Is Ozone therapy an adjunct treatment for SARS-CoV-2 / COVID-19 infection?

Abstract Up to today, there is no specific treatment against SARS-CoV-2 / COVID-19 infection; there the necessity to search for alternatives that help patients with COVID-19. The objective of this study was to review the use of ozone therapy as adjunct treatment for SARS-CoV-2 / COVID-19 infection, highlighting the mechanisms of action, forms of application and current clinical evidence. A systematic review was conducted in electronic databases, searching the terminology Ozone "or" Ozone therapy "and" SARS-CoV-2 or COVID-19 or Coronavirus. Results: nineteen studies were included; ten were editorials, comments, brief reports or reviews, and nine clinical studies. We found that ozone therapy could be favorable for treating patients infected with SARS-CoV-2 / COVID-19, through a direct antiviral effect, regulation of oxidative stress, immunomodulation and improvement of oxygen metabolism. Patients who were treated with ozone therapy responded favorably; therefore, ozone therapy appears to be a promising treatment for patients infected with SARS-CoV-2 / COVID-19. Its mechanism of action justifies its use as an adjuvant therapy; however, scientific evidence is based on case series and clinical trials are necessary to corroborate its effectiveness and safety.

Evaluating the Effectiveness of Intravenous Ozonated Normal Saline in the Treatment of Severe COVID-19 Disease: A randomized control trial

Background: There is still no specific treatment strategy for COVID-19 other than supportive management. The potential biological benefits of ozone therapy include reduced tissue hypoxia, decreased hypercoagulability, modulated immune function by inhibiting inflammatory mediators, improved phagocytic function, and impaired viral replication. This study aimed to evaluate the effect of intravenous ozonated normal saline on patients with severe COVID-19 disease. Method(s): In this study, a single centralized randomized clinical trial was conducted on 80 hospitalized patients with severe COVID-19. The patients were selected by random allocation method and divided into two groups A and B. In group A (control group), patients were given standard drug treatment, and in group B (intervention group), patients received ozonated normal saline in addition to the standard drug treatment. In the intervention group, 400 mL of normal saline was weighed by 40 mug/ kg of body weight and was injected into patients within 15 to 30 minutes (80 to 120 drops per minute). This process was done daily every morning for a week. Primary and secondary outcomes of the disease included changes in the following items: length of hospital stay, inflammatory markers including C-reactive protein (CRP), clinical recovery, arterial blood oxygen status, improvement of blood disorders such as leukopenia and leukocytosis, duration of ventilator attachment, and rapid clearance of lung lesions on CT scans. The need for intensive care unit (ICU) hospitalization, the length of ICU stay, and the mortality rate in patients of the two groups was compared. Result(s): According to the results of the initial outcome variable analysis, the probability of discharge of patients who received the normal ozonated saline intervention was 33% higher than patients who did not receive this intervention;however, this relationship was not statistically significant (HR = 0.67, 95%, CI = 0.42-1.06, P value = 0.089). The chance of ICU hospitalization in patients of the intervention group was three times more than that of the comparison group, but this relationship was not significant (odds ratio = 4.4 95% CI = 1.32-14.50, P value = 0.016). The use of ozonated normal saline was found to increase the risk of death by 1.5 times but this relationship was not statistically significant (odds ratio = 1.5, 95% CI = .24-9.75, P value = 0.646). Ozonated normal saline had a significant effect on changes in respiration rate (in the intervention group the number of breaths was decreased) and the erythrocyte sedimentation rate (in the intervention group the erythrocyte sedimentation rate was increased);however, it had no significant effect on other indicators. Conclusion(s): The present study showed that ozone therapy in hospitalized patients with severe COVID-19 could help improve some primary and secondary outcomes of the disease. Governments and health policymakers should make ozone therapy an available care service so that the need for advanced treatment facilities decreases;consequently, this measure may improve patient safety, prevent lung tissue destruction, and control cytokine storms in patients. Additionally, health decision-makers need to aim for the effective clinical improvement of patients, especially severe ones, and the reduction of their mortality. However, further large-scale multicenter studies with larger sample sizes considering drug side effects and other variables influencing the clinical course of COVID-19 can provide more information on the effectiveness and importance of ozone therapy.Copyright © 2023 The Author(s);Published by Kerman University of Medical Sciences.

