Hyperbaric Oxygen Treatment of Long Covid: Review of the Evidence and Perspective
Main Article Content
Abstract
Hyperbaric oxygen therapy (HBOT) has emerged as an effective treatment for Long COVID, a condition affecting tens of millions of people in the US and characterized by persistent and debilitating symptoms following SARS-CoV-2 infection. This analysis explores the mechanisms and clinical evidence supporting the efficacy of HBOT in addressing the complex pathophysiology underlying Long COVID. The authors also discuss the social and economic consequences of this new disease, the barriers to accessing HBO treatment and they propose solutions to these barriers.
Mechanisms of Action:
- Anti-inflammatory effects: HBOT reduces
pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and elevates anti-inflammatory IL-10
- Endothelial protection: Improves endothelial function, enhances nitric oxide bioavailability, and attenuates oxidative stress
- Neuroplasticity: Stimulates stem cell mobilization, mitochondrial biogenesis, and synaptic plasticity
- Angiogenesis: Stimulates development of new small blood vessels in areas of lost microcirculation, relieves tissue and organ hypoxia, and restores function
- Immune Modulation: HBO inhibits abnormal activation of T and B Lymphocytes
Clinical Evidence:
- Randomized controlled trials using computerized cognitive battery testing and standardized SF-36 physical function metrics have demonstrated significant improvements in fatigue, cognitive function, attention, and quality of life.
- Case studies report reduced inflammation, oxidative stress, enhanced lung function and significant improvement in neurocognitive function in Long COVID patients treated with HBO.
- Durable benefits observed up to one-year post-treatment, with greatest improvements in most disturbed
- Controlled studies demonstrate the safety of HBO
The growing list of published scientific studies show that HBOT is effective and safe in treating Long COVID. The effectiveness of HBOT is correlated with its ability to target the likely underlying pathophysiology of Long COVID. Currently, HBOT is the only known single treatment that can improve or reverse the many symptoms across multiple organ systems that define Long COVID. These results have been verified and repeated from multiple clinical trials and case reports across the world. The improvement of these symptoms is also sustained long term.
Long COVID affects at least 25-50 million people in the US and up to 1 billion worldwide. The individual effects are varied and can be mild to severely debilitating. When the disease symptoms are profound, it removes people from the workforce, strains personal relationships, and may require around the clock care. It is estimated that the economic impact may be 100 billion in the US annually and up to two trillion globally.
To date, there is not a widely accepted and effective treatment for all the symptoms of Long COVID. This paper presents a review of current scientific studies that highlight hyperbaric oxygen as an effective treatment, a treatment that can reverse the symptoms of Long COVID in a six to eight-week period and has benefits sustained long term. The authors discuss reasons that this treatment currently sees only limited use and they discuss the current limited availability and cost associated with this treatment. They suggest an alternative form of HBOT implementation that would improve both access and affordability. If these last barriers can be overcome, HBO treatment could become the standard by which people recover from Long COVID.
Article Details
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
2. Huerne K, Filion KB, Grad R, Ernst P, Gershon AS, Eisenberg MJ. Epidemiological and clinical perspectives of long COVID syndrome. Am J Med Open. 2023;9:100033. doi:10.1016/j.ajmo.2023.100033
3. Tin A. How many Americans still haven't caught COVID-19? CDC publishes final 2022 estimates. CBS News. Published July 3, 2023. Accessed June 24, 2025. https://www.cbsnews.com/news/how-many-americans-havent-caught-covid-cdc-estimates/
