The key objective of this review is to summarize the available information on the effects of medical ozone therapy in COVID-19 and its therapeutic potentials. An electronic literature search was performed using the PubMed, Cochrane, Web of Science, Science Direct, Scopus, Google Scholar, Ovid Medline, J Stage and China Knowledge Resource Integrated (CNKI) databases to September 2021. In total, 1833 articles were identified. Twenty-six articles were selected out of 667 articles. The most preferred and effective administration method for COVID-19 is major autohemotherapy (MAHT), followed by rectal insufflation and minor autohemotherapy (MiAHT). However, other methods, including ozonized oils and ozonated saline, are also used for COVID-19 due to ease of application, prophylactic and therapeutic effects. In studies, 850 patients were treated with ozone therapy as a complementary treatment. The effectiveness of ozone concentrations below 20 mu g/mL or above 45 mu g/mL for MAHT are yet to be proven in the COVID-19 patient population, and may be less effective. Complementary ozone therapy combined with antivirals increase the activity of antivirals against COVID-19. Large-scale, multicenter randomized clinical trials are needed to be able to isolate the effect of ozone therapy where the clinical variables are distributed more homogeneously. Also, an extended period of follow-up of COVID-19 patients may give more accurate indications about the effectiveness of the treatment in the long term.
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