Evaluation of the Potential Impact of Medical Ozone Therapy on Covid-19: A Review Study

The key objective of this review is to summarize the available information on the effects of medical ozone therapy in COVID-19 and its therapeutic potentials. An electronic literature search was performed using the PubMed, Cochrane, Web of Science, Science Direct, Scopus, Google Scholar, Ovid Medline, J Stage and China Knowledge Resource Integrated (CNKI) databases to September 2021. In total, 1833 articles were identified. Twenty-six articles were selected out of 667 articles. The most preferred and effective administration method for COVID-19 is major autohemotherapy (MAHT), followed by rectal insufflation and minor autohemotherapy (MiAHT). However, other methods, including ozonized oils and ozonated saline, are also used for COVID-19 due to ease of application, prophylactic and therapeutic effects. In studies, 850 patients were treated with ozone therapy as a complementary treatment. The effectiveness of ozone concentrations below 20 μg/mL or above 45 μg/mL for MAHT are yet to be proven in the COVID-19 patient population, and may be less effective. Complementary ozone therapy combined with antivirals increase the activity of antivirals against COVID-19. Large-scale, multicenter randomized clinical trials are needed to be able to isolate the effect of ozone therapy where the clinical variables are distributed more homogeneously. Also, an extended period of follow-up of COVID-19 patients may give more accurate indications about the effectiveness of the treatment in the long term. [ FROM AUTHOR] Copyright of Ozone: Science & Engineering is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Oxidation and "Unconventional” Approaches to Infection

Nonpharmacological approaches can be useful to control infectious diseases. Historically infection has been successfully managed with oxidation therapy methods that support the body's own innate defenses. Several modalities include ozone and hyperbaric oxygen therapy, ultraviolet blood irradiation (UBI), intravenous hydrogen peroxide, and ascorbate therapies. Oxidation therapies are virtually 100% safe, and repeatedly reported as highly and quickly effective in quelling infection (bacterial and viral) either as stand-alone therapies or adjunctive with drugs. They are directly and indirectly germicidal, and modulate the immune system via pro-oxidant signaling molecules. Oxidation therapies especially enhance oxygen delivery and metabolism, critical for all infection defenses. Ozone has remitted Ebola, COVID-19, and bacterial infections. UBI defeated most preantibiotic era infections in hospitals. Not being drug therapy, the effects of oxidation defenses, used by planetary animal life for millions of years, are not diminished by antibiotic-resistant organisms. Oxidation, depending on delivery method, can be very inexpensive and third world adaptable. This chapter summarizes the use of these key modalities, by exploring known published literature. © 2022 Elsevier Inc. All rights reserved.

The possibilities of using the effects of ozone therapy in neurology

OBJECTIVES: The beneficial effects of ozone therapy consist mainly of the promotion of blood circulation: peripheral and central ischemia, immunomodulatory effect, energy boost, regenerative and reparative properties, and correction of chronic oxidative stress. Ozone therapy increases interest in new neuroprotective strategies that may represent therapeutic targets for minimizing the effects of oxidative stress. METHOD(S): The overview examines the latest literature in neurological pathologies treated with ozone therapy as well as our own experience with ozone therapy. The effectiveness of treatments is connected to the ability of ozone therapy to reactivate the antioxidant system to address oxidative stress for chronic neurodegenerative diseases, strokes, and other pathologies. Application options include large and small autohemotherapy, intramuscular application, intra-articular, intradiscal, paravertebral and epidural, non-invasive rectal, transdermal, mucosal, or ozonated oils and ointments. The combination of different types of ozone therapy stimulates the benefits of the effects of ozone. RESULT(S): Clinical studies on O2-O3 therapy have been shown to be efficient in the treatment of neurological degenerative disorders, multiple sclerosis, cardiovascular, peripheral vascular, orthopedic, gastrointestinal and genitourinary pathologies, fibromyalgia, skin diseases/wound healing, diabetes/ulcers, infectious diseases, and lung diseases, including the pandemic disease caused by the COVID-19 coronavirus. CONCLUSION(S): Ozone therapy is a relatively fast administration of ozone gas. When the correct dose is administered, no side effects occur. Further clinical and experimental studies will be needed to determine the optimal administration schedule and to evaluate the combination of ozone therapy with other therapies to increase the effectiveness of treatment.Copyright © 2021 Neuroendocrinology Letters.

