Major Ozone Autohaemotherapy for Long COVID: A Pilot Randomised Controlled Trial of 73 Patients (2024)

Background

Post-acute sequelae of COVID-19 - long COVID - is the persistence of symptoms such as fatigue, breathlessness and reduced exercise capacity after the infection itself has cleared. By 2023, earlier reports had suggested that ozone therapy might relieve post-COVID fatigue, but all of them were uncontrolled series in which every patient received the treatment. Without a comparison group, it is impossible to say how much of any improvement would have happened anyway.

A team from the Department of Respiratory and Critical Care Medicine at Renmin Hospital of Wuhan University set out to close that gap with a randomised controlled trial. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300070566) and funded by the National Natural Science Foundation of China.

Study design

This was a prospective, randomised, controlled clinical trial run between May and September 2023. Seventy-three eligible patients with long COVID were randomly assigned to one of two groups: 35 received major ozone autohaemotherapy - blood drawn, mixed with a measured oxygen-ozone gas mixture and returned by drip - in addition to conventional treatment, and 38 received conventional treatment alone.

Before and after the intervention the researchers measured a symptom score, pulmonary function, six-minute walk distance, and a panel of blood tests covering haematology, biochemistry, immune cell counts, coagulation and inflammatory markers. A patient was counted as a responder if their symptom score fell by at least half.

The abstract does not state the ozone concentration, the number of sessions or whether the trial was blinded. Because the control group received no sham procedure, it is likely that patients knew which group they were in. This was a hospital-based procedure delivered by clinicians; it is a description of what was studied, not a set of instructions.

Findings

Both groups improved, but the ozone group improved more. Twenty-five of the 35 patients given ozone (71%) had their symptom score at least halved, compared with 17 of the 38 (45%) on conventional treatment alone (p = 0.0325).

Breathing and walking. Symptom scores, tidal volume (the volume of air moved with each normal breath) and predicted six-minute walk distance all improved significantly in the ozone group.

Blood markers. Coagulation and inflammatory indicators improved in the ozone group, and the authors report that cellular immunity was "markedly" improved, with larger gains the longer the treatment continued. Patients with higher C-reactive protein at the start showed greater benefit.

Safety. The authors state that ozone autohaemotherapy "exhibited no adverse effect".

What the authors concluded

The authors conclude that combining major ozone autohaemotherapy with conventional treatment "was more effective than conventional therapy alone in improving symptoms, pulmonary function, inflammation, coagulation, and cellular immunity" in patients with long COVID.

Limitations of this study

We have worked from the published abstract, as the full paper is behind a paywall, so we cannot report the authors' own list of limitations, the ozone protocol, the exact symptom scale, the size of the changes in each measure, or how long after treatment the follow-up measurements were taken. We will update this summary if the full text becomes accessible.

What can be said from the abstract: this is a pilot trial of 73 people, which is small for a condition as varied as long COVID. There was no sham or placebo procedure, so the comparison is between having ozone and knowing you are not having it, which leaves room for expectation to influence symptom scores. The objective measures - walk distance, lung volume, blood markers - are less open to that influence, which is one reason they matter here.

The authors describe the trial as a pilot, which by convention means its purpose is to establish whether a larger definitive trial is worth running.

Long COVID should be diagnosed and managed with a doctor. Anyone considering ozone therapy alongside their care should discuss it with their own GP or specialist.

Related reading

Rectal Ozone Insufflation in Long COVID: A 12-Week Preliminary Study of 23 Patients (2026) - the same condition studied with the home route.

Major Ozone Autohaemotherapy in Post-COVID Syndrome: A Records Review of 40 Patients (2026)

Fatigue in Long COVID Treated with Oxygen-Ozone Autohaemotherapy: 100 Patients

How Ozone Therapy Works: The Science in Plain Words

He Y, Liu X, Zha S, Wang Y, Zhang J, Zhang Q, Hu K. A pilot randomized controlled trial of major ozone autohemotherapy for patients with post-acute sequelae of COVID-19. International Immunopharmacology. 2024;139:112673. Published 30 September 2024. doi:10.1016/j.intimp.2024.112673