Overview
The 2022 Zilberman-Itskovich et al. randomised controlled trial (Efrati group) demonstrated statistically significant improvements in cognitive function, fatigue, sleep, and psychiatric symptoms in long COVID patients treated with 40 HBOT sessions at 2.0 ATA versus sham. This is the strongest HBOT evidence for post-viral conditions to date.
Long COVID — the WHO term is post-COVID-19 condition, also called PASC (post-acute sequelae of SARS-CoV-2) — affects an estimated 10–30% of COVID-19 survivors with symptoms persisting at least three months after infection. Core features include cognitive dysfunction ("brain fog"), chronic fatigue, exercise intolerance, dyspnoea, and dysautonomia. Pathophysiological hypotheses include neuroinflammation, mitochondrial dysfunction, microvascular injury, and persistent immune dysregulation.
The Zilberman-Itskovich et al. 2022 trial (published in Scientific Reports) is the first and most-cited RCT of HBOT for long COVID. The study randomised 73 adults with post-COVID cognitive symptoms persisting at least three months to either active HBOT (2.0 ATA, 90-minute sessions) or sham (1.03 ATA with placebo gas), for 40 sessions over 60 days. The active arm showed significant improvement across cognitive function, physical measures (6-minute walk), quality of life, and perfusion MRI findings. The sham arm showed no significant change.
The findings have been clinically influential. Several US and international hyperbaric centres have initiated long COVID HBOT programmes. Replication trials are underway at the Efrati Lab, Mayo Clinic, Harvard-affiliated centres, and EU academic hospitals.
How HBOT Works for This Condition
HBOT addresses several hypothesised long COVID mechanisms. Elevated plasma oxygen reverses the microvascular hypoxia hypothesised to drive brain fog and exercise intolerance. Reduced microglial activation and shifted macrophage polarisation address neuroinflammation. Improved mitochondrial function supports energy production in post-infectious fatigue. The Zilberman-Itskovich trial documented objective perfusion MRI changes in brain regions corresponding to clinical improvement — supporting a vascular/perfusion mechanism as central.
GRADE Evidence Rating
Zilberman-Itskovich 2022 sham-controlled RCT at 2.0 ATA shows cognitive + imaging benefit. Single-centre; multicentre replication pending.
| GRADE Domain | Assessment |
|---|---|
| Risk of bias | Low |
| Consistency | Single trial |
| Directness | Direct |
| Precision | Moderate |
GRADE methodology: Grading of Recommendations Assessment, Development and Evaluation. See GRADE Working Group.
Clinical Protocol
| Typical protocol | 40 sessions at 2.0 ATA, 90 minutes each, 5 days/week |
|---|---|
| Evidence level | RCT (Phase 2) — Promising evidence |
| FDA status | Not FDA-approved |
The Zilberman-Itskovich protocol: 40 sessions over 60 days, each 90 minutes at 2.0 ATA with scheduled 5-minute air breaks every 20 minutes. Pre- and post-course assessment includes cognitive batteries (attention, executive function, processing speed), physical measures (6-minute walk), quality of life questionnaires, and perfusion MRI.
Evidence Base
The Zilberman-Itskovich 2022 trial is methodologically strong (sham-controlled, pre-specified outcomes, objective imaging). Single-centre; replication is pending. Several additional smaller studies and open-label trials have reported positive results. UHMS has not yet reviewed long COVID for formal inclusion, but the pressure for review is building given the magnitude of the long COVID population.
Patient Perspective
Long COVID patients report cognitive gains, reduced fatigue, and improved exercise tolerance across a 40-session course. Response is not universal; approximately 20–30% of participants in the Zilberman-Itskovich trial did not show meaningful improvement. Treatment is typically out-of-pocket; a full course costs $6,000–$18,000 in US private clinics. Many patients travel to Efrati-affiliated centres in Israel or specialised US hyperbaric clinics.
Cautions & Considerations
- Off-label; not covered by US insurance or CMS.
- Response variable — not all patients benefit.
- Cost of a full course is substantial.
- Standard HBOT contraindications apply.
- Daily attendance for approximately 8 weeks.
Key Research & References
- Zilberman-Itskovich et al. 2022 (Scientific Reports)
- Various replication trials underway
Indexed Studies for This Condition
Linked entries in the HBOT Studies Database.
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 for acute COVID-19.
Does HBOT work for all long COVID symptoms?
The strongest evidence is for cognitive symptoms (brain fog), fatigue, and physical measures. Specific symptoms like dysautonomia, loss of taste/smell, and chronic cardiopulmonary issues have less direct evidence.
Can I combine HBOT with other long COVID treatments?
HBOT is routinely combined with graded exercise, cognitive rehabilitation, and symptomatic management. There are no established pharmacological interactions, though chemotherapy and some specific medications remain HBOT contraindications.
Research disclaimer: This article summarises published research for educational purposes only. Nothing here is medical advice. HBOT is a prescription medical treatment that must be administered under physician supervision in appropriately certified chambers. Discuss any treatment decisions with a qualified clinician.