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.

The role of ozone therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19): a review.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has rapidly swept across the world. As new knowledge regarding treatment options for COVID-19 has emerged, the use of ozone therapy in the context of SARS-CoV-2 infection as an integrative therapeutic option supplementary to standard treatment regimen has been assessed in the present literature. We reviewed, critically analyzed, and summarized all present published literature on ozone therapy in association with COVID-19 via the PubMed database. Various reports and studies on the use of ozone (major autohemotherapy, rectal ozone insufflation, ozone inhalation) in patients affected by COVID-19 indicate that ozone therapy may reduce morbidity and accelerate recovery, while exhibiting a high safety profile with no relevant adverse effects. Current literature suggests that integrating ozone therapy into the existing standard of care and best available therapy for the treatment of COVID-19 patients offers major advantages in terms of superior clinical outcome parameters and amelioration of laboratory results. Further prospective studies are warranted to guide the next steps in the clinical application of ozone therapy and examine its impact on the course of COVID-19.

Efficacy of ozone adjuvant therapy in COVID-19 patients: A meta-analysis study.

Introduction: Using 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. Methods: PubMed, 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. Results: The 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. Conclusion: Ozone 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.

Internet of Medical Things - The Future of Healthcare

Background: The Internet of Medical Things (IoMT) is now being connected to medical equipment to make patients more comfortable, offer better and more affordable health care options, and make it easier for people to get good care in the comfort of their own homes. Objective(s): The primary purpose of this study is to highlight the architecture and use of IoMT (Internet of Medical Things) technology in the healthcare system. Method(s): Several sources were used to acquire the material, including review articles published in various journals that had keywords such as, Internet of Medical Things, Wireless Fidelity, Remote Healthcare Monitoring (RHM), Point-of-care testing (POCT), and Sensors. Result(s): IoMT has succeeded in lowering both the cost of digital healthcare systems and the amount of energy they use. Sensors are used to measure a wide range of things, from physiological to emotional responses. They can be used to predict illness before it happens. Conclusion(s): The term "Internet of Medical Things" refers to the broad adoption of healthcare solutions that may be provided in the home. Making such systems intelligent and efficient for timely prediction of important illnesses has the potential to save millions of lives while decreasing the burden on conventional healthcare institutions, such as hospitals. patients and physicians may now access real-time data due to advancements in IoM. Copyright © 2022 Wal et al.

