Objective This study evaluated the potential efficacy of a novel approach to treat COVID-19 patients, using an oxygen-ozone (O 2 -O 3 ) mixture, via a process called Oxygen-Ozone- Immunoceutical Therapy. The methodology met the criteria of a novel, promising approach to treat successfully elderly COVID-19 patients, particularly when hospitalized in intensive care units (ICUs) Experimental design : We investigated the therapeutic effect of 4 cycles of O 2 -O 3 in 50 hospitalized COVID-19 subjects suffering from acute respiratory disease syndrome (ARDS), aged more than 60 years, all males and undergoing non invasive mechanical ventilation in ICUs. Results Following O 2 -O 3 treatment a significant improvement in inflammation and oxygenation indexes occurred rapidly and within the first 9 days after the treatment, despite the expected 14–20 days. A significant reduction of inflammatory and thromboembolic markers (CRP, IL-6, D-dimer) was observed. Furthermore, amelioration in the major respiratory indexes, such as respiratory and gas exchange markers (SatO 2 %, PaO 2 /FiO 2 ratio), was reported. Conclusion Our results show that O 2 -O 3 treatment would be a promising therapy for COVID-19 patients. It leads patients to a fast recovery from ARDS via the improvement of major respiratory indexes and blood gas parameters, following a relatively short time of dispensed forced ventilation (about one to two weeks). This study may encourage the scientific community to further investigate and evaluate the proposed method for the treatment of COVID-19 patients.

An increasing amount of reports in the literature is showing that medical ozone (O 3 ) 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 O 3 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 O 3 should act on COVID-19. The knowledge on how O 3 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.

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy (NIRS) system to monitor the cerebral metabolism and a transcranial Doppler (TCD) to monitor the blood flow velocity in the middle cerebral arteries. Fifty-four subjects (32 neurological patients and 22 controls) were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). As a primary endpoint of the work, we showed the changes in the brain metabolism and circulation of the entire population. The concentration of oxygenated haemoglobin increased after the reinjection of the ozoned blood and remained higher than the beginning for another 1.5 hours. The concentration of the deoxygenated haemoglobin decreased during the therapy and the CYT-c concentration markedly increased about 1 hour after the reinjection. No significant changes were observed on the blood flow velocity. As secondary endpoint, we compared the NIRS metabolic pattern of 20 remitting-relapsing multiple sclerosis (MS) patients against 20 controls. We showed that by using only 7 NIRS variables it was possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long-term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

After several years of scientific research and accurate clinical practice, the oxygen-ozone therapy continues to represent a method full of prospects and new opportunities. On this basis we present an updated review on basic mechanisms through which the ozone acts. Ozone, a molecule notable for its heterodoxy and atypicalness, has been regarded with suspicious for a long time since it was a possible generator of free radicals and correlated pathologies, but it is important distinguishing between the oxidative damage from free radicals, characterized by irreversible chemical modifications of the molecular target, and the physiological effects from free radicals (redox signaling), characterized on the other hand, by reversible chemical and selective alterations, which are potentially suitable to become an active part in the various metabolic regulation mechanisms, with positive effects on several pathologies.

The problems related to the approach to the outbreak of COVID-19 in the world require that all possible effective treatment options be explored. The clinical criterion of the researcher is not to refuse a priori, but to verify and evaluate the proposals that are made. Italian Society of Oxygen Ozone Therapy (SIOOT) proposed to the Italian ISS (Italian Institute of Health) to use oxygen ozone therapy (O2O3) in patients with COVID-19. (...)