Long Covid

Written By Elizabeth Gaffney

Hyperbaric Oxygen Therapy for Long COVID-19

Introduction

Hyperbaric Oxygen Therapy (HBOT) consists of breathing oxygen at a pressure higher than local atmospheric pressure for multiple sessions for the treatment or prevention of specific diseases. As per the European Code of Good Practice (Kot et al.), there is a general consensus that the term HBOT can only be applied when the partial pressure of oxygen in breathing mixture exceeds 1.5 absolute atmosphere (ATA) for a minimum period of 60 minutes (excluding compression and decompression).

HBOT is a therapeutic option for post-acute sequelae of SARS-CoV-2 infection, or long COVID, which refers to symptoms that persist after the acute phase of COVID-19 infection has resolved. These symptoms include persistent fatigue, cognitive impairment, shortness of breath, chest pain, joint pain, and various neurological and psychological issues. The pathophysiology of long COVID is not fully understood, but HBOT offers a promising adjunctive treatment for long COVID, including enhanced oxygenation, reduced inflammation, improved neuroplasticity, and better mitochondrial function. Clinical evidence supports the potential benefits of HBOT in reducing symptoms and improving the quality of life for long COVID patients.

Mechanisms of Action of HBOT

During HBOT, patients are treated with pure oxygen in a chamber in which the pressure is higher than atmospheric pressure (2 ATA) for 1.5 hours for multiple sessions. HBOT may be beneficial in the treatment of long COVID via several mechanisms.

1. Enhanced oxygenation: The primary mechanism by which HBOT exerts its effects is through enhanced oxygenation of tissues (Cannellotto et al., 2024). This is particularly beneficial in patients suffering from hypoxia or impaired oxygen utilisation, which is observed in long COVID patients (Adingupu et al., 2023).

2. Reduction of inflammation: Persistent inflammation and immune dysregulation are hallmarks of long COVID (Talla et al., 2023). HBOT reduces the levels of pro-inflammatory cytokines and modulates the immune response (Cannellotto et al., 2024), which may help alleviate symptoms such as fatigue, pain, and cognitive impairment.

3. Angiogenesis and tissue repair: HBOT promotes the release of growth factors and stem cells, which support angiogenesis and tissue repair (De Wolde et al., 2021). Tissue damage and poor vascular function have been implicated in long COVID, and the increased oxygen enhances wound healing and regeneration of organs and tissues damaged by the virus (Pan et al., 2023).

4. Neuroplasticity and cognitive function: Cognitive impairment, or “brain fog”, is a debilitating symptom of long COVID. Hypoxic conditions in the brain may contribute to cognitive dysfunction in long COVID (Adingupu et al., 2023) and by improving oxygen delivery to the brain, HBOT may enhance neuroplasticity and reduce neuroinflammation (Wahl et al., 2019).

5. Mitochondrial function: Mitochondrial dysfunction is implicated in long COVID and HBOT enhances mitochondrial function by improving oxygen availability, boosting ATP production, and reducing oxidative damage, thereby increasing energy production and alleviating fatigue (Molnar et al., 2024).

 Benefits of HBOT for Patients with Long Covid

1. Symptom relief: The primary benefit of HBOT for long COVID patients is the potential for comprehensive symptom relief (Katz et al., 2024). By addressing underlying mechanisms, such as hypoxia, inflammation, and mitochondrial dysfunction, HBOT can alleviate a range of symptoms, including fatigue, cognitive impairment, shortness of breath, and pain.

2. Improved quality of life: HBOT can improve energy levels, reduce pain, and enhance the cognitive function of long COVID patients, thus contributing to a better ability to engage in daily tasks and social activities (Robbins et al., 2021).

3. Reduced medical burden: By providing effective symptom relief and improving overall health, HBOT may reduce the long-term medical burden associated with long COVID, including fewer doctor visits, reduced medication use, and less need for supportive therapies (Franjic, 2023).

Clinical Evidence Supporting HBOT for Long COVID

Despite a lack of standardised treatment protocols and limited large-scale studies, the current evidence, including controlled trials and meta-analyses, indicates that HBOT is beneficial for long COVID patients and may improve symptoms such as cognitive function and fatigue, thereby supporting recovery and improving patients’ quality of life.