SYSTEMIC OZONE THERAPY AND ITS IMMUNOMODULATORY EFFECTS IN COVID-19 PATIENTS

Objective: To evaluate the effect of systemic ozone therapy (OT) on the concentration of pro-inflammatory and anti-inflammatory cytokines in the blood in the complex treatment of COVID-19 patients. Material(s) and Method(s): The study included 65 patients with a confirmed diagnosis COVID-19 characterized by a moderate and severe course of the disease. The patients were admitted to the Infectious Disease Hospital of the V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. The patients' age ranged from 29 to 78 years. All patients were treated in accordance with the Temporary Guidelines of the Ministry of Health of Russia "Prevention, Diagnosis and Treatment of Coronavirus Infection (COVID-19)". Two groups of patients were randomly formed. The first group included 35 patients whose complex therapy included OT: intravenous administration of 400 ml of ozonated saline solution with an ozone concentration of 4 mg/L;a total course consisting of 6 procedures performed every other day. The second group included 30 patients who did not have OT. Clinical and laboratory parameters were evaluated on admission to the Infectious Disease Hospital and after two weeks of complex treatment;clinical, laboratory, special, statistical research methods were used. The content of cytokines GM-CSF, IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-8, IL-10 and their ratios were determined with a multiplex method on the Bioplex 200 analyzer (Bio-Rad, USA) using Bio-Plex Pro Human Cytokine 8-plex Panel (Bio-Rad, USA). Result(s): On admission to the Infectious Disease Hospital 47/65 (72,3%) patients had a moderate course of the disease and 18/65 (27.7%) patients had a severe one. The length of hospital stay in the group of patients with OT averaged 12.2 (2.7) (8-17) days, and it was 17.9 (4.2) (12-26) days in the group of patients who did not have OT. On admission, all patients had an increase in the level of C-reactive protein in their blood serum;the cytokine content in patients of the groups differed from the initial cytokine level and it was different between groups after two weeks of therapy. The medians of the pro-inflammatory cytokines IL-2, IL-6, IL-8 were particularly different. The content of these cytokines remained elevated in the second group of patients who did not have OT, compared with the baseline data and compared with the first group. The study of anti-inflammatory cytokines showed that the patients of the first group who had OT demonstrated a significantly higher IL-10 content compared to IL-10 content in the patients of the second group. Ratios of pro-and anti-inflammatory cytokines IL-2/IL-10, IL-2/ IL-4, IL-6/IL-10, IL-6/IL-4, IL-8/IL-10, IL-8/IL-4, TNF-alpha/IL-4 in the first group of patients with OT significantly decreased compared to the baseline indicator, which can be suggestive of a marked decrease in the activity of the inflammatory process. Conclusion(s): The positive effect of systemic OT on the clinical course of the disease has been revealed. Laboratory indicators in COVID-19 patients have shown a decrease in the severity of the inflammatory response. Besides having anti-inflammatory and immunomodulatory effect, OT helps to stop the process, improve the condition of patients and reduce the length of hospital stay. Systemic OT should be considered as an additional adjuvant method in the complex treatment of patients with SARS-CoV-2 infection. Copyright © A group of authors, 2022.

The Mito-Hormetic Mechanisms of Ozone in the Clearance of SARS-CoV2 and in the COVID-19 Therapy.

An increasing body of evidence in the literature is reporting the feasibility of using medical ozone as a possible alternative and adjuvant treatment for COVID-19 patients, significantly reducing hospitalization time, pro-inflammatory indicators, and coagulation markers and improving blood oxygenation parameters. In addition to the well-described ability of medical ozone in counteracting oxidative stress through the upregulation of the main anti-oxidant and scavenging enzymes, oxygen-ozone (O2-O3) therapy has also proved effective in reducing chronic inflammation and the occurrence of immune thrombosis, two key players involved in COVID-19 exacerbation and severity. As chronic inflammation and oxidative stress are also reported to be among the main drivers of the long sequelae of SARS-CoV2 infection, a rising number of studies is investigating the potential of O2-O3 therapy to reduce and/or prevent the wide range of post-COVID (or PASC)-related disorders. This narrative review aims to describe the molecular mechanisms through which medical ozone acts, to summarize the clinical evidence on the use of O2-O3 therapy as an alternative and adjuvant COVID-19 treatment, and to discuss the emerging potential of this approach in the context of PASC symptoms, thus offering new insights into effective and safe nonantiviral therapies for the fighting of this devastating pandemic.

Mechanisms of Action of Ozone Therapy in Emerging Viral Diseases: Immunomodulatory Effects and Therapeutic Advantages With Reference to SARS-CoV-2.

