Hyperbaric Oxygen Therapy for Long COVID: Current Insights

Researchers are exploring treatments for Long COVID, where symptoms persist for weeks or months after the initial infection. Among these, hyperbaric oxygen therapy (HBOT) has gained attention for its potential effects on inflammation, tissue repair, and oxygen delivery. Traditionally used for decompression sickness and wound healing, HBOT is now being studied for its impact on post-viral symptoms.

Examining its potential benefits requires a closer look at treatment protocols, physiological mechanisms, and emerging research on its role in addressing persistent fatigue and cognitive dysfunction.

Chamber Setup And Pressure Levels

Hyperbaric oxygen therapy for Long COVID is administered in specialized chambers that increase atmospheric pressure while delivering high concentrations of oxygen. These chambers come in two forms: monoplace, which accommodates a single individual and is typically made of clear acrylic, and multiplace, which can treat multiple patients simultaneously and requires oxygen masks or hoods. The choice depends on treatment protocols, facility resources, and patient needs.

Pressure levels are a key aspect of HBOT, influencing oxygen absorption and physiological responses. Standard protocols for conditions like decompression sickness use pressures between 2.0 and 3.0 atmospheres absolute (ATA). For Long COVID, studies have explored lower pressures, typically 1.3 to 2.0 ATA, which enhance oxygen diffusion while minimizing risks like barotrauma or oxidative stress. A 2022 randomized controlled trial in Scientific Reports found that HBOT at 2.0 ATA improved cognitive function and fatigue compared to a control group receiving sham treatments at 1.0 ATA.

Each HBOT session lasts between 60 and 90 minutes, with patients breathing nearly 100% oxygen intermittently to prevent oxygen toxicity. The pressurization phase takes 10 to 15 minutes, during which patients may experience mild ear discomfort due to middle ear pressure changes. To mitigate this, they are instructed to swallow or yawn. Once the target pressure is reached, oxygen is delivered continuously or in cycles, depending on the protocol. Depressurization is gradual to prevent decompression sickness, a concern at higher pressures.

Mechanisms Of Elevated Oxygen Concentration

HBOT increases oxygen availability by using elevated atmospheric pressure to dissolve more oxygen into plasma, bypassing the usual reliance on hemoglobin-bound transport. Under normal conditions, oxygen primarily binds to hemoglobin, with only a small fraction dissolving into plasma. Increased pressure significantly raises oxygen solubility in bodily fluids, allowing it to reach tissues with limited blood supply or compromised circulation.

Beyond diffusion, elevated oxygen concentration enhances mitochondrial function and cellular metabolism. Under pressures of 1.3 to 2.0 ATA, oxygen penetrates deeper into hypoxic tissues, supporting mitochondrial oxidative phosphorylation—the process responsible for generating adenosine triphosphate (ATP). In post-viral syndromes, mitochondrial efficiency may be impaired, reducing energy production. Increased oxygen availability may help restore ATP synthesis, improving energy-dependent processes.

Hyperoxia—an excess of oxygen in tissues—can temporarily elevate reactive oxygen species (ROS) production. While excessive ROS can contribute to oxidative stress, controlled increases serve as signaling molecules that activate protective pathways, such as angiogenesis and tissue remodeling. Research in Redox Biology (2021) highlights how hyperoxia-induced ROS stimulate hypoxia-inducible factors (HIFs), triggering adaptive responses that enhance oxygen utilization efficiency. This may improve vascular function and oxygen delivery even after therapy sessions conclude.

Links Between Prolonged Symptoms And Oxygen Deprivation

Persistent Long COVID symptoms have been linked to disruptions in oxygen delivery, contributing to fatigue, cognitive impairment, and autonomic dysfunction. One explanation involves microvascular dysfunction, where endothelial damage restricts oxygen flow to tissues. Functional MRI and transcranial Doppler ultrasound studies show reduced cerebral blood flow in some Long COVID patients, potentially causing brain fog and concentration difficulties. Insufficient oxygen supply to neural tissues can impair synaptic transmission and neurotransmitter recycling, leading to cognitive sluggishness.

Oxygen deprivation also affects muscle function and metabolism. Many Long COVID patients experience post-