Fatigue and cognitive impairment remain among the most stubborn symptoms of Long COVID, affecting millions worldwide months or even years after their initial SARS-CoV-2 infection. While treatment options have remained limited, a new prospective observational study from South Korea offers a carefully documented signal that hyperbaric oxygen therapy (HBOT) may provide meaningful relief.
Published in the Journal of Korean Medical Science on July 13, 2026, the study followed 49 Long COVID patients with clinically significant fatigue through a structured HBOT protocol. The results suggest that a relatively short course of treatment—just 10 sessions—was associated with substantial improvements not only in fatigue but also in verbal memory, working memory, and overall mental health outcomes.
Study Design and Patient Population
The research team at Myongji Hospital and Hanyang University College of Medicine recruited adults aged 20–69 who had confirmed COVID-19 at least 12 weeks prior and reported persistent fatigue that began within six months of their initial infection. All participants scored 4 or higher on the Chalder Fatigue Scale, indicating fatigue “caseness”—a threshold associated with meaningful functional impairment.
This single-arm, prospective observational design represents a pragmatic approach to generating early efficacy signals in a condition where placebo-controlled trials are methodologically challenging. Participants served as their own controls, with pre- and post-treatment assessments separated by at least four weeks to minimize learning effects on neurocognitive testing.
The Treatment Protocol
Patients received 10 HBOT sessions delivered once daily on weekdays over approximately two weeks. Each session followed a standard clinical protocol: 90 minutes total at 2.0 atmospheres absolute, with participants breathing 100% oxygen in three 20-minute periods separated by two 5-minute air breaks. The 10-minute compression and decompression phases bracketed the therapeutic exposure.
This dosing schedule aligns with protocols used in previous Long COVID studies and is notably shorter than the 40-session regimens employed in some Israeli research. The investigators chose this approach to balance therapeutic potential against practical accessibility and patient burden.
Primary Outcome: Fatigue Recovery
The study’s primary endpoint was fatigue recovery, defined as achieving a Chalder Fatigue Scale bimodal score below 4—transitioning from “caseness” to non-clinical levels. Among the 49 participants who received at least one HBOT session, 36 (73.5%) met this criterion after completing treatment.
The magnitude of improvement was substantial. Mean fatigue severity scores on the Likert scale dropped from 22.67 at baseline to 6.46 post-treatment—a difference that was highly statistically significant. Even when researchers applied conservative assumptions for the 12 participants who did not complete all sessions, the effect remained robust.
Notably, seven of the 12 dropouts discontinued due to adverse events—primarily middle ear barotrauma during pressurization—while five withdrew consent. All barotrauma cases resolved fully without long-term complications, underscoring the importance of careful ear pressure equalization protocols and prompt otolaryngology consultation when symptoms arise.
Secondary Outcomes: Cognitive Function and Mental Health
Beyond fatigue, the study battery assessed four cognitive domains using validated neuropsychological instruments. Verbal memory and working memory showed statistically significant improvements after HBOT, with effect sizes suggesting clinical relevance. Attention, processing speed, and executive function measures trended toward improvement but did not reach statistical significance after correction for multiple comparisons.
Mental health outcomes told a similarly positive story. Scores on the Hospital Anxiety and Depression Scale improved significantly for both anxiety and depression subscales. Sleep quality, measured by the Pittsburgh Sleep Quality Index, and post-traumatic stress symptoms related to COVID-19 also showed meaningful reductions.
Perhaps most tellingly, participants reported fewer total Long COVID symptoms after treatment. The multidimensional impact of HBOT—spanning physical fatigue, cognitive function, and psychological well-being—suggests a systemic rather than purely symptomatic effect.
Mechanistic Context: Why HBOT for Long COVID?
The investigators frame their findings within an emerging mechanistic understanding of Long COVID pathophysiology. Multiple lines of evidence point to persistent systemic oxidative stress, mitochondrial dysfunction, and neuroinflammation as downstream pathways linking acute SARS-CoV-2 infection to chronic symptoms.
HBOT’s therapeutic rationale rests on several biologically plausible mechanisms. By delivering oxygen at increased partial pressures, the therapy enhances tissue oxygenation beyond what hemoglobin-bound transport can achieve—potentially reaching hypoxic tissue compartments. The treatment also modulates inflammatory cascades, promotes angiogenesis, and may improve mitochondrial energy metabolism. These effects have been documented in traumatic brain injury populations, where HBOT has shown neuroplasticity-inducing properties even years after initial injury.
The South Korean findings align with preliminary reports from other centers, including improvements in fatigue and cognitive function observed in Israeli and UK cohorts. However, the mixed results from the Swedish HOT-LoCO trial—where 10 sessions of HBOT showed no benefit over sham control—caution against overinterpreting single-arm data.
The FDA Position: Important Caveats
While the Korean study adds to a growing literature suggesting HBOT’s potential for Long COVID, regulatory authorities maintain a cautious stance. The U.S. Food and Drug Administration has not cleared or approved hyperbaric oxygen therapy for Long COVID, post-COVID conditions, or any post-viral fatigue syndrome.
The FDA’s consumer guidance explicitly lists conditions for which HBOT is not established as safe and effective, including chronic fatigue, brain fog, and post-viral syndromes. This regulatory position reflects the absence of large-scale randomized controlled trials with sham controls—studies that remain methodologically challenging given the sensory experience of HBOT pressurization.
Patients considering HBOT for Long COVID symptoms should understand that such use falls outside FDA-cleared indications. Treatment decisions should involve informed discussions with healthcare providers about the evidence base, potential risks including middle ear barotrauma and oxygen toxicity, and out-of-pocket costs, as insurance typically does not cover off-label applications.
Safety Considerations
The Korean study’s safety profile reinforces established HBOT risk parameters. Middle ear barotrauma occurred in approximately 14% of participants—consistent with rates reported in clinical populations. All cases resolved without sequelae, highlighting the importance of patient education about ear pressure equalization techniques and immediate reporting of discomfort during pressurization.
Contraindications to HBOT include untreated pneumothorax, certain chronic lung conditions, and some chemotherapy agents. The Myongji Hospital team appropriately excluded patients with these conditions, and their systematic adverse event monitoring provides a template for safe outpatient HBOT administration.
Implications for Clinical Practice and Research
This study contributes to an evolving evidence base that will require randomized sham-controlled trials to definitively establish HBOT’s efficacy for Long COVID. The 73% fatigue recovery rate and cognitive improvements observed are promising signals, but without a control group, placebo effects and natural symptom fluctuation cannot be excluded.
For clinicians, the findings suggest that HBOT may be a reasonable consideration for selected Long COVID patients with prominent fatigue and cognitive symptoms—particularly those who have not responded to conventional rehabilitation approaches. The 10-session protocol offers a relatively accessible entry point compared to more intensive regimens.
For researchers, the Korean team’s multidimensional outcome battery provides a model for comprehensive Long COVID trial design. The inclusion of objective neuropsychological testing alongside patient-reported outcomes strengthens the methodological rigor of future studies.
As the global Long COVID burden continues to affect quality of life for millions, rigorous investigation of promising therapies like HBOT remains essential. This South Korean contribution adds an important data point to an increasingly nuanced international conversation about hyperbaric oxygen’s potential role in post-viral recovery.