Clinical effectiveness of medical ozone therapy in COVID-19: the evidence and gaps map.

Ozone therapy (OT), a medical procedure, has been showing good results during the coronavirus disease (COVID-19). We aimed to build an evidence and gaps map (EGM) of OT in the COVID-19 ranking the articles found according to levels of evidence and outcomes. The EGM brings bubbles of different sizes and different colors according to the articles. The OT intervention used was major or minor autohemotherapy, rectal insufflation and ozonized saline solution. EGM was based on 13 clinical studies using OT for COVID-19 involving a total of 271 patients. We found 30 outcomes related to OT in COVID-19. Our EGM divided the outcomes into six groups: 1-clinical improvement; 2-hospitalization; 3-inflammatory, thromboembolic, infectious, or metabolic markers; 4-radiological aspects, 5-viral infection and 6-adverse events. Major autohemotherapy was present in 19 outcomes, followed by rectal insufflation. Improvement in clinical symptoms of COVID-19, improvement of respiratory function, improvement of oxygen saturation, reduction in hospital internment, decrease in C-reactive protein, decrease in ferritin, decrease in lactate dehydrogenase, decrease in interleukin 6, decrease in D-dimer, radiological improvement of lung lesions and absence of reported adverse events were related in the papers. The most commonly used concentrations of OT in major autohemotherapy and in rectal insufflation were 40 µg/mL and 35 µg/mL, respectively. Here, we bring the first EGM showing the efficacy and safety of OT in the treatment of COVID-19. OT can be used as integrative medical therapy in COVID-19 at a low cost and improve the health conditions of the patients.

Ozone and growth factors in the treatment of arthralgias secondary to vaccination against Covid-19. Case report

Background: The use of vaccines as preventive agents for SARS-CoV-2 infection has generated collateral effects, including arthralgias. The objective of this case report was to describe the treatment and evolution of a patient with arthralgia secondary to vaccination with BNT162b2 (Pfizer - BioNTech), with ozone and ozonized growth factors. Methods: The patient was a 53-year-old, white male with no medical history who had received 2 doses of the BNT162b2 vaccine, with an interval of 6 weeks. After the second dose, the patient reported the permanence of arthralgia in the fifth finger of the right hand, and the third finger of the left hand with an intensity of 9-10 on the visual analog scale (VAS) scale. The patient was locally infiltrated with ozone 6 mg/mL (intra articular and with the glove technique), twice a week for 2 weeks, and was subsequently treated with platelet-derived growth factor, Silfradent (R) CGF (Concentrated Grow Factors) activated with ozone, in a single session. Results: The patient evolved satisfactorily with a final VAS reduction to a value of 1-2 and reduction of clinical symptoms. Medical ozone and regenerative medicine using CGF, can represent a useful complement in mitigating collateral effects such as post-vaccination arthralgias. Conclusions: Larger clinical studies are needed to demonstrate its clinical efficacy in this indication.

Ozone gas applied through nebulization as adjuvant treatment for lung respiratory diseases due to COVID-19 infections: a prospective randomized trial.

The objective of this study was to provide lung disinfection by nebulizing ozone gas with distilled water and olive oil for patients who have clinical symptoms due to coronavirus disease 2019 (COVID-19). The study attempted to reduce the viral load of COVID-19 in the lungs of patients, to provide a faster response to medical treatment. Between August 2020 and September 2020, 30 patients who met the study criteria were prospectively evaluated. There were 2 groups with 15 patients in each group: patients in control group were not treated with ozone and only received standard COVID-19 treatment; patients in ozone group received lung disinfection technique with ozone and standard COVID-19 treatment. A statistically significant difference was found in the length of stay in hospital, change in C-reactive protein, polymerase chain reaction results after 5 days, and computed tomography scores between two groups. There was no statistically significant difference in D-dimer, urea, lactate dehydrogenase, lymphocyte, leukocyte, and platelet between two groups. According to the data, we think that the lung disinfection technique applied with ozone inhalation reduces the rate of pneumonia in COVID-19 patients and makes the patients respond faster to the treatment and become negative according to the polymerase chain reaction tests. The study was approved by the Ethical Committee of the Istanbul Medipol University Clinical Trials (approval No. 0011) on July 2, 2020.

CORonavirus-19 mild to moderate pneumonia Management with blood Ozonization in patients with Respiratory failure (CORMOR) multicentric prospective randomized clinical trial.

BACKGROUND: Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia. METHODS: The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT). RESULTS: A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0-1] in the SoC arm vs. 2 [1-3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed. CONCLUSION: In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results.

Rationale for ozone-therapy as an adjuvant therapy in COVID-19: a narrative review.

Coronavirus disease 2019 (COVID-19) is the respiratory disease caused by the novel severe acute respiratory syndrome-coronavirus-2 and is characterized by clinical manifestations ranging from mild, flu-like symptoms to severe respiratory insufficiency and multi-organ failure. Patients with more severe symptoms may require intensive care treatments and face a high mortality risk. Also, thrombotic complications such as pulmonary embolisms and disseminated intravascular coagulation are frequent in these patients. Indeed, COVID-19 is characterized by an abnormal inflammatory response resembling a cytokine storm, which is associated to endothelial dysfunction and microvascular complications. To date, no specific treatments are available for COVID-19 and its life-threatening complication. Immunomodulatory drugs, such as hydroxychloroquine and interleukin-6 inhibitors, as well as antithrombotic drugs such as heparin and low molecular weight heparin, are currently being administered with some benefit. Ozone therapy consists in the administration of a mixture of ozone and oxygen, called medical ozone, which has been used for over a century as an unconventional medicine practice for several diseases. Medical ozone rationale in COVID-19 is the possibility of contrasting endothelial dysfunction, modulating the immune response and acting as a virustatic agent. Thus, medical ozone could help to decrease lung inflammation, slow down viral growth, regulate lung circulation and oxygenation and prevent microvascular thrombosis. Ozone-therapy could be considered a feasible, cost-effective and easy to administer adjuvant therapy while waiting for the synthesis of a therapy or the development of the vaccine.