Insights on the mechanisms of action of ozone in the medical therapy against COVID-19

•Ozone is widely used in treating COVID-19 with encouraging results.•Ozone ability in tuning the Nrf2/Keap1/AE system leads to anti-inflammation.•Ozone can modulate the complex NO-mediated action on endothelia.•Ozone can regulate the thrombotic/anti-thrombotic mechanism in COVID-19.•Ozone is a possible new tool in dampening SARS-CoV2 pandemic. An increasing amount of reports in the literature is showing that medical ozone (O3) is used, with encouraging results, in treating COVID-19 patients, optimizing pain and symptoms relief, respiratory parameters, inflammatory and coagulation markers and the overall health status, so reducing significantly how much time patients underwent hospitalization and intensive care. To date, aside from mechanisms taking into account the ability of O3 to activate a rapid oxidative stress response, by up-regulating antioxidant and scavenging enzymes, no sound hypothesis was addressed to attempt a synopsis of how O3 should act on COVID-19. The knowledge on how O3 works on inflammation and thrombosis mechanisms is of the utmost importance to make physicians endowed with new guns against SARS-CoV2 pandemic. This review tries to address this issue, so to expand the debate in the scientific community.