4. Elflein J. Long COVID in the U.S. - statistics & facts. Statista. Published October 29, 2024. Accessed June 24, 2025.
5. Office of the Assistant Secretary for Health (OASH). Long COVID. U.S. Department of Health & Human Services. Published February 2024. Accessed June 24, 2025. https://us.pagefreezer.com/nl/wa/browse/0a7f82bb-be6e-448a-ae11-373d22c37842?url=https:%2F%2Fwww.hhs.gov%2Fsites%2Fdefault%2Ffiles%2Flong-covid-update-2024.pdf×tamp=2025-05-01T07:02:19Z
6. Backman I. COVID vaccines reduce long COVID risk, new study shows. Yale Medicine. Published September 2, 2024. Accessed June 24, 2025. https://www.yalemedicine.org/news/covid-vaccines-reduce-long-covid-risk-new-study-shows
7. Bornali Bhattacharjee, Peiwen Lu, Valter Silva Monteiro et al; Immunological and Antigenic Signatures Associated with Chronic Illnesses after COVID-19 Vaccination medRxiv2025.02.18.2532 2379; doi: https://doi.org/10.1101/2025.02.18. 25322379
8. Centers for Disease Control and Prevention (CDC). National Diabetes Statistics Report. CDC Diabetes. Published May 15, 2024. Accessed June 24, 2025. https://www.cdc.gov/diabetes/php/data-research/index.html
9. Centers for Disease Control and Prevention (CDC). Living with Long COVID. Published February 3, 2025. Accessed July 11, 2025. https://www.cdc.gov/covid/long-ter-effects/living-with-long-covid.html
10. 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(1):3604. Published February 15, 2024. doi:10.1038/s41598-024-53091-3
11. Al-Aly Z, Davis H, McCorkell L, et al. Long COVID science, research and policy. Nat Med. 2024;30:2148–2164. doi:10.1038/s41591-024-03173-6
12. Voruz P, Assal F, Péron JA. The economic burden of the post-COVID-19 condition: underestimated long-term consequences of neuropsychological deficits. J Glob Health. 2023;13:03019. Published May 5, 2023. doi:10.7189/jogh.13.03019
13. Katz AA, Wainwright S, Kelly MP, Albert P, Byrne R. Hyperbaric oxygen effectively addresses the pathophysiology of long COVID: clinical review. Front Med. Published February 14, 2024. Accessed June 24, 2025.
14. Schottlender N, Gottfried I, Ashery U. Hyperbaric oxygen treatment: effects on mitochondrial function and oxidative stress. Biomolecules. 2021;11(12): 1827. Published December 3, 2021. doi:10.3390/biom11121827
15. Chen L, Wang Y, Zhou H, Liang Y, Zhu F, Zhou G. The new insights of hyperbaric oxygen therapy: focus on inflammatory bowel disease. Precis Clin Med. 2024;7(1):pbae001. Published 2024 Jan 18. doi:10.1093/pcmedi/pbae001
16. Li Y, Zhang H, Liang Y, et al. Effects of hyperbaric oxygen on vascular endothelial function in patients with slow coronary flow. Cardiol J. 2018;25(1):106-112. doi:10.5603/CJ.a2017.0132
17. Miike T, Sakamoto Y, Sakamoto Y, et al. Influence of hyperbaric oxygen therapy on thrombus formation ability in humans. Undersea Hyperb Med. 2020;47(4):591-595. doi:10.22462/10.12.2020.8
18. Davis HE, McCorkell L, Vogel JM, et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21:133–146. doi:10.1038/s41579-022-00846-2
19. Katz AA, Wainwright S, Kelly MP, Albert P, Byrne R. Hyperbaric oxygen effectively addresses the pathophysiology of long COVID: clinical review. Front Med. Published February 14, 2024. Accessed June 24, 2025. Thom SR. Hyperbaric oxygen: its mechanisms and efficacy. Plast Reconstr Surg. 2011;127 Suppl 1(Suppl 1):131S-141S. doi:10.1097/PRS.0b013e3181fbe2bf
20. Kjellberg A, Abdel-Halim L, Hassler A, et al. Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial. BMJ Open. 2022;12(11):e061870. Published November 2, 2022. doi:10.1136/bmjopen-2022-061870
21. Robbins T, Gonevski M, Clark C, et al. Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention. Clin Med (Lond). 2021;21(6):e629-e632. doi:10.7861/clinmed.2021-0462
22. Leitman M, Fuchs S, Tyomkin V, Hadanny A, Zilberman-Itskovich S, Efrati S. The effect of hyperbaric oxygen therapy on myocardial function in post-COVID-19 syndrome patients: a randomized controlled trial. Sci Rep. 2023;13(1):9473. Published June 10, 2023. doi:10.1038/s41598-023-36570-x
23. Wu BQ, Liu DY, Shen TC, Lai YR, Yu TL, Hsu HL, Lee HM, Liao WC, Hsia TC. Effects of Hyperbaric Oxygen Therapy on Long COVID: A Systematic Review. Life (Basel). 2024 Mar 26;14(4):438. doi: 10.3390/life14040438. PMID: 38672710; PMCID: PMC11051078.
24. Zant AE, Figueroa XA, Paulson CP, Wright JK. Hyperbaric oxygen therapy to treat lingering COVID-19 symptoms. Undersea Hyperb Med. 2022 Third Quarter;49(3):333-339. doi: 10.22462/05.06.2022.7. PMID: 36001566.
