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

ABSTRACT: 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.

SUBMITTER: Ranaldi GT

PROVIDER: S-EPMC8086623 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionUsing ozone therapy to manage COVID-19 patients has been accompanied by conflicting results in prior studies. Therefore, we aimed to widely assess the effects of ozone as adjuvant therapy in COVID-19 patients.MethodsPubMed, Scopus, Web of Science, Cochrane, ProQuest, Springer, and Sage journals were searched systematically until April 2022. Mortality rate, ICU admission, hospital-length stay, negative PCR, pulmonary, renal, and hepatic functions, as well as inflammatory and blood systems were pooled to compare the efficacy of ozone as adjacent therapy (OZ) and standard treatment (ST). Analyses were run with the random/fixed models, sub-group analysis, funnel plot, and sensitivity analysis using comprehensive meta-analysis (CMA) software version 2.0.ResultsThe results of four randomized clinical trials (RCTs) and four case-control studies with a total of 371 COVID-19 positive patients were analyzed. The OZ group patients had a shorter length of hospital stay (P > 0.05), lower ICU admissions (P > 0.05), and lower mortality rates (P < 0.05) than the ST group cases. After treatment, 41% more COVID-19 patients had negative PCR tests than the ST group (P < 0.05). Serum creatinine and urea levels were not modified in either group (P > 0.05). Moreover, except for albumin serum levels, which decreased significantly in the OZ group, serum bilirubin, ALT, and AST were not modified in either group (P > 0.05). Both arms did not show a decrease in C-reactive protein blood levels (P > 0.05), but the OZ group showed a significant modification in LDH serum levels (P < 0.05). Unlike the d-dimer and WBC serum levels (P > 0.05), platelet levels were increased in the OZ group (P < 0.05). No negative side effects were demonstrated in either group.ConclusionOzone therapy was effective significantly on PCR test and LDH serum levels, as well as mortality based on overall estimation. Concerning the length of hospital stay and ICU admissions, although the results were insignificant, their effect sizes were notable clinically. More RCT studies are needed to show the efficacy of ozone therapy on other studied variables.

Project description:Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of Pneumocystis jirovecii pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to Fusarium spp., and 1 case of pulmonary infection due to Scedosporium.

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

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