Effect of Rectal Ozone (O3) in Severe COVID-19 Pneumonia

Background

Severe COVID-19 pneumonia can progress to profound hypoxaemia and an overwhelming inflammatory response, sometimes called a cytokine storm, which drives lung damage and poor outcomes. Early in the pandemic, clinicians in Madrid were treating patients with few proven adjunctive options beyond standard supportive care. Ozone therapy - already used in some European countries for other conditions - was proposed as a low-cost, easily administered complementary measure that might help modulate inflammation and oxygenation while standard treatments took effect. This report describes a compassionate-use trial of rectal ozone insufflation in patients with severe bilateral COVID-19 pneumonia.

Study design

Researchers at Hospital Universitario Santa Cristina in Madrid treated four patients admitted with severe, bilaterally confirmed COVID-19 pneumonia. Each patient received rectal ozone insufflation - a technique in which a measured mixture of oxygen and ozone gas is introduced into the rectum, where it is absorbed across the intestinal mucosa - alongside their standard hospital care. This was a before-and-after design: each patient's own measurements prior to treatment served as the comparison point for their measurements afterwards, rather than a separate control group. The researchers tracked blood oxygen saturation, a panel of inflammation biomarkers (blood markers that rise when the body is fighting infection or inflammation), and chest imaging scored using the Taylor radiological grading system, which rates the severity of pneumonia visible on scans.

Findings

Following rectal ozone treatment, all four patients showed improved blood oxygen saturation. Inflammation biomarkers fell across the group, indicating a reduction in the inflammatory response associated with severe COVID-19. Chest imaging also showed improvement, with patients' Taylor radiological grade scores decreasing after treatment, reflecting less extensive pneumonia on repeat scans. No data on a comparison group receiving standard care alone were reported within this preliminary case series, so these changes cannot be directly attributed to ozone alone versus the natural course of treatment.

What the authors concluded

The authors concluded that rectal ozone appeared to be a safe, inexpensive, and simple intervention in this small group of patients, and suggested it may act against the SARS-CoV-2 virus and its downstream effects on the lungs. They proposed rectal ozone as an adjunctive therapeutic option worth considering alongside standard care in the management of severe bilateral COVID-19 pneumonia, while calling for further, larger studies to confirm these preliminary observations.

Limitations of this study

This was a preliminary report on just four patients, with no control group and no randomisation, so it cannot establish whether rectal ozone caused the improvements seen or how much standard hospital care alone contributed. The before-and-after design is particularly vulnerable to natural fluctuations in COVID-19 pneumonia severity over time. The study was conducted at a single centre under compassionate-use, emergency-pandemic conditions, which limits how confidently the findings can be generalised to other settings or patient groups. Larger, controlled trials are needed before rectal ozone could be considered a validated treatment for severe COVID-19 pneumonia.