Using peptide-HLA-I tetramers, we performed direct ex vivo tetramer enrichment to define the frequency and activation profiles of the responding SARS-CoV-2−specific CD8+ T cells in acute and convalescent COVID-19 patients and in prepandemic peripheral blood monocular cells (PBMCs), tonsil, and lung tissues from uninfected donors. The gene discussed is CD8A; the disease is COVID-19.