However, although the majority of clinical studies supports the safety of RAAS blockers treatment in COVID-19 patients [65–67], a recent randomized clinical trial in critically ill patients with COVID-19 showed that initiating treatment with an ACE inhibitor or an angiotensin receptor blocker during hospitalization did not improve, and likely worsened, clinical outcomes [20], but no mechanistic hypothesis was advanced. This evidence concerns the gene ACE and COVID-19.