It is not clear to what extent their counterbalanced activities are mutually exclusive in homeostasis, but it has been suggested that an activity imbalance progresses COVID-19-related disease and the renin angiotensin aldosterone pathway.28 There have been extensive studies of ACE2 in COVID-19 (where the COVID-19 virus was found to engage ACE2 for cellular entry), including the identification of the upregulation of ACE2 with smoking34,35 and alcohol.36–38. This evidence concerns the gene ACE2 and COVID-19.