The Mito-Hormetic Mechanisms of Ozone in the Clearance of SARS-CoV2 and in the COVID-19 Therapy

Abstract

An increasing body of evidence in the literature is reporting the feasibility of using medical ozone as a possible alternative and adjuvant treatment for COVID-19 patients, significantly reducing hospitalization time, pro-inflammatory indicators, and coagulation markers and improving blood oxygenation parameters. In addition to the well-described ability of medical ozone in counteracting oxidative stress through the upregulation of the main anti-oxidant and scavenging enzymes, oxygen–ozone (O2–O3) therapy has also proved effective in reducing chronic inflammation and the occurrence of immune thrombosis, two key players involved in COVID-19 exacerbation and severity. As chronic inflammation and oxidative stress are also reported to be among the main drivers of the long sequelae of SARS-CoV2 infection, a rising number of studies is investigating the potential of O2–O3 therapy to reduce and/or prevent the wide range of post-COVID (or PASC)-related disorders. This narrative review aims to describe the molecular mechanisms through which medical ozone acts, to summarize the clinical evidence on the use of O2–O3 therapy as an alternative and adjuvant COVID-19 treatment, and to discuss the emerging potential of this approach in the context of PASC symptoms, thus offering new insights into effective and safe nonantiviral therapies for the fighting of this devastating pandemic.

Comments on the optimal use of medical ozone in clinics versus the Ozone High Dose Therapy (OHT) approach

“…The authors used a complessive amount of 14,000 μg O 3 (14 mg O 3 ) for each single pass, about 1.55–1.75 times the dosage usually employed by O 2 -O 3 -MAHT and recommended by the International Scientific Society of Oxygen Ozone Therapy (SIOOT) particularly in COVID-19 [ 17 , 18 ]. The complessive amount of O 3 in the SIOOT-recommended O 2 -O 3 -MAHT does nor exceed 40,000 ppm, disposed into a maximum of four sessions [ 18 , 19 ], whereas OHT uses an amount of O 3 more than three times higher [ 1 ].…”

Ozone in the adjunct medical treatment. The round personality of a molecule with hormetic properties

“…57,58 If low doses (hormetic) ozone, via its metabolites, such as 4-HNE, has an anti-inflammatory potential, it exerts also a reduction in painful symptomatology, including other discomforts such as fatigue, as occurring in some debilitating chronic diseases, including post-COVID. 59,60 Furthermore, medical ozone at low doses, by activating the Nrf2-mediated antioxidant system, may exert a fundamental role on the reduction of neuropathic pain, probably by increasing the levels of glutathione, which in turn inhibits NF-κB activation. 61,62 Just in COVID-19, the adjunct medical treatment with ozone reported several encouraging results, particularly from SIOOT, 59,[63][64][65][66] inasmuch ozone, in the dose range 30-45 μg/mL, showed the ability to recover the O 2 saturation % indexes and inhibit the increase of inflammatory biomarkers.…”

“…59,60 Furthermore, medical ozone at low doses, by activating the Nrf2-mediated antioxidant system, may exert a fundamental role on the reduction of neuropathic pain, probably by increasing the levels of glutathione, which in turn inhibits NF-κB activation. 61,62 Just in COVID-19, the adjunct medical treatment with ozone reported several encouraging results, particularly from SIOOT, 59,[63][64][65][66] inasmuch ozone, in the dose range 30-45 μg/mL, showed the ability to recover the O 2 saturation % indexes and inhibit the increase of inflammatory biomarkers. 63 The anti-oxidant potential of low doses of ozone, which activate ROS-mediated signaling, 36 is preludial to the antiinflammatory and immune-modulatory role of ozone treatment.…”

“…If low doses (hormetic) ozone, via its metabolites, such as 4-HNE, has an anti-inflammatory potential, it exerts also a reduction in painful symptomatology, including other discomforts such as fatigue, as occurring in some debilitating chronic diseases, including post-COVID. 59,60 Furthermore, medical ozone at low doses, by activating the Nrf2-mediated antioxidant system, may exert a fundamental role on the reduction of neuropathic pain, probably by increasing the levels of glutathione, which in turn inhibits NF-κB activation. 61,62…”

“…Just in COVID-19, the adjunct medical treatment with ozone reported several encouraging results, particularly from SIOOT, 59,63–66 inasmuch ozone, in the dose range 30-45 μg/mL, showed the ability to recover the O 2 saturation % indexes and inhibit the increase of inflammatory biomarkers. 63…”