restricted epitopes in the three groups of unvaccinated severely ill COVID-19 and unvaccinated COVID-19 patients with fatal outcomes (i.e., patients with severity 3, 4, and 5) compared to the remaining three groups of unvaccinated COVID-19 patients with low to no severe disease (i.e., patients with severity 1, 2—p ≤ 0.01) and to unvaccinated asymptomatic COVID-19 patients (severity 0—p ≤ 0.002) (Figure 4A).