Abnormal ACE2 expression, angiotensin II and angiotensin 1–7 imbalance, and TMPRSS2 androgen-mediated overactivity seem to be key regulators of SARS-CoV-2 infectivity, in accordance with epidemiological observations of hypertension, obesity, and male sex as being major risk factors. This evidence concerns the gene TMPRSS2 and obesity due to melanocortin 4 receptor deficiency.