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About: The aim of this study is to evaluate the effectiveness of rectal ozone (O(3)) in COVID-19 patients with severe pneumonia admitted at Hospital Universitario Santa Cristina, Madrid. In a before-and-after study, four patients admitted with severe bilateral pneumonia due to COVID-19 were treated with rectal ozone and confirmed with (+) RT-PCR for SARS-CoV-2 and evaluated afterwards. The analyzed outcome variables were as follows: (a) clinical improvement (O(2) saturation and O(2) supply); (b) biochemical improvement (fibrinogen, D-dimer, urea, ferritin, LDH, IL-6, and CRP); (c) radiological improvement. The treatment protocol consisted of 5 sessions (1 session/day) of intra-rectal ozone, applied in a volume of 100 mL and a concentration of 35 μg/mL. The Protocol was previously approved by the Hospital’s Health Care Ethics Committee (CEAS) (Report 15/4/2020) for compassionate use in the face of this exceptional pandemic situation, and prior informed consent was obtained from the patient/legal representative. The patients improved oxygen saturation, as observed by the lower number of desaturations and the lower supply of O(2). Biomarkers of inflammation decreased (fibrinogen, D-dimer, urea, ferritin, LDH, IL-6, and CRP). Finally, the radiological signs of bilateral viral pneumonitis improved between 1 and 2 grades based on Taylor’s radiological scale. Rectal ozone decreases O(2) supply and improves O(2) saturation, decreases inflammation biomarkers, and improves Taylor’s radiological grade in patients with severe COVID-19 pneumonia. Rectal ozone is a safe, effective, cheap, and simple alternative capable of acting on the SARS-CoV-2 virus, and it is presented as an adjunctive therapeutic option to consider in the management of severe bilateral COVID-19 pneumonia.

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