Abstract
(1) Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) 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.
Highlights
Coronaviruses are important human and animal pathogens
Some in vitro or in vivo studies suggest potential therapeutic activity of compounds against related coronaviruses, but there are no available data from observational studies or randomized controlled trials in humans to support recommending any investigational therapeutics for patients with confirmed or suspected COVID-19 at this time
This implies that the cytoprotective effect observed during the O2 /O3 treatment may impact clinical conditions caused by SARS-CoV-2
Summary
Coronaviruses are important human and animal pathogens. At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan (Hubei Province of China) and caused a large global outbreak representing a major public health issue [1]. Some in vitro or in vivo studies suggest potential therapeutic activity of compounds against related coronaviruses, but there are no available data from observational studies or randomized controlled trials in humans to support recommending any investigational therapeutics for patients with confirmed or suspected COVID-19 at this time. The main mechanism of O2 /O3 on human physiology fits the concept of oxidative preconditioning [17] This concept has been demonstrated at both the proteomic and genomic level [18], in in vitro studies and in clinical trials [19]. The modulation of O2 /O3 at the Keap1/Nrf2/ARE pathway and the reduction of IL-6 and IL-1β are involved in the mechanism of action of ozone [21] This implies that the cytoprotective effect observed during the O2 /O3 treatment may impact clinical conditions caused by SARS-CoV-2. The exclusion criteria were the lack of free access to complete text due to financial constraints and/or, studies presenting inadequate scientific evidence
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