Medical oxygen-ozone (O2-O3) is a successful therapeutic approach accounting on the assessed beneficial action of ozone in the range 30-45 µg/ml (expanded range 10-80 µg/ml according to different protocols), as in this dosage range ozone is able to trigger a cellular hormetic response via the modulating activity of reactive oxygen species (ROS), as signaling molecules. The ozone-dependent ROS-mediated fatty acid oxidation leads to the formation of lipid ozonization products (LOPs), which act as signal transducers by triggering ROS signaling and therefore mitohormetic processes. These processes ultimately activate survival mechanisms at a cellular level, such as the Nrf2/Keap1/ARE system activation, the AMPK/FOXO/mTOR/Sir1 pathway and the Nrf2/NF-kB cross talk. Furthermore, indirectly, via these pathways, LOPs trigger the HIF-1α pathway, the HO-1 signaling and the NO/iNOS biochemical machinery. Ozone-driven shift of cytokine activation pathways, from pro-inflammatory to anti-inflammatory immediately afterwards, also exert direct immunoregulatory effects on regulatory T lymphocytes as well as on the intestinal microbiota, which in turn can affect immune response thus influencing the progression of the disease. In this review, we will describe the biological and biochemical mechanisms of action of ozone therapy with the aim of evaluating both positive and critical aspects of ozone use as a therapeutic adjuvant in the light of emerging viral infections, such as SARS-CoV-2 and microbiome-associated disorders related to SARS-CoV-2.

COVID-19 and low back pain: previous infections lengthen recovery time after intradiscal ozone therapy in patients with herniated lumbar disc.

PURPOSE: To assess and compare the clinical effectiveness of percutaneous intradiscal ozone therapy in patients affected by lumbar disc herniation, with and without history of COVID-19 infection. MATERIALS AND METHODS: After the rising of COVID-19 pandemics in Italy, 47 consecutive percutaneous intradiscal ozone therapies were performed on patients with low back pain and/or sciatic pain due to lumbar disc herniation. Among these, 19 had suffered from COVID-19 and successively recovered with no residual symptoms, while the remaining 28 had not previously been affected by COVID-19 and were not convalescent. Oswestry Disability Index (ODI) was administered before the treatment and at 1-month and 3-month follow-up in order to assess the clinical outcome. RESULTS: The two groups were similar in terms of patient age (p-value 0.54), treated levels (p-value 0.26) and pre-procedure ODI (p-value 0.33). Technical success was achieved in all cases. In patients previously affected by COVID-19, mean ODI decrease was 11.58 ± 9.51 (35.72%) at 1-month follow-up and 20.63 ± 9.87 (63.63%) at 3-month follow-up. In patients never affected by COVID-19, mean ODI decrease was 20.93 ± 10.53 (58.73%) at 1-month follow-up and 22.07 ± 11.36 (61.92%) at 3-month follow-up. Eventually, clinical success was registered in 84.21% (16/19) of patients with history of COVID-19 infection and in 85.71% (24/28) of patients with no history of COVID-19 infection. No major complication was registered. CONCLUSIONS: In case of lumbar disc herniation treated with percutaneous intradiscal ozone therapy, patients previously affected by COVID-19 showed a significantly longer recovery time.

MODERN APPLICATIONS OF OZONE FOR COVID-19 DISINFECTION AND TREATMENT

Coronavirus disease 2019 represents a serious challenge for modern society worldwide because of the considerable and unfavourable consequences of the pandemic in terms of human health, economics and social life. In the present concise survey, some essential peculiarities of ozone as disinfecting and therapeutic means under the conditions of COVID-19 pandemic as reflected in the recent literature are described. Particularttention is paid to modern hospital disinfection means and methods. Ozone exerts antiviral activity through the inhibition of viral replication and direct inactivation of viruses by interfering with the virus replication phase and attacking capsid proteins. Ozone therapy is very inexpensive and may safely exploit the critical vulnerability in COVID-19.

