Key Takeaways
- Zilberman-Itskovich et al. 2022 is the first sham-controlled RCT of HBOT for long COVID, published in Scientific Reports.
- The protocol: 40 sessions at 2.0 ATA over 60 days in adults with cognitive symptoms persisting 3+ months after COVID-19.
- The active HBOT arm showed significant improvement in cognitive function, 6-minute walk distance, quality of life, and perfusion MRI; the 1.03 ATA sham arm showed no significant change.
- HBOT for long COVID remains off-label in the US — typically $6,000–$18,000 out-of-pocket for a full course.
- The findings have driven replication trials at the Efrati Lab, Mayo Clinic, and EU academic centres; UHMS review for formal inclusion is anticipated.
Background
Long COVID (post-acute sequelae of SARS-CoV-2, or PASC) emerged as a major clinical problem in 2021–2022. A subset of patients continued to experience cognitive deficits, chronic fatigue, and reduced exercise tolerance for months after their initial infection. Mechanistic hypotheses coalesced around neuroinflammation, mitochondrial dysfunction, and microvascular injury — all biological targets that hyperbaric oxygen therapy had already shown effects on in other neurological contexts.
The Trial
Zilberman-Itskovich et al. (2022) conducted the first randomised, sham-controlled trial of HBOT for long COVID at the Sagol Center for Hyperbaric Medicine in Israel. Seventy-three adults with post-COVID cognitive symptoms persisting at least three months were randomised to either active HBOT (2.0 ATA, 90-minute sessions with air breaks) or sham (1.03 ATA with placebo gas), for 40 sessions over 60 days.
Results
The active HBOT arm showed statistically significant improvement across multiple domains:
- Cognitive function — measurable gains on attention, executive function, and processing speed batteries.
- Physical measures — improved 6-minute walk distance.
- Quality of life — significant gains on validated QoL questionnaires.
- Neuroimaging — perfusion MRI showed improved cerebral blood flow in previously hypoperfused regions.
The sham arm showed no significant change on the same measures.
What This Means Clinically
The Zilberman-Itskovich trial established HBOT at 2.0 ATA as a research-stage treatment with Class II evidence for long COVID cognitive symptoms. It is not FDA-approved for this indication and remains off-label — meaning most US patients pay out of pocket. However, the trial is methodologically strong and has influenced clinical practice at the Efrati-affiliated clinics and several US centres.
Caveats
- Single-centre trial — replication at other sites is pending.
- Follow-up was limited to end-of-course; long-term durability of gains is not yet characterised.
- Full-course HBOT is a 40-session commitment and typically out-of-pocket in most jurisdictions.
Where It Fits
For patients with persistent long COVID cognitive symptoms more than three months after infection, HBOT at 2.0 ATA is one of the few interventions with RCT-level evidence. It is best considered alongside — not instead of — graded exercise, cognitive rehabilitation, and pharmacologic management of specific symptoms.
Frequently Asked Questions
How soon after COVID can HBOT help?
The Zilberman-Itskovich trial enrolled patients with symptoms persisting at least 3 months after infection. There is no established lower bound; some clinicians treat earlier. HBOT is studied for persistent long COVID, not acute COVID-19.
What symptoms respond best?
Cognitive symptoms (brain fog), chronic fatigue, and physical measures (6-minute walk) showed the strongest response in the trial. Specific symptoms like dysautonomia, loss of taste/smell, and chronic cardiopulmonary issues have less direct evidence.
Does insurance cover HBOT for long COVID?
No — long COVID HBOT is off-label and not covered by CMS/Medicare or most US private insurers. Patients typically pay out-of-pocket at private hyperbaric clinics.
What pressure is used?
The Zilberman-Itskovich protocol uses 2.0 ATA — the standard research pressure for Efrati-lab neurological HBOT. 1.3 ATA soft-shell protocols have substantially weaker evidence for long COVID.
