Compassionate Use of Rectal Ozone (O(3)) in Severe COVID-19 Pneumonia: a Case-Control Study

Fernández-Cuadros, Marcos Edgar; Albaladejo-Florín, María Jesús; Álava-Rabasa, Sandra; Gallego-Galiana, Juan; Pérez-Cruz, Gerardo Fabiel; Usandizaga-Elio, Isabel; Pacios, Enrique; Torres-García, David E.; Peña-Lora, Daiana; Casique-Bocanegra, Luz; López-Muñoz, María Jesús; Rodríguez-de-Cía, Javier; Pérez-Moro, Olga Susana

OBJECTIVES: To evaluate effect of rectal ozone in severe COVID-19 pneumonia and to compare it to standard of care (SOC). MATERIAL AND METHODS: In a case-control study, 14 patients with severe bilateral COVID-19 pneumonia (positive RT-PCR), treated with SOC and rectal ozone, were evaluated before-and-after treatment and compared with SOC (14 patients) in a 10-day follow-up period. Ozone protocol consisted of 8 sessions (1 session/day) of intra-rectal ozone (150 mL volume, 35 μg/mL concentration [5.25mg total dose]). The SOC protocol included O(2) supply, antivirals (Remdesivir), corticosteroids (Dexamethasone/Metilprednisolone), monoclonal antibodies (Anakinra/Tocilizumab), antibiotics (Azytromicine), and anticoagulants (Enoxaparine). Primary outcome variables were the following: (a) clinical (O(2) saturation and O(2) supply); (b) biochemical (lymphocyte count, fibrinogen, D-dimer, urea, ferritin, LDH, IL-6, and CRP); (c) radiological Taylor’s scale. Secondary outcome variables were the following: (a) hospitalization length of stay, (b) mortality rate. RESULTS: At baseline, ozone/SOC groups were not different on age, comorbidities, O(2) saturation, and O(2) supply. Patients in the ozone group improved O(2) saturation and decrease O(2) supply. SOC maintained O(2) saturation and required more O(2) supply. Lymphocyte count improved only in the ozone group and with statistical difference (p<0.05). Biomarkers of inflammation (fibrinogen, D-dimer, urea, LDH, CRP, and IL-6) decreased in both groups, but only significantly in favor of the ozone group (p<0.05). Ferritin showed a significant decrease in the ozone group but an increase on the SOC group. Radiological pneumonitis decreased on both groups but the decrease was only significant in the ozone group (p<0.0001). Mortality and length of stay, although not significant, were inferior in the ozone group. CONCLUSION: Compassionate use of rectal ozone improved O(2) saturation, reduced O(2) supply, decreased inflammation biomarkers, and improved Taylor’s radiological scale significantly when compared to the SOC group. Mortality and length of stay were inferior in the ozone group, but this difference was not significant.