Skip to main content
SpringerLink
Log in

Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice

  • Reviews
  • Published:
Current Medical Science Aims and scope Submit manuscript

Abstract

Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection, last for more than 2 months, and cannot be explained by other diagnoses. The most common symptoms include fatigue, dyspnea, coughing, and cognitive impairment. The mechanisms of long COVID are not fully understood, but several hypotheses have been put forth. These include coagulation and fibrosis pathway activation, inflammatory and autoimmune manifestations, persistent virus presence, and Epstein-Barr virus reactivation. Hyperbaric oxygen therapy (HBOT) is a therapeutic method in which a person inhales 100% oxygen under pressure greater than that of the atmosphere. HBOT has some therapeutic effects, including improvement of microcirculation, inhibition of cytokine release leading to a reduction in inflammatory responses, inhibition of autoimmune responses, and promotion of neurological repair. Several clinical trials have been carried out using HBOT to treat long COVID. The results suggest that HBOT helps to improve symptom severity, reduce symptom duration, and enhance patients’ quality of life. It is believed that HBOT is an effective option for patients with long COVID, which is worth actively promoting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ballering AV, van Zon SKR, Olde Hartman TC, et al. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet, 2022,400(10350):452–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ayoubkhani D, Bermingham C, Pouwels KB, et al. Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study. BMJ, 2022,377:e069676

    Article  PubMed  Google Scholar 

  3. Shah W, Hillman T, Playford ED, et al. Managing the long term effects of covid-19: summary of NICE, SIGN, and RCGP rapid guideline. BMJ, 2021,372:n136

    Article  PubMed  Google Scholar 

  4. O’Mahoney LL, Routen A, Gillies C, et al. The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis. EClinicalMedicine, 2023,55:101762

    Article  PubMed  Google Scholar 

  5. Wulf Hanson S, Abbafati C, Aerts JG, et al. Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021. JAMA, 2022,328(16):1604–1615

    Article  PubMed  PubMed Central  Google Scholar 

  6. Huang L, Li X, Gu X, et al. Health outcomes in people years after surviving hospitalisation with COVID-19: a longitudinal cohort study. Lancet Respir Med, 2022,10(9):863–876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat Med, 2022,28(11):2398–2405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Subramanian A, Nirantharakumar K, Hughes S, et al. Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med, 2022,28(8):1706–1714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Katsoularis I, Fonseca-Rodriguez O, Farrington P, et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ, 2022,377: e069590

    Article  PubMed  Google Scholar 

  10. Fogarty H, Townsend L, Morrin H, et al. Persistent endotheliopathy in the pathogenesis of long COVID syndrome. J Thromb Haemost, 2021,19(10):2546–2553

    Article  CAS  PubMed  Google Scholar 

  11. Fogarty H, Ward SE, Townsend L, et al. Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction. J Thromb Haemost, 2022,20(10):2429–2438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pretorius E, Venter C, Laubscher GJ, et al. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Cardiovasc Diabetol, 2022,21(1):148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Phetsouphanh C, Darley DR, Wilson DB, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol, 2022,23(2):210–216

    Article  CAS  PubMed  Google Scholar 

  14. Pascolini S, Vannini A, Deleonardi G, et al. COVID-19 and Immunological Dysregulation: Can Autoantibodies be Useful? Clin Transl Sci, 2021,14(2): 502–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang EY, Mao T, Klein J, et al. Diverse functional autoantibodies in patients with COVID-19. Nature, 2021,595(7866):283–288

    Article  CAS  PubMed  Google Scholar 

  16. Kovarik JJ, Bileck A, Hagn G, et al. A multi-omics based anti-inflammatory immune signature characterizes long COVID-19 syndrome. iScience, 2023,26(1):105717

    Article  CAS  PubMed  Google Scholar 

  17. Rhea EM, Logsdon AF, Hansen KM, et al. The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Nat Neurosci, 2021,24(3):368–378

    Article  CAS  PubMed  Google Scholar 

  18. Frere JJ, Serafini RA, Pryce KD, et al. SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery. Sci Transl Med, 2022,14(664):eabq3059

    Article  CAS  PubMed  Google Scholar 

  19. Soung AL, Vanderheiden A, Nordvig AS, et al. COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis. Brain, 2022,145(12): 4193–4201

    Article  PubMed  PubMed Central  Google Scholar 

  20. Solomon T. Neurological infection with SARS-CoV-2 - the story so far. Nat Rev Neurol, 2021,17(2):65–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Matschke J, Lutgehetmann M, Hagel C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol, 2020,19(11):919–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Stein SR, Ramelli SC, Grazioli A, et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature, 2022,612(7941):758–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sun J, Xiao J, Sun R, et al. Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. Emerg Infect Dis, 2020,26(8):1834–1838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Vibholm LK, Nielsen SSF, Pahus MH, et al. SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses. EBioMedicine, 2021,64:103230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Peluso MJ, Deveau TM, Munter SE, et al. Chronic viral coinfections differentially affect the likelihood of developing long COVID. J Clin Invest, 2023,133(3): e163669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Godman CA, Chheda KP, Hightower LE, et al. Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells. Cell Stress Chaperones, 2010,15(4):431–442