1. Reviews and meta-analyses: Katz et al. (2024) reviewed 10 clinical trials and concluded that HBOT (100% O2, 2–2.5 ATA, 75–105 mins, 10–60 sessions) effectively addresses the pathophysiology of long COVID. A systematic review of 10 studies by Wu et al. (2024) found that HBOT (typically 100% O2, 2 ATA, 90 mins, 40 daily sessions) can improve quality of life, fatigue, cognition, neuropsychiatric symptoms, and cardiopulmonary function of long COVID patients.

2. Randomised controlled trials: HBOT has a favourable safety profile for the treatment of long COVID patients (Kjellberg et al., 2023). An RCT by Zilberman-Itskovich et al. (2022) found that HBOT (100% O2, 2 ATA, 90 mins, 40 sessions) induces neuroplasticity and improves cognitive function and psychiatric symptoms and decreases fatigue, sleep disturbance and pain of long COVID patients. Longitudinal follow-up of the same trial showed that the clinical improvements persist for at least a year after the final HBOT session (Hadanny et al., 2024).

3. Pilot studies and case reports: Many pilot studies and case reports have shown the benefits of HBOT (100% O2, 2–2.5 ATA, 75–90 mins, 10–60 sessions) for long COVID patients, including improvements in cognition and cardiopulmonary function (Robbins et al., 2021; Bhaiyat et al., 2022; Kitala et al., 2022), as well as pain and emotional wellbeing (Lindenmann et al., 2023; Zant et al., 2022). A small study showed that HBOT (100% O2, 2.4 ATA, 90 mins, 15 sessions) attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammatory biomarkers in long COVID patients (Mrakic-Sposta et al., 2023).

4. Neuroimaging studies: A randomised sham-controlled trial using pre- and post-treatment fMRI and diffusion tensor imaging found that HBOT (100% O2, 2 ATA, 90 mins, 40 sessions) improves disruptions in white matter tracts and alters the functional connectivity organisation of neural pathways attributed to cognitive and emotional recovery in post-COVID-19 patients (Catalogna et al., 2022).

 Conclusion

By addressing multiple underlying mechanisms, HBOT offers a promising adjunctive treatment for long COVID via enhanced oxygenation, reduced inflammation, improved neuroplasticity, and better mitochondrial function. Clinical evidence, including randomised controlled trials, pilot studies, neuroimaging research, and case reports, supports the potential benefits of HBOT in reducing symptoms and improving quality of life for long COVID patients.

References

  • Adingupu, D. D., Soroush, A., Hansen, A., Twomey, R., & Dunn, J. F. (2023). Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19. Journal of Neurology, 270(7), 3303–3314.

  • Bhaiyat, A. M., Sasson, E., Wang, Z., Khairy, S., Ginzarly, M., Qureshi, U., … & Efrati, S. (2022). Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. Journal of Medical Case Reports, 16(1), 80.

  • Cannellotto, M., Yasells García, A., & Landa, M. S. (2024). Hyperoxia: Effective mechanism of hyperbaric treatment at mild-pressure. International Journal of Molecular Sciences, 25(2), 777.

  • Catalogna, M., Sasson, E., Hadanny, A., Parag, Y., Zilberman-Itskovich, S., & Efrati, S. (2022). Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial. NeuroImage: Clinical, 36, 103218.

  • De Wolde, S. D., Hulskes, R. H., Weenink, R. P., Hollmann, M. W., & Van Hulst, R. A. (2021). The effects of hyperbaric oxygenation on oxidative stress, inflammation and angiogenesis. Biomolecules, 11(8), 1210.

  • Franjic, S. (2023). Hyperbaric oxygen therapy in the age of COVID-19. Journal of Nursing and Critical Care, 1(2)

  • Hadanny, A., Zilberman-Itskovich, S., Catalogna, M., Elman-Shina, K., Lang, E., Finci, S., … & Efrati, S. (2024). Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial. Scientific Reports, 14(1), 3604.

