Evaluating the Effectiveness of Intravenous Ozonated Normal Saline in the Treatment of Severe COVID-19 Disease: A randomized control trial
Authors: Janadliean Amir , Salmanzadeh Shokrollah , Nashibi Roohangiz , Alavi Seyed Mohammad , Moogahi Sasan , Bitaraf Saied 
Published: June 2023

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. Methods: 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 μg/ 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. Results: 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: 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.