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. Materials and methods: 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 6procedures performed every other day. The second group included 30patients 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-y, TNF-a, 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). Results: 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-a/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: 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.

COVID-19, pro- and anti-inflammatory cytokines, cytokine storm, systemic ozone therapy