In summary, the demonstration that overexpression of attached ACE2 compared to circulating, aberrancies in ACE2 expression and activity, predominant pro-inflammatory angiotensin II-AT1 over angiotensin 1–7-Mas receptor axis, and increased TMPRSS2 expression as keys to determine COVID-19 severity [48–53] allows the hypothesis that regulation of endocrine system may be central for improvement of COVID-19 related outcomes in clinical practice. The gene discussed is TMPRSS2; the disease is COVID-19.