Applications of Artificial Intelligence for Rehabilitation of Post-Covid-19 Syndrome

Introduction: The aim of this research was to investigate the possible consequences of COVID-19 on musculoskeletal, nervous system and psychological experience. Methods: Recent research has shown that patients’ risks related to severe COVID-19 disease vary depending on age, underlying comorbidities, and medical history. We performed a detailed selection of papers describing post-COVID-19 syndrome, which affects musculoskeletal, nervous system, and psychological conditions. Results: We summarized a possible rehabilitation process using traditional rehabilitation, telerehabilitation, and virtual reality for rehabilitation using online programs that promote mental health. The use of a combined method of rehabilitation with ozone therapy brings about new perspectives for pre-pandemic prevention and post-pandemic treatment. Conclusion: We have shown the direction of further research: monitoring and evaluating post-COVID-19 syndrome patients using artificial intelligence to design their optimal rehabilitation. © 2021. All Rights Reserved.

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.

Using Ozone Therapy as an Option for Treatment of COVID-19 Patients: A Scoping Review.

Recent investigations are seeking a novel treatment to control the new pandemic of coronavirus 19 (COVID-19). The aim of this systematic review was to study the effect of ozone therapy on COVID-19 patients and the available supporting evidence. Electronic databases including MEDLINE (via PubMed), EMBASE, Cochrane Library (CENTRAL), and TRIP, clinical trial registries, and preprint sources were searched for published evidence-based articles. In addition, manual searching was conducted for articles published up to April 6, 2020, using MeSH and free text keywords with no language limitation. Articles were screened, categorized, and extracted for relative data. Data were reported in a descriptive manner. Among 234 articles, 9 were selected for review of the inclusion criteria. No published original articles were found regarding the efficacy of ozone therapy on COVID-19. Five review studies were found in which the potential role of systemic ozone therapy was concluded to be effective in controlling COVID-19 because of its antiviral, oxygenation, anti-inflammatory, oxidation balancing, and immunomodulation effects. Three ongoing clinical trials were registered in China. A preliminary report of an ongoing study in Italy on 46 patients (11 intubated and 35 non-intubated) showed that in 39 (84%) of the patients, an improvement was seen. In spite of the promising background data, as well as the expert opinions and a preliminary report indicating the effectiveness of ozone, there is still not enough evidence to confirm this as a viable treatment option for COVID-19.

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.

Insights on the mechanisms of action of ozone in the medical therapy against COVID-19.

An increasing amount of reports in the literature is showing that medical ozone (O3) 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 O3 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 O3 should act on COVID-19. The knowledge on how O3 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.

Old Treatment for a New Disease: Can Rectal Ozone Insufflation Be Used for COVID-19 Management? A Case Report.

COVID-19 is a newly discovered deadly disease with no proven definitive treatment until now. It is now proved that it can affect different body organs which necessitate intensive care management. Ozone (O3) therapy was used before for treating various viral infections like hepatitis B, human immune deficiency virus (HIV), and Ebola viruses. O3 also can manage hypoxia and increase tissue oxygenation, besides its anti-inflammatory and immunomodulatory properties which may have an important role in the management of cytokine storm. We used rectal O3 insufflation therapy assuming that it may have a beneficial role in the management of COVID-19 disease. Two sessions of rectal O3 therapy were given to a 60-year-old female patient who was confirmed COVID-19 positive. Before applying O3 therapy, she was hypoxic (sPO2:90%) despite mechanical ventilation with high fraction inspired oxygen (FiO2:90%). After therapy, she was markedly improved and discharged to the inpatient ward and then discharged home on day 10 post-admission. Another 40-year-old male patient who was confirmed COVID-19 positive and was home isolated received one session of O3 therapy. Before therapy, he was hypoxic (sPO2:85% on room air and 95% with O2 face mask 5 L/min). The patient showed gradual improvement over the next 3 days after therapy and becomes oxygen-independent (sPO2 became 94-97% on room air). No adverse effects were noticed in both cases. Rectal O3 insufflation can be used safely as adjuvant management for patients with COVID-19 disease.