  • Katz, A. A., Wainwright, S., Kelly, M. P., Albert, P., & Byrne, R. (2024). Hyperbaric oxygen effectively addresses the pathophysiology of long COVID: Clinical review. Frontiers in Medicine, 11, 1354088.

  • Kitala, D., Łabuś, W., Kozielski, J., Strzelec, P., Nowak, M., Knefel, G., … & Kucharzewski, M. (2022). Preliminary research on the effect of hyperbaric oxygen therapy in patients with post-COVID-19 syndrome. Journal of Clinical Medicine, 12(1), 308.

  • Kjellberg, A., Hassler, A., Boström, E., El Gharbi, S., Al-Ezerjawi, S., Kowalski, J., … & Lindholm, P. (2023). Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial. BMC Infectious Diseases, 23(1), 33.

  • Kot J, Desola J, Lind F, Mueller P, Jansen E, Burman F, Working Group WG. A European code of good practice for hyperbaric oxygen therapy – Review 2022. Diving Hyperb Med. 2023 Dec 20;53(4)(Suppl) :1-17.

  • Lindenmann, J., Porubsky, C., Okresa, L., Klemen, H., Mykoliuk, I., Roj, A., … & Smolle-Juettner, F. M. (2023). Immediate and long-term effects of hyperbaric oxygenation in patients with long COVID-19 syndrome using SF-36 survey and VAS score: A clinical pilot study. Journal of Clinical Medicine, 12(19), 6253.

  • Molnar, T., Lehoczki, A., Fekete, M., Varnai, R., Zavori, L., Erdo-Bonyar, S., … & Ezer, E. (2024). Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches. GeroScience, 1–20.

  • Mrakic-Sposta, S., Vezzoli, A., Garetto, G., Paganini, M., Camporesi, E., Giacon, T. A., … & Bosco, G. (2023). Hyperbaric oxygen therapy counters oxidative stress/inflammation-driven symptoms in long COVID-19 patients: preliminary outcomes. Metabolites, 13(10), 1032.

  • Pan, J. Q., Tian, Z. M., & Xue, L. B. (2023). Hyperbaric oxygen treatment for long covid: From molecular mechanism to clinical practice. Current Medical Science, 43(6), 1061–1065.

  • Robbins, T., Gonevski, M., Clark, C., Baitule, S., Sharma, K., Magar, A., … & Randeva, H. S. (2021). Hyperbaric oxygen therapy for the treatment of long COVID: Early evaluation of a highly promising intervention. Clinical Medicine, 21(6), e629–e632.

  • Talla, A., Vasaikar, S. V., Szeto, G. L., Lemos, M. P., Czartoski, J. L., MacMillan, H., … & Torgerson, T. R. (2023). Persistent serum protein signatures define an inflammatory subcategory of long COVID. Nature Communications, 14(1), 3417.

  • Wahl, A. M., Bidstrup, D., Smidt-Nielsen, I. G., Werner, M. U., Hyldegaard, O., & Rotbøll-Nielsen, P. (2019). A single session of hyperbaric oxygen therapy demonstrates acute and long-lasting neuroplasticity effects in humans: A replicated, randomized controlled clinical trial. Journal of Pain Research, 12, 2337–2348.

  • Wu, B. Q., Liu, D. Y., Shen, T. C., Lai, Y. R., Yu, T. L., Hsu, H. L., … & Hsia, T. C. (2024). Effects of hyperbaric oxygen therapy on long COVID: A systematic review. Life, 14(4), 438.

  • Zant, A. E., Figueroa, X. A., Paulson, C. P., & Wright, J. K. (2022). Hyperbaric oxygen therapy to treat lingering COVID-19 symptoms. Undersea & Hyperbaric Medicine, 49(3).

  • Zilberman-Itskovich, S., Catalogna, M., Sasson, E., Elman-Shina, K., Hadanny, A., Lang, E., … & Efrati, S. (2022). Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: Randomized controlled trial. Scientific Reports, 12(1), 11252.

Elizabeth Gaffney https://www.sourceprojects.co
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