Hyperbaric Oxygen Therapy for Long COVID: Evidence, Mechanisms and Clinical Perspective

Key Takeaways

• Post-COVID condition is a heterogeneous, multisystem disorder requiring individualized care ^{1 2 3}
• HBOT has biologically plausible effects on angiogenesis, neuroplasticity, modulation of inflammatory signalling, and mitochondrial function ^{4 5 6}
• Higher-dose protocols (≈30–40 sessions) may improve cognitive outcomes ⁴.
• Shorter regimens (~10 sessions) have not shown consistent benefit over placebo ^{7 8}.
• Evidence remains limited and heterogeneous ⁶.
• HBOT should be considered an investigational adjunct within supportive care ^{2 6}.

Quick Summary

Long COVID, also known as Post-COVID Conditions, refers to a wide range of symptoms that persist or emerge weeks to months after an initial COVID-19 infection ¹. For many people, recovery isn’t a straight path—symptoms can last for months or even years, often coming and going or changing in intensity ¹. One of the most common challenges is overwhelming fatigue, especially post-exertional malaise, where even minor physical or mental effort can trigger a setback ^{1 3}. People may also experience breathlessness, chest discomfort, or heart palpitations, alongside neurological issues often described as “brain fog,” which can affect memory, focus, and sleep ¹.

Beyond these, long COVID can impact mental health, leading to anxiety or depression, and may also involve sensory changes like loss of taste or smell, as well as digestive problems ¹. With over 200 reported symptoms ranging from mild to debilitating, the condition can significantly disrupt daily life and functioning ¹. As research continues, long COVID remains a complex and evolving health issue affecting millions worldwide ¹.

At present, there is no single consensus treatment for Post-COVID Conditions ². Management typically focuses on symptom-based care, rehabilitation, and gradual recovery strategies tailored to the individual ². Clinical guidelines continue to evolve, with most approaches emphasizing pacing, supportive therapies, and multidisciplinary care rather than a one-size-fits-all solution ^{2 3}.

One area of growing interest is Hyperbaric Oxygen Therapy as a supportive therapy ⁶. It has been proposed as an adjunctive option because of its potential to enhance tissue oxygenation, support vascular repair and neuroplasticity, and influence inflammatory and mitochondrial pathways that may be involved in long COVID ^{4 5 6}. Early research offers cautious optimism: a well-designed trial using 40 treatment sessions reported meaningful improvements, particularly in cognitive function ⁴. However, subsequent independent studies using shorter protocols (such as 10 sessions) did not demonstrate a clear overall benefit compared to placebo ^{7 8}. This difference highlights that shorter treatment courses may be insufficient to produce measurable effects, and that longer, more intensive protocols could be necessary to achieve meaningful clinical improvements ^{4 7 8}.

In the following section, we explore this evidence in more detail and examine what it may mean for practical care.

Care Strategy

HBOT Protocols Reported in Long COVID Studies and Clinical Practice

Protocols used in published studies and clinical settings have varied ^{4 9 8 10}. In some of the stronger long-COVID studies and reports, HBOT has been delivered using ^{4 9 10}:

• 30 to 40 sessions ^{4 9 10}
• around 90 minutes per session ^{4 9 10}
• pressures around 2.0 -2.4 ATA ^{4 9 8 10}
• up to 5 sessions per week, if tolerated ^{4 9 10}
• adjustments to the treatment schedule should be considered, with gradual or gentle increments, for patients with marked fatigue, post-exertional malaise (PEM), or travel intolerance ^{3 7 10}

These protocols are based on research settings and clinical practice reports. HBOT is not currently part of standard guideline-based treatment for long COVID and should be considered an adjunctive, investigational approach alongside conventional care ^{2 6}. There is currently no established consensus on optimal treatment protocols, and further research is needed to determine appropriate patient selection, dosing, and duration ^{2 6}.

Biological Rationale for HBOT in Long COVID

The rationale for Hyperbaric Oxygen Therapy in Post-COVID Conditions is grounded in biologically plausible mechanisms rather than speculation ^{4 5 6}. Long COVID has been associated with a range of overlapping processes, including immune dysregulation, endothelial dysfunction, microvascular abnormalities, persistent inflammation, and impaired cellular energy metabolism ^{1 6}. Together, these pathways are thought to contribute to common symptoms such as fatigue, cognitive dysfunction, and reduced exercise tolerance ^{1 6}.

HBOT increases the amount of oxygen dissolved in plasma and, when delivered over a series of treatments, has been shown in other clinical contexts to activate oxygen- and pressure-sensitive pathways ^{4 5 6}. These include processes linked to angiogenesis, neuroplasticity, modulation of inflammatory signalling, and mitochondrial function ^{4 5 6}. While direct evidence in long COVID is still emerging, these mechanisms offer a coherent biological rationale for its use—particularly in patients with features suggestive of impaired tissue oxygenation, vascular dysregulation, or cognitive involvement ^{4 5 6}.

