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

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.

Source: Pan JQ, Tian ZM, Xue LB. Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice. Curr Med Sci. 2023 Nov 4. doi: 10.1007/s11596-023-2799-1. Epub ahead of print. PMID: 37924387. https://pubmed.ncbi.nlm.nih.gov/37924387/

Hyperbaric oxygen treatment for long coronavirus disease-19: a case report

Abstract:

Background: The coronavirus disease 2019 pandemic has resulted in a growing population of individuals who experience a wide range of persistent symptoms referred to as “long COVID.” Symptoms include neurocognitive impairment and fatigue. Two potential mechanisms could be responsible for these long-term unremitting symptoms: hypercoagulability, which increases the risk of blood vessel occlusion, and an uncontrolled continuous inflammatory response. Currently, no known treatment is available for long COVID. One of the options to reverse hypoxia, reduce neuroinflammation, and induce neuroplasticity is hyperbaric oxygen therapy. In this article, we present the first case report of a previously healthy athletic individual who suffered from long COVID syndrome treated successfully with hyperbaric oxygen therapy.

Case presentation: A previously healthy 55-year-old Caucasian man presented 3 months after severe coronavirus disease 2019 infection with long COVID syndrome. His symptoms included a decline in memory, multitasking abilities, energy, breathing, and physical fitness. After evaluation that included brain perfusion magnetic resonance imaging, diffusion tensor imaging, computerized cognitive tests, and cardiopulmonary test, he was treated with hyperbaric oxygen therapy. Each session included exposure to 90 minutes of 100% oxygen at 2 atmosphere absolute pressure with 5-minute air breaks every 20 minutes for 60 sessions, 5 days per week. Evaluation after completing the treatment showed significant improvements in brain perfusion and microstructure by magnetic resonance imaging and significant improvement in memory with the most dominant effect being on nonverbal memory, executive functions, attention, information procession speed, cognitive flexibility, and multitasking. The improved cognitive functions correlated with the increased cerebral blood flow in brain regions as measured by perfusion magnetic resonance imaging. With regard to physical capacity, there was a 34% increase in the maximum rate of oxygen consumed during exercise and a 44% improvement in forced vital capacity. The improved physical measurements correlated with the regain of his pre-COVID physical capacity.

Conclusions: We report the first case of successfully treated long COVID symptoms with hyperbaric oxygen therapy with improvements in cognition and cardiopulmonary function. The beneficial effects of hyperbaric oxygen shed additional light on the pathophysiology of long COVID. As this is a single case report, further prospective randomized control studies are needed.

Source: 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848789/ (Full text)

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial

Abstract:

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection.

Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = – 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001).

Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate.

These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT’s beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

Source: Zilberman-Itskovich S, Catalogna M, Sasson E, Elman-Shina K, Hadanny A, Lang E, Finci S, Polak N, Fishlev G, Korin C, Shorer R, Parag Y, Sova M, Efrati S. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Sci Rep. 2022 Jul 12;12(1):11252. doi: 10.1038/s41598-022-15565-0. PMID: 35821512; PMCID: PMC9276805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276805/ (Full text)

Hyperbaric Oxygen for Treatment of Long COVID Syndrome (HOT-LoCO); Protocol for a Randomised, Placebo-Controlled, Double-Blind, Phase II Clinical Trial

Abstract:

Introduction: Long COVID, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, post-exertional malaise, and cognitive dysfunction. There is currently no effective treatment, and the underlying mechanisms are unknown although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in Long COVID. This randomised placebo-controlled clinical trial will explore HBOT as a potential treatment for Long COVID.

The primary objective is to evaluate if HBOT improves health related quality of life (HRQoL) for patients with Long COVID compared to placebo/sham. The main secondary objectives are to evaluate whether HBOT improves endothelial function, objective physical performance, and short term HRQoL.

Methods and Analysis: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to Long COVID, with low HRQoL. Clinical data, HRQoL-questionnaires, blood samples, objective tests and activity meter data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over six weeks. Assessments for safety and efficacy will be performed at six, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND-36) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent Data Safety Monitoring Board.

Ethics and Dissemination: The trial is approved by The Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Product Agency (5.1-2020-36673). Positive, negative, and inconclusive results will be published in peer-reviewed scientific journals with open access.

Trial Registration NCT04842448. EudraCT: 2021-000764-30 Strengths and limitations of this trial Strengths -Randomised placebo-controlled, double-blind, parallel groups, clinical trial in compliance with ICH-GCP -Evaluation of safety and efficacy, including objective and explanatory endpoints -Independent Data Safety Monitoring Board (DSMB) Limitations -New syndrome with unknown mechanisms -Power calculation is based on similar syndromes -Selection bias as patients are enrolled from the same post-COVID clinic

Source: Anders KjellbergLina Abdel-HalimAdrian HasslerSara El GharbiSarah Al-EzerjawiEmil BoströmCarl Johan SundbergJohn PernowKoshiar MedsonJan KowalskiKenny A Rodriguez-WallbergXiaowei ZhengSergiu Bogdan CatrinaMichael RunoldMarcus StåhlbergJudith BruchfeldMalin Nygren-BonnierPeter Lindholm. Hyperbaric Oxygen for Treatment of Long COVID Syndrome (HOT-LoCO); Protocol for a Randomised, Placebo-Controlled, Double-Blind, Phase II Clinical Trial.

Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention

Abstract:

Background: Long COVID is a common occurrence following COVID-19 infection. The most common symptom reported is fatigue. Limited interventional treatment options exist. We report the first evaluation of hyperbaric oxygen therapy (HBOT) for long COVID treatment.

Methods: A total of 10 consecutive patients received 10 sessions of HBOT to 2.4 atmospheres over 12 days. Each treatment session lasted 105 minutes, consisting of three 30-minute exposures to 100% oxygen, interspersed with 5-minute air breaks. Validated fatigue and cognitive scoring assessments were performed at day 1 and 10. Statistical analysis was with Wilcoxon signed-rank testing reported alongside effect sizes.

Results: HBOT yielded a statistically significant improvement in the Chalder fatigue scale (p=0.0059; d=1.75 (very large)), global cognition (p=0.0137; d=-1.07 (large)), executive function (p=0.0039; d=-1.06 (large)), attention (p=0.0020; d=-1.2 (very large)), information processing (p=0.0059; d=-1.25 (very large)) and verbal function (p=0.0098; d=-0.92 (large)).

Conclusion: Long COVID-related fatigue can be debilitating, and may affect young people who were previously in economic employment. The results presented here suggest potential benefits of HBOT, with statistically significant results following 10 sessions.

Source: Robbins T, Gonevski M, Clark C, Baitule S, Sharma K, Magar A, Patel K, Sankar S, Kyrou I, Ali A, Randeva HS. Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention. Clin Med (Lond). 2021 Nov;21(6):e629-e632. doi: 10.7861/clinmed.2021-0462. PMID: 34862223. https://www.rcpjournals.org/content/clinmedicine/21/6/e629 (Full text)

The efficacy of hyperbaric oxygen therapy in the management of chronic fatigue syndrome

Erratum in: Undersea Hyperb Med. 2013 May-Jun;40(3):312.

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is a chronic disease with social components that ensue secondary to the incapacity of the person to fulfill work, social and family responsibilities. Currently, there is no consensus regarding its treatment. The aim of this study was to determine the efficacy of hyperbaric oxygen (HBO2) therapy in CFS.

DESIGN: Sixteen patients included in the study were diagnosed with CFS according to the Fukuda criteria. Patients received 15 treatment sessions of HBO2 therapy over a period of three consecutive weeks (five days per week). The outcome measures (visual analog fatigue scale (VAFS). Fatigue Severity Scale (FSS) and Fatigue Quality of Life Score (FQLS) were assessed before the treatment and after completion of the 15 sessions.

RESULTS: HBO2 therapy was well tolerated, with no complications. After treatment, patients’ scores were found to have improved with respect to VAFS, FSS and FQLS (all p<0.005).

CONCLUSIONS: We may infer that HBO2 therapy decreases the severity of symptoms and increases the life quality of CFS patients. It may be a new treatment modality for the management of CFS. However, further studies with larger sample sizes and control groups are definitely awaited.

Source: Akarsu S, Tekin L, Ay H, Carli AB, Tok F, Simşek K, Kiralp MZ. The efficacy of hyperbaric oxygen therapy in the management of chronic fatigue syndrome. Undersea Hyperb Med. 2013 Mar-Apr;40(2):197-200. https://www.ncbi.nlm.nih.gov/pubmed/23682549

 

The diagnosis of postviral syndrome

Note: This comment appeared in Journal of the Royal Society of Medicine Volume 83 June 1990. You can view the table referenced in the comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292703/pdf/jrsocmed00135-0083a.pdf

 

The difficulty of making a definitive diagnosis of postviral syndrome (myalgic encephalomyelitis) is emphasized by Dr Bowman and his colleagues (December 1988 JRSM, p 712).

After a patient with this condition reported benefit from hyperbaric oxygen (HBO) (1), 36 other patients requested to be treated at Centres administered by ‘Action and Research for Multiple Sclerosis’ (ARMS). Thirty had been investigated in hospital.

They received 20 daily one hour sessions breathing 100% oxygen under pressure. Thirteen patients reported symptomatic improvement at 1.25 atmospheres absolute (ata), 10 responded at 1.5 ata, three at 1.75 ata and two at 2.0 ata.

The patients were asked to record any changes in their symptoms at the end of the course and their accumulated replies are given in Table 1.

A speculative explanation is that high concentrations of oxygen may limit the excessive intracellular lactic acid in skeletal muscle that has been demonstrated in this disease(2). The clinical pattern of myalgic encephalomyelitis has much in common with multiple sclerosis and it is possible that some of these patients had, in fact, got MS.

However, muscle pains are seldom a feature of MS, while they occurred in all but four of these patients. Seventeen out of the 33 with this symptom reported improvement, a response to HBO which might be elaborated into a therapeutic test.

ARMS treated these patients (with the consent of their doctors) on an empirical basis, and it is not implied that HBO is a definitive treatment for ME. However, these reports of subjective improvement suggest that a formal trial should be initiated.

~D J D PERRINS Adviser on Hyperbaric Medicine to ARMS, 4a Chapel Hill, Stansted, Essex CM24 8AG

 References

1 Newsletter of the M.E. Association No 21, 1986

2 Arnold DL, Bore PJ, Radda GK, et al. Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. Lancet 1984;i:1367-9

 

Source: D J Perrins. The diagnosis of postviral syndrome.  J R Soc Med. 1990 Jun; 83(6): 413. PMCID: PMC1292703  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292703/