As preexisting CD8+ T-cell responses have been associated with asymptomatic COVID-19 in individuals expressing HLA-B*15:01, comparing to mild disease, we defined cross-reactive CD8+ T-cells responses directed at the HLA-B*15:01/S919 epitope in COVID-19 patients across disease outcomes ranging from asymptomatic to critical illness. Here, HLA-B is linked to COVID-19.