At the same time, while these findings are encouraging, biological plausibility does not necessarily translate into proven clinical effectiveness ⁶. The current evidence remains limited and mixed, and further high-quality studies are needed to determine which patients are most likely to benefit, as well as the optimal treatment protocols ^{7 8 6}.

Hyperbaric Oxygen Therapy in Long COVID: What the Clinical Evidence Shows

Higher-Quality Randomised Evidence

Strongest positive trial (Israel, 2022) ⁴

• Sham-controlled randomised study with 73 patients
• Compared Hyperbaric Oxygen Therapy vs placebo
• Protocol: 40 daily sessions over 2 months

Key findings:

• Significant improvement in global cognitive function
• Benefits in attention and executive function
• Secondary improvements in energy, sleep, psychiatric symptoms, and pain interference ⁴

Imaging results:

• Improved brain perfusion
• Microstructural brain changes consistent with recovery

Additional analyses from the same trial cohort

• Changes in functional and structural brain connectivity linked to cognitive and emotional improvement ⁵
• Cardiac substudy showed improvement in left ventricular strain in patients with baseline impairment ⁹
• Important limitation: Findings come from the same trial programme (not independent replication) ^{4 5 9}

Supportive mechanistic and cardiac evidence (Nature, 2023 randomised trial) ⁹

• Double-blind, sham-controlled randomised trial (n = 60)
• Compared Hyperbaric Oxygen Therapy vs placebo
• Protocol: 40 treatment sessions over several weeks

Key findings:

• Significant improvement in cardiac function, measured by global longitudinal strain, in the HBOT group compared to placebo
• Suggests potential reversal of subtle (subclinical) left ventricular dysfunction following COVID-19

Why this matters:

• Cardiac strain abnormalities are increasingly recognised in Post-COVID Conditions, even in patients without overt heart disease
• Improvement in this parameter supports the idea that HBOT may influence underlying vascular and microcirculatory dysfunction
• Provides objective physiological evidence that complements reported improvements in cognition and fatigue

Important limitations:

• Conducted within the same broader research programme as earlier positive HBOT studies
• Findings have not yet been independently replicated
• Clinical significance (how this translates into long-term patient outcomes) remains uncertain

Independent trials with shorter protocols (2025)

Swedish HOT-LoCO Phase II trial ⁷

• 80 patients randomised
• Protocol: 10 HBOT sessions vs sham over 6 weeks

Results:

• Both groups improved
• No significant difference between HBOT and placebo in primary outcomes

Belgian double-blind placebo-controlled trial ⁸

• 101 patients randomised
• Protocol: 10 sessions across different oxygen and pressure settings

Results:

• No significant differences in symptoms, function, or cognitive performance
• Some improvement reported in placebo group

Overall interpretation:

• Longer protocols (e.g. 40 sessions) show encouraging results ⁴
• Shorter protocols (e.g. 10 sessions) have not demonstrated clear benefit ^{7 8}
• Suggests treatment dose and duration may be important factors ^{4 7 8}
• Further high-quality, independently replicated studies are needed ^{7 8 6}

Clinical takeaway: Longer, more intensive HBOT protocols may offer potential benefit—particularly for cognitive symptoms—but current evidence is mixed, and it should be considered a carefully selected adjunct rather than a standard treatment ^{4 7 8 6}.

Observational and Follow-Up Data 11

Long-term follow-up (2024, original 40-session cohort)

• Follow-up of patients who completed 40 sessions of Hyperbaric Oxygen Therapy
• Outcomes assessed approximately 1 year after treatment

Findings:

• Sustained improvements in quality of life
• Ongoing benefits in sleep, psychiatric symptoms, and pain

Key limitation:

• No long-term control comparison
• Most of the original sham group later received HBOT, limiting interpretation

Dutch prospective registry (2025, real-world data) 10

• 232 patients with Post-COVID Conditions
• Observational (non-randomised) registry study
• Outcomes assessed at 3 months using SF-36 scores

Findings:

• 56%–63% of patients showed clinically meaningful improvement in mental or physical health scores
• Greatest improvements seen in cognitive symptoms (e.g. concentration, processing, “brain fog”)

Important considerations:

• 13%–19% of patients experienced clinically relevant deterioration
• Observational design means causality cannot be established

Overall interpretation:

• Real-world data suggest that some patients may experience meaningful improvement, particularly in cognitive symptoms
• However, responses are variable, and findings should be interpreted cautiously due to lack of controlled comparison

Clinical takeaway: Observational data suggest that selected patients may benefit from Hyperbaric Oxygen Therapy—particularly for cognitive symptoms—but responses are variable ¹⁰. This likely reflects differences in underlying biology, including the degree of vascular dysfunction, inflammation, or mitochondrial impairment, as well as variation in symptom profiles, illness duration, and treatment protocols ^{10 6}.