25. Kitala D, Łabuś W, Kozielski J, Strzelec P, Nowak M, Knefel G, Dyjas P, Materniak K, Kosmala J, Pająk J, Czop J, Janda-Kalus B, Marona B, Nowak-Wróżyna A, Gierek M, Szczegielniak J, Kucharzewski M. Preliminary Research on the Effect of Hyperbaric Oxygen Therapy in Patients with Post-COVID-19 Syndrome. J Clin Med. 2022 Dec 30;12(1):308. doi: 10.3390/jcm12010308. PMID: 36615108; PMCID: PMC9821575.
26. Garred P, Madsen MB, Hyldegaard O, Hedetoft M. Hyperbaric oxygen treatment is associated with a decrease in cytokine levels in patients with necrotizing soft-tissue infection. Physiol Rep. Published March 14, 2021. Accessed June 24, 2025. https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy2.14757
27. 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. Published July 12, 2022. doi:10.1038/s41598-022-15565-0
28. Mrakic-Sposta S, Vezzoli A, Garetto G, Paganini M, Camporesi E, Giacon TA, Dellanoce C, Agrimi J, Bosco G. Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes. Metabolites. 2023 Sep 25;13(10):1032. doi: 10.3390/metabo13101032. PMID: 37887357; PMCID: PMC10608857.
29. Bhaiyat AM, Sasson E, Wang Z, Khairy S, Ginzarly M, Qureshi U, Fikree M, Efrati S. Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. J Med Case Rep. 2022 Feb 15;16(1):80. doi: 10.1186/s13256-022-03287-w. PMID: 35168680; PMCID: PMC8848789.
30. Kjellberg A, Abdel-Halim L, Hassler A, El Gharbi S, Al-Ezerjawi S, Boström E, Sundberg CJ, Pernow J, Medson K, Kowalski JH, Rodriguez-Wallberg KA, Zheng X, Catrina S, Runold M, Ståhlberg M, Bruchfeld J, Nygren-Bonnier M, Lindholm P. Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial. BMJ Open. 2022 Nov 2;12(11):e061870. doi: 10.1136/bmjopen-2022-061870. PMID: 36323462; PMCID: PMC9638753.
31. Hadanny A, Zilberman-Itskovich S, Catalogna M, Elman-Shina K, Lang E, Finci S, Polak N, Shorer R, Parag Y, Efrati S. Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial. Sci Rep. 2024 Feb 15;14(1):3604. doi: 10.1038/s41598-024-53091-3. PMID: 38360929; PMCID: PMC10869702.
32. Kjellberg A, Abdel-Halim L, Hassler A, El Gharbi S, Al-Ezerjawi S, Boström E, Sundberg CJ, Pernow J, Medson K, Kowalski JH, Rodriguez-Wallberg KA, Zheng X, Catrina S, Runold M, Ståhlberg M, Bruchfeld J, Nygren-Bonnier M, Lindholm P. Ten sessions of hyperbaric oxygen verses sham treatment in patients with long covid (HOT-LoCO): a randomised, placebo-controlled, double-blind, phase II clinical trial. BMJ Open. 2025 April 14; 15(04):e094386. doi: 10.1136/bmjopen-2024-094386. PMID: 40228859; PMCID: PMC11997836.
33. www.sleepfoundation.org/sleepdeprivation/lack-of-sleep-and-cognitive-impairment
34. https://www.cnsvs.com
35. Bodenheimer, T. 2000. Uneasy alliance: Clinical investigators and the pharmaceutical industry. New England Journal of Medicine 342:1539-1544.
36. https://www.nytimes.com/2022/09/15/health/fda-drug-industry-fees.html
37. J. Bradford Rice, Urvi Desai, Alice Kate G. Cummings, Howard G. Birnbaum, Michelle Skornicki, Nathan B. Parsons; Burden of Diabetic Foot Ulcers for Medicare and Private Insurers. Diabetes Care 1 March 2014; 37 (3): 651–658. https://doi.org/10.2337/dc13-2176
38. Ford ND, Slaughter D, Edwards D, et al. Long COVID and Significant Activity Limitation Among Adults, by Age — United States, June 1–13, 2022, to June 7–19, 2023. MMWR Morb Mortal Wkly Rep 2023;72:866–870.
39. Gelly HB. Trends in Medicare costs of hyperbaric oxygen therapy, 2013 through 2022. Undersea Hyperb Med. 2024;51(2):137–144. Published June 2024. Accessed June 24, 2025.