Long COVID affects an estimated 65 million people worldwide per the WHO 2024 post-COVID condition update. See detailed Shamir long-COVID RCT analysis for the full Shamir-RCT methodology analysis.
Hyperbaric oxygen therapy keeps surfacing as a possible treatment, with promising trial data and growing patient demand. The honest read is that the evidence is real but the regulatory and reimbursement picture is not.
This guide covers what the clinical literature actually shows, what HBOT is doing biologically, and where the off-label gap sits in 2026.
The Clinical Evidence
Sham-Controlled Randomized Trial
The strongest single piece of evidence comes from a sham-controlled trial run by Shamir Medical Center in Israel.
- Protocol: 40 sessions at 2.0 ATA, 100% oxygen, 90 minutes per session, 5 days per week for 8 weeks
- Results: Significant improvements in global cognition, attention, executive function, sleep, pain, and psychiatric symptoms versus sham group per Zilberman-Itskovich et al., Scientific Reports 2022
- Sample size: 73 patients, 37 HBOT vs 36 sham
- Safety: Well tolerated; no serious adverse events
The 1-year follow-up was published in Hadanny et al., Scientific Reports 2024 and confirmed that patient-reported improvements were maintained post-treatment.
Systematic Reviews
A 2024 Frontiers in Medicine narrative review of HBOT for long COVID neurological pathophysiology summarized the mechanistic case and identified the Shamir RCT as the leading clinical evidence.
A separate 2023 systematic review in Cureus flagged the small overall trial count and called for larger multi-center replications.
What's Still Missing
The Shamir RCT is one site, one team, and one protocol. Independent replication has not yet been published.
The NICE long COVID guidance NG188 (last updated 2024) does not recommend HBOT as standard care. The CDC long COVID clinical guidance (2024) is similarly silent on HBOT.
How HBOT Addresses Long COVID Pathophysiology
Long COVID involves several overlapping mechanisms — microvascular dysfunction, neuroinflammation, mitochondrial impairment, and possible viral persistence per Davis et al., Nature Reviews Microbiology 2023.
Tissue Oxygenation
At 2.0 ATA on 100% oxygen, dissolved plasma oxygen rises roughly 15-fold per Henry's Law calculations in StatPearls HBOT Physiology (2024).
That helps push oxygen through tissue beds where capillary flow is compromised by microclotting, which Pretorius and colleagues documented in Cardiovascular Diabetology 2021.
Neuroinflammation
HBOT modulates several neuroinflammatory markers including TNF-alpha and IL-6 per the 2024 Frontiers in Medicine review.
SPECT imaging in the Shamir trial showed increased cerebral blood flow in regions associated with cognition. That's a measurable physiological change, not just patient-reported improvement.
Mitochondrial Function
Chronic fatigue in long COVID has been linked to impaired mitochondrial bioenergetics. HBOT's effect on mitochondrial markers in long COVID is still preliminary but the mechanistic case is consistent with the broader literature on hyperoxic preconditioning.
Treatment Protocol Used in Trials
The Shamir protocol is the one the published evidence actually supports.
- Pressure: 2.0 ATA
- Oxygen: 100% medical grade
- Session length: 90 minutes including pressurization and depressurization
- Frequency: 5 sessions per week
- Total sessions: 40
- Duration: 8 weeks
- Equipment: Medical-grade hard-shell monoplace chamber
Soft-shell home chambers operating at 1.3 ATA on concentrated (not 100%) oxygen don't replicate the trial conditions per the FDA Safety Communication on home HBOT (2021).
Cost in 2026
Long COVID is not on the UHMS 15th Edition Indications list (2025), which is the document insurance carriers reference.
- Private clinic cash pay: $250-$600 per session, or $10,000-$24,000 for the 40-session protocol
- Insurance coverage: Denied under CMS NCD 20.29; commercial payers mirror Medicare
- HSA/FSA: Generally eligible if a treating physician documents medical necessity, though plan rules vary
Frequently Asked Questions
Is HBOT FDA-approved for long COVID?
No. The FDA Safety Communication (2021, reaffirmed 2024) lists 13 cleared HBOT indications and long COVID is not among them. The UHMS 15th Edition Indications (2025) similarly does not include long COVID. Any clinic offering HBOT for long COVID is offering an off-label treatment. That doesn't mean it doesn't work; it means it has not cleared the regulatory bar.
Does insurance cover HBOT for long COVID?
Generally no. Coverage hinges on the ICD-10 code submitted with the claim. Long COVID codes (U09.9 and related) fall outside the 14-indication list in CMS NCD 20.29. Commercial carriers including Aetna, Cigna, UnitedHealthcare, and Blue Cross Blue Shield mirror the CMS list. Appeals occasionally succeed but the baseline expectation in 2026 is denial.
How strong is the evidence?
There is one well-designed sham-controlled RCT from Shamir Medical Center, a longitudinal follow-up from the same group, and multiple narrative reviews. There is no independent replication yet from a different research team. The Cochrane Collaboration has not published a definitive review on HBOT for long COVID as of 2026.
Will home soft-shell chambers work?
The published clinical evidence used hard-shell chambers at 2.0 ATA on 100% oxygen. Home chambers at 1.3 ATA on concentrated oxygen don't replicate those conditions. The FDA Safety Communication on home HBOT (2021) makes clear that mild HBOT devices are not equivalent to clinical-grade chambers. There is no published trial data showing benefit at home chamber pressures for long COVID.
When should treatment start?
There's no documented window. The Shamir RCT enrolled patients with symptoms lasting months to years. Earlier treatment may prevent symptom entrenchment but the trial data show benefit even in patients with prolonged symptoms.
Related Reading
- HBOT Insurance Coverage in 2026: 14 Approved Indications Decoded
- How to Find a Legitimate HBOT Clinic Near You
- HBOT 40-Session Protocol: Why It's the Standard
Find HBOT Centers Near You
Browse our directory of UHMS-accredited HBOT centers to find a clinical-grade facility that can run a 40-session protocol under physician supervision.
-- The HBOT Finder Team
Medical Disclaimer: This article is for informational purposes only and does not constitute medical advice. Long COVID treatment should be supervised by a qualified physician. HBOT for long COVID is an off-label use not cleared by the FDA and not covered by most insurance.
Editorial Disclosure: HBOT Finder maintains editorial independence. We do not accept paid placements in our clinic directory.