    Article  CAS  PubMed  Google Scholar 

  27. Gregorevic P, Lynch GS, Williams DA. Hyperbaric oxygen modulates antioxidant enzyme activity in rat skeletal muscles. Eur J Appl Physiol, 2001,86(1):24–27

    Article  CAS  PubMed  Google Scholar 

  28. Benson RM, Minter LM, Osborne BA, et al. Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocytemacrophages. Clin Exp Immunol, 2003,134(1):57–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Moon BI, Kim HR, Choi EJ, et al. Attenuation of collagen-induced arthritis by hyperbaric oxygen therapy through altering immune balance in favor of regulatory T cells. Undersea Hyperb Med, 2017,44(4):321–330

    Article  PubMed  Google Scholar 

  30. Yang YJ, Wang XL, Yu XH, et al. Hyperbaric oxygen induces endogenous neural stem cells to proliferate and differentiate in hypoxic-ischemic brain damage in neonatal rats. Undersea Hyperb Med, 2008,35(2):113–129

    CAS  PubMed  Google Scholar 

  31. Gutsaeva DR, Suliman HB, Carraway MS, et al. Oxygen-induced mitochondrial biogenesis in the rat hippocampus. Neuroscience, 2006,137(2):493–504

    Article  CAS  PubMed  Google Scholar 

  32. Davis CH, Kim KY, Bushong EA, et al. Transcellular degradation of axonal mitochondria. Proc Natl Acad Sci USA, 2014,111(26):9633–9638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Paganini M, Bosco G, Perozzo FAG, et al. The Role of Hyperbaric Oxygen Treatment for COVID-19: A Review. Adv Exp Med Biol, 2021,1289:27–35

    Article  CAS  PubMed  Google Scholar 

  34. Sen S, Sen S. Therapeutic effects of hyperbaric oxygen: integrated review. Med Gas Res, 2021,11(1):30–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Harch PG. Hyperbaric oxygen treatment of novel coronavirus (COVID-19) respiratory failure. Med Gas Res, 2020,10(2):61–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 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

    Article  PubMed  Google Scholar 

  37. Catalogna M, Sasson E, Hadanny A, et al. Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial. Neuroimage Clin, 2022,36:103218

    Article  PubMed  PubMed Central  Google Scholar 

  38. 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(1):11252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zant AE, Figueroa XA, Paulson CP, et al. Hyperbaric oxygen therapy to treat lingering COVID-19 symptoms. Undersea Hyperb Med, 2022,49(3):333–339

    Article  PubMed  Google Scholar 

  40. 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

    Article  PubMed  Google Scholar 

  41. Nunn AVW, Guy GW, Brysch W, et al. Understanding Long COVID; Mitochondrial Health and Adaptation-Old Pathways, New Problems. Biomedicines, 2022,10 (12):3113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Schottlender N, Gottfried I, Ashery U. Hyperbaric Oxygen Treatment: Effects on Mitochondrial Function and Oxidative Stress. Biomolecules, 2021,11(12):1827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Liu Z, Kilic G, Li W, et al. Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19. Front Immunol, 2022, 13:838132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Balnis J, Madrid A, Hogan KJ, et al. Persistent blood DNA methylation changes one year after SARS-CoV-2 infection. Clin Epigenetics, 2022,14(1):94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cao X, Li W, Wang T, et al. Accelerated biological aging in COVID-19 patients. Nat Commun, 2022,13(1):2135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mongelli A, Barbi V, Gottardi Zamperla M, et al. Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors. Int J Mol Sci, 2021,22(11):6151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hachmo Y, Hadanny A, Abu Hamed R, et al. Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. Aging (Albany NY), 2020,12(22):22445–22456

    CAS  PubMed  Google Scholar 

  48. Liu K, Wu H, Gao R, et al. DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1. Pain Res Manag, 2020,2020:1528362

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kjellberg A, Hassler A, Boström E, et al. Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial. BMC Infect Dis, 2023,23(1):33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Leitman M, Fuchs S, Tyomkin V, et al. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

We thank Analisa Avila, Master of Public Health, Editor in the Life Sciences of Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the language of a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Hyperbaric Oxygen, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China

    Jian-qing Pan & Lian-bi Xue

  2. BGI-Shenzhen, Shenzhen, 518083, China

    Zhi-min Tian

Authors
  1. Jian-qing Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi-min Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lian-bi Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian-qing Pan.

Ethics declarations

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, Jq., Tian, Zm. & Xue, Lb. Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice. CURR MED SCI 43, 1061–1065 (2023). https://doi.org/10.1007/s11596-023-2799-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-023-2799-1

Key words

Search

Navigation