COVID-19 is the disease caused by the new coronavirus SARS-CoV-2 and is characterized by clinical manifestations ranging from mild, flu-like symptoms, to severe respiratory failure and multi-organ failure. Patients with more severe symptoms may require intensive care treatments and face a high risk of mortality. COVID 19 is characterized by an abnormal inflammatory response similar to a cytokine storm, which is associated with endothelial dysfunction and microvascular complications. To date, no specific treatments are available for COVID-19 and its potentially life-threatening complications. Numerous experimental and clinical observations have suggested that the gut microbiota plays a key role in sepsis and ARDS pathogenesis. The incidence of diarrhea in COVID-19 patients and the high mortality rate in elderly patients, considered together, indicate a possible involvement of the intestine-lung axis in COVID-19 with association of dysbiosis. Ozonetherapy is the administration of a mixture of ozone and oxygen, or Medical Ozone (MO), which produces a series of benefits capable of counteracting a wide range of pathologies, in use for over a century as an unconventional medicine practice. MO is fundamental to inhibit the activation of the inflammatory reaction and to obtain an antioxidant activity both in the tissue and in the blood. Oxidative ozone preconditioning causes an increase in SOD, GSH-Px values. MO, using large auto-hemo-infusion or rectal insufflation technique or ozonized water, could help oxygenate the tissues better, decrease gut inflammation and regulate immune response, help slow down viral growth, regulate circulation and avoid or slow down vascular hypertrophy and consequent hyperemia , especially in the early stages, with obvious benefit at microbiome level.