What Systematic Reviews Say

HBOT-specific systematic review (2024)

Focused on Hyperbaric Oxygen Therapy in Post-COVID Conditions ⁶

Findings: Most studies reported improvements in:

• Quality of life
• Fatigue
• Cognitive function
• Neuropsychiatric symptoms
• Cardiopulmonary function

Key limitations:

• Small sample size
• Heterogeneous study designs
• Lack of large, high-quality randomized trials
• Variability in HBOT protocols (pressure, duration, number of sessions)

Overall interpretation:

• HBOT shows promising potential for improving long COVID symptoms, especially in fatigue and cognitive dysfunction
• However, evidence is still preliminary and more large-scale, well-designed RCTs are needed

Clinical takeaway: Systematic reviews indicate that while HBOT shows early promise, the evidence is not yet strong or consistent enough to support routine use, and it should be considered alongside better-established rehabilitation approaches.

Why the Evidence Is Still Evolving

Long COVID is a difficult field in which to run perfect randomised controlled trials ⁶. The condition is biologically heterogeneous, symptoms fluctuate, sham responses can be substantial, and the treatment itself is demanding ^{7 8 10 6}. In the Swedish HOT-LoCO study, investigators noted that many participants with severe fatigue and post-exertional malaise could not cope with treatment on consecutive days ⁷. In the Belgian trial, some patients could not proceed because of time constraints or logistical difficulties ⁸. In the Dutch registry, 10 patients stopped early because HBOT was too exhausting or worsened fatigue or other long-COVID symptoms ¹⁰.

That does not lower the standard of evidence required ⁶. But it does help explain why this area is slow to resolve, and why dose, pacing, patient selection, and phenotype may matter more here than in simpler conditions ^{7 8 10 6}.

Current Medical Perspective

The fairest reading of the literature is that HBOT for long COVID is promising, but not yet established ⁶. It should not be marketed as a guaranteed treatment, and it is not currently part of mainstream guideline-based standard care ^{2 6}. At the same time, the field should not be dismissed outright ^{4 5 9 10 6}. There is a credible physiological rationale, one well-designed sham-controlled positive trial using 40 sessions, supportive imaging and cardiac data, and growing real-world experience suggesting benefit in some patients, particularly those with prominent cognitive symptoms ^{4 5 9 10}.

Safety and Side Effects of HBOT

When delivered in an appropriate medical setting with proper screening and supervision, Hyperbaric Oxygen Therapy is generally well tolerated ^{4 7 8 10 6}. Reported side effects in Post-COVID Conditions studies are usually mild and temporary, including ear discomfort or barotrauma, fatigue during treatment, transient visual changes, anxiety or claustrophobia, cough, and chest discomfort ^{4 7 8 10 6}.

Occasional more significant events have been reported in the literature, such as a single treatment-related seizure in one trial; however, these are rare, typically reversible, and occur in controlled settings where patients are closely monitored ⁶. Some patients may also choose to pause or stop treatment if symptoms such as fatigue temporarily worsen ^{7 8 10}.

For these reasons, HBOT is best delivered under appropriate medical supervision, with careful screening and clear communication ⁶. Treatment should be individualised, with adjustments made as needed throughout the course, under the guidance of an experienced clinician ^{2 3 6}.

Frequently Asked Questions

Can Hyperbaric Oxygen Therapy Help Long COVID?

HBOT should not currently be described as a cure ^{2 6}. The available evidence suggests it may help selected patients—particularly in areas such as cognitive symptoms and overall quality of life—but it remains an emerging treatment approach rather than an established standard of care ^{4 11 10 6}.

How Many Hyperbaric Oxygen Therapy Sessions Are Used for Long COVID in Research?

There is currently no standardized protocol for Hyperbaric Oxygen Therapy (HBOT) in post-COVID conditions ⁶. Evidence from the strongest sham-controlled trial indicates that 40 sessions delivered over two months are associated with improvements across multiple outcomes ⁴.

Across published studies and clinical reports, treatment courses most commonly range from 30 to 40 sessions ^{4 9 10}. Shorter regimens appear insufficient to detect meaningful effects, likely due to the gradual and fluctuating course of long COVID symptoms ^{7 8}. Consistent with this, protocols of approximately 10 sessions have not demonstrated reliable benefits over placebo in recent trials ^{7 8}.

Which symptoms of long COVID respond most to Hyperbaric Oxygen Therapy (HBOT)?

Current evidence suggests the strongest signal is in cognitive symptoms, including brain fog, reduced concentration, attention difficulties, and mental fatigue ^{4 5 10 6}. Some studies and patient reports also note improvements in sleep, pain, energy levels, and overall function ^{4 11 10 6}.

Is Hyperbaric Oxygen Therapy (HBOT) a standard treatment for long COVID?

No. HBOT remains an off-label intervention and is not part of routine guideline-based care for long COVID ^{2 6}. Current recommendations focus on assessment, symptom management, self-management support, and multidisciplinary rehabilitation ^{2 3}.

References