Benefits of ozone on mortality in patients with COVID-19: A systematic review and meta-analysis

Background: why researchers looked at ozone and COVID-19

During the COVID-19 pandemic, clinicians looked for adjuvant therapies that might support standard hospital care. Ozone therapy has a long history of use in infectious disease, thought to work through its antioxidant effects and by improving the delivery of oxygen to poorly oxygenated tissues. This systematic review and meta-analysis set out to assess whether adding ozone therapy to conventional treatment was associated with lower mortality, and with related outcomes, in people hospitalised with COVID-19.

Study design: eight controlled trials pooling 371 patients

The authors searched PubMed, Embase, the Cochrane Library and clinicaltrials.gov, with no language restriction. They included prospective controlled trials that compared ozone therapy against placebo or standard care alone. Eight trials, enrolling a combined 371 participants, met the inclusion criteria. Results were pooled statistically, with treatment effects expressed as risk ratios (RR) for events such as death and PCR positivity, and as weighted mean differences (WMD) for length of hospital stay, each reported with 95% confidence intervals.

Findings: lower pooled mortality, PCR positivity and hospital stay

Across the eight trials, adjuvant ozone therapy was associated with lower mortality than the comparator (RR 0.38, 95% confidence interval 0.17 to 0.85). It was also associated with a shorter hospital stay, by an average of roughly 1.6 days (WMD -1.63 days, 95% confidence interval -3.05 to -0.22 days), and with reduced PCR positivity (RR 0.07, 95% confidence interval 0.01 to 0.34). The confidence intervals for the mortality and PCR outcomes are wide, which reflects the small number of events and participants involved.

What the authors concluded

The authors concluded that, in this pooled analysis, ozone therapy was associated with significantly reduced mortality, PCR positivity and length of stay in hospitalised patients with COVID-19, and they suggested that ozone therapy could be considered as an adjuvant option for these patients. They framed ozone as an addition to standard care rather than a replacement for it.

Limitations of this study

The evidence base is small: eight trials and only 371 patients in total, with several individual studies being small and conducted early in the pandemic when standard care was still evolving. The trials varied in how ozone was delivered, so the pooled estimate combines somewhat different protocols. The wide confidence intervals mean the true size of any benefit is uncertain, and the potential for bias in smaller controlled trials cannot be excluded. Findings of this kind should be read as hypothesis-generating and confirmed in larger, well-controlled randomised trials. Ozone therapy is a complementary, adjuvant approach used alongside conventional medical treatment, not a cure for COVID-19, and any use should be discussed with a qualified healthcare professional.