1) Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease in China at the end of 2019 has caused a large global outbreak. Systemic ozone therapy (OT) could be potentially useful in the clinical management of several complications secondary to SARS-CoV-2. The rationale and mechanism of action has already been proven clinically in other viral infections and has been shown in research studies to be highly effective at decreasing organ damage mediated by inflammation and oxidative stress. This review summarizes the OT studies that illustrate the possible cytoprotective mechanism of action of ozone and its physiological by-products in target organs affected by SARS-CoV-2. (2) Methods: This review encompasses a total of 74 peer-reviewed original articles. It is mainly focused on ozone as a modulator of the NF-κB/Nrf2 pathways and IL-6/IL-1β expression. (3) Results: In experimental models and the few existent clinical studies, homeostasis of the free radical and antioxidant balance by OT was associated with a modulation of NF-κB/Nrf2 balance and IL-6 and IL-1β expression. These molecular mechanisms support the cytoprotective effects of OT against tissue damage present in many inflammatory diseases, including viral infections. (4) Conclusions: The potential cytoprotective role of OT in the management of organ damage induced by COVID-19 merits further research. Controlled clinical trials are needed.
Currently, there is no effective antiviral therapy recommended for the new coronavirus disease 2019 pneumonia (COVID-19). The purpose of this study was to evaluate the safety and efficacy of Ozonized Saline Solution (O3SS) used as a complementary therapy in adult patients with mild to severe COVID-19. Twenty-five adult patients who were hospitalized with mild to severe COVID-19 symptoms, who met the inclusion criteria and were being treated from April 3rd to April 26th, 2020, at the Viamed Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were allocated to receive standard care (SC) that included 200-400 mg hydroxychloroquine twice daily for 5-7 days plus Tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin (LMWH) and 40 mg-60 mg metil-prednisone plus O3SS, 200 mL, 3-5 µg/mL daily for 10 days. Primary outcomes of treatment with O3SS were an improvement of clinical symptoms and a reduction in mortality. Secondary end points evaluated included participant clinical status, laboratory examinations, and duration of viral shedding. None of the patients treated with SC + O3SS died. Improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded with an improvement of laboratory finding including D-dimer, fibrinogen, LDH, and CRP. No side effects from the O3SS treatment were observed. Conclusions: COVID-19 patients with mild to severe symptoms who received intravenous O3SS as a complementary therapy demonstrated improved clinical symptoms, improved laboratory values and a reduction in mortality.
Context: Currently, there is no effective antiviral therapy recommended for novel coronavirus pneumonia 2019 (COVID-19). Aims: To assess the safety of ozonized saline solution (O3SS) used as a complementary therapy in adult COVID-19 patients. Methods: Twenty-five adult patients hospitalized with mild to severe symptoms of COVID-19, who met the inclusion criteria and were treated from April 18 to April 26, 2020, at Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were assigned to receive standard care consisting ceftriaxone (250 mg – 2 g twice daily for 7 days) plus azithromycin (500 mg once daily for 5 days), of 200 – 400 mg hydroxychloroquine twice daily for 5-7 days plus tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin and 40 to 60 mg metil-prednisone plus O3SS, 200 mL, 3-5 µg/mL per day for 10 days. No control group was included, the data was compared to clinical trials in this subject. Secondary endpoints assessed included the clinical status of participants, laboratory examinations, and duration of viral shedding. Results: Patients with COVID-19 with mild to severe symptoms who received intravenous O3SS as an adjunct treatment experienced no side effects. The main results of O3SS treatment were a tendency to improve clinical symptoms without side effects. None of the patients treated died. Conclusions: Early evidence of efficacy shown improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded to improvements in laboratory results including D-dimer, fibrinogen, lactate dehydrogenase, and C-reactive protein. These preliminary data will serve as the basis for a future study of the effectiveness of this therapy.
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