HBOT for Long COVID: 2026 Clinical Trial Results & Patient Outcomes Data

The Landmark Tel Aviv RCT

A 2022 randomized controlled trial from Tel Aviv found that 40 HBOT sessions improved cognitive function (d=0.50), psychiatric symptoms (d=0.64), pain interference (d=0.74), and energy (d=0.52) in long COVID patients vs. sham. Quality of life gains held at 1.3 years post-treatment. Long COVID affects 10-30% of people who contract SARS-CoV-2, and this trial remains the strongest evidence for any single intervention.

Study Design

Zilberman-Itskovich et al. (2022, published in Scientific Reports) conducted a randomized, double-blind, sham-controlled trial at the Sagol Center for Hyperbaric Medicine and Research.¹ Key design elements:

• Participants: 73 patients with documented post-COVID symptoms lasting 3+ months
• Treatment group: 40 HBOT sessions at 2.0 ATA, 90 minutes each, 5 days/week for 8 weeks
• Sham control: 40 sessions in the same chamber at ambient pressure with room air, designed to be indistinguishable from real treatment
• Primary outcomes: Neurocognitive function, psychiatric symptoms, quality of life
• Objective imaging: Brain MRI with perfusion sequences before and after treatment

Key Results

“HBOT improved global cognitive function (d=0.50), psychiatric symptoms (d=0.64), pain interference (d=0.74), and energy and fatigue (d=0.52) compared to sham in 73 long COVID patients. Brain MRI confirmed increased cerebral perfusion in frontal and insular regions.”
Zilberman-Itskovich et al., Scientific Reports, 2022

Brain Imaging Findings

Perhaps the most compelling evidence from the trial was the objective brain imaging data. MRI perfusion sequences showed statistically significant increases in cerebral blood flow in frontal and temporal brain regions in the HBOT group, but not the sham group. Affected regions included the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiata. These are the same regions commonly affected in long COVID and correspond to the cognitive domains that improved on neuropsychological testing.

Follow-Up Data: Do Improvements Last?

Hadanny et al. (2024) published follow-up data on the original Tel Aviv cohort, assessing 31 patients an average of 486 days after treatment ended.² Quality of life improvements were maintained at the same magnitude as short-term outcomes. Sleep improvements held at effect sizes of 0.47-0.79 across five domains. Pain interference persisted at an effect size of 0.83. This is the first evidence that HBOT produces durable neuroplastic changes rather than temporary symptomatic relief in long COVID patients.

“Quality of life improvements after 40 HBOT sessions for long COVID were maintained at the same magnitude 1.3 years after treatment ended. Pain interference persisted at effect size 0.83.”
Hadanny et al., Scientific Reports, 2024

What Does the Research Say?

A 2026 comprehensive literature analysis by Zoccali and colleagues reviewed all studies published between January 2021 and October 2025.³ They identified 21 studies: 10 RCTs, 8 systematic reviews, 1 case report, and 3 molecular/mechanistic studies. This makes long COVID one of the most studied off-label HBOT applications.

A 2024 systematic review by Wu and colleagues⁴ and a 2025 PROSPERO-registered review by Zamora and colleagues⁵ both concluded that HBOT improves cognition, fatigue, quality of life, and neuropsychiatric symptoms in long COVID patients, with minimal serious adverse effects.

Registry Data: The Real-World Picture

A 2025 prospective registry by van Berkel and colleagues tracked 232 long COVID patients.⁶ At 3-month follow-up, 56-63% showed clinically relevant improvement in SF-36 quality of life scores. Cognitive symptoms improved most. However, 13-19% experienced clinically meaningful deterioration. This is the most important real-world data point: the majority improve, but a meaningful minority get worse.

Biomarker Evidence

Multiple studies have examined the biological mechanisms behind HBOT’s effects in long COVID. A 2026 biomarker review⁹ found that HBOT reduces pro-inflammatory cytokines including IL-6 and TNF-alpha while increasing the anti-inflammatory cytokine IL-10. Antioxidant activity (SOD) improved and reactive oxygen species decreased. A 2026 Vietnamese study of 51 patients⁸ found that normal cerebral blood flow normalized from 37% to 78% of patients after 14 HBOT sessions at 2.2 ATA, with DASS-21 anxiety scores improving from 10.08 to 7.13 and quality of life rising from 0.749 to 0.942 on the EQ-5D-5L.

The Dose-Response Issue

Two 2025 RCTs using 10-session protocols found no significant benefit. The HOT-LoCO trial (n=80, 2.4 ATA)¹⁰ and the Belgian D’hoore trial (n=101, 2.5 ATA)¹¹ both returned null results. The only positive sham-controlled RCT used 40 sessions. This dose-response relationship is the critical clinical insight: 10 sessions appears insufficient regardless of pressure.

What Does the HBOT Protocol Look Like?

The Tel Aviv protocol that produced positive results used:

• Pressure: 2.0 ATA (requires a medical-grade hard chamber)
• Oxygen: 100% medical-grade oxygen via mask
• Session duration: 90 minutes
• Frequency: 5 sessions per week
• Total course: 40 sessions over 8 weeks

What This Means for Patients

• Protocol matters: The evidence only supports 40+ sessions at 2.0 ATA in a hard chamber. Soft chambers at 1.3 ATA and 10-session courses have no positive evidence for long COVID.
• Not everyone responds: Registry data shows 13-19% of patients worsen. Patient selection and monitoring matter.
• Cost: A 40-session course costs approximately $8,000-$16,000 out of pocket. Long COVID is not an FDA-cleared indication and is not covered by major insurers.
• Source concentration: Most positive evidence comes from the Efrati/Hadanny group at Tel Aviv. Independent replication is needed.

1. Zilberman-Itskovich S, Catalogna M, Sasson E, et al. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Sci Rep. 2022;12:11252. DOI: 10.1038/s41598-022-15565-0. PMID: 35821512.
2. Hadanny A, Zilberman-Itskovich S, Catalogna M, et al. Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial. Sci Rep. 2024;14:3604. DOI: 10.1038/s41598-024-53091-3. PMID: 38360929.
3. Zoccali F, Fratini C, Pennacchia F, et al. Hyperbaric Oxygen Therapy on Long COVID Symptoms: A Breath of Fresh Air. Diseases. 2026;14(2):60. DOI: 10.3390/diseases14020060. PMID: 41745098.
4. Wu BQ, Liu DY, Shen TC, et al. Effects of Hyperbaric Oxygen Therapy on Long COVID: A Systematic Review. Life. 2024;14(4):438. DOI: 10.3390/life14040438. PMID: 38672710.
5. Zamora F, Santos AC, Zamora AV, et al. Hyperbaric Oxygen Treatment for Long-COVID syndrome: A Systematic Review of Current Evidence on Cognitive Decline. Undersea Hyperb Med. 2025. DOI: 10.22462/748. PMID: 41223394.
6. van Berkel J, Lalieu RC, Joseph D, et al. Hyperbaric oxygen therapy for long COVID: a prospective registry. Sci Rep. 2025. DOI: 10.1038/s41598-025-11539-0. PMID: 40759992.
7. Leitman M, Fuchs S, Tyomkin V, et al. The effect of hyperbaric oxygen therapy on myocardial function in post-COVID-19 syndrome patients. Sci Rep. 2023;13:9579. DOI: 10.1038/s41598-023-36570-x. PMID: 37301934.
8. Ha Nguyen Thi Hai et al. Behavioral and Mental Disorders in Patients after COVID-19 and Results of HBOT. J Marine Medical Society. 2026. DOI: 10.4103/jmms.jmms_59_25.
9. Soedarsono S, Wijaya RA, Biutifasari V. Potential Biomarkers and Inflammatory Modulation of HBOT in Long COVID. Jurnal Respirasi. 2026. DOI: 10.20473/jr.v12-i.1.2026.90-96.
10. Kjellberg A, et al. HOT-LoCO trial. BMJ Open. 2025. PMID: 40228859.
11. D’hoore L, Germonpre P, Hassler A, et al. Effect of normobaric and hyperbaric hyperoxia treatment on symptoms and cognitive capacities in Long COVID patients. Diving Hyperb Med. 2025;55(2):104-113. DOI: 10.28920/dhm55.2.104-113. PMID: 40544138.

Seph Fontane Pennock

Author

Seph Fontane Pennock is the founder of BaricBoost.com and Regenerated.com, a clinic directory for regenerative medicine serving 10,000+ providers across the United States. He previously built and sold PositivePsychology.com, which grew to 19 million users and became the largest evidence-based positive psychology resource on the web. Seph brings direct experience as an HBOT patient, having completed protocols at clinics across three continents while navigating mold illness, systemic inflammation, and autoimmune conditions. His treatment journey includes hyperbaric oxygen therapy, peptide protocols, NAD+ therapy, and consultations with specialists from Dubai to Cape Town to Mexico. This combination of entrepreneurial track record and lived patient experience shapes everything published on BaricBoost.com. Every article is grounded in peer-reviewed research, informed by real clinical encounters, and written for patients making high-stakes treatment decisions. Seph's focus is on bringing transparency, scientific rigor, and practical guidance to the hyperbaric oxygen therapy space.

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