In agreement with our previous findings based on acute virus infection models in mice (29, 36), our clinical study suggests that a checkpoint therapy might enhance the functionality of the PD-1-expressing cytotoxic CD8+ T cells in COVID-19 patients and improve virus control, but with a potential to exaggerate the immunopathology in the lung and other organs, which might actually accelerate decompensation. This evidence concerns the gene CD8A and COVID-19.