The main findings can be summarized as follows: (i) reduced total lymphocyte count, CD4+ and CD8+ T cell count and CD4/CD8 ratio; and increased CD8+ HLA-DR MFI, and CD8+ NKG2A MFI on admission, were associated with progression to severe COVID-19; (ii) according to our logistic regression model, increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, including obesity and diabetes, is associated with a high risk of COVID-19 progression in these patients. This evidence concerns the gene CD8A and obesity due to melanocortin 4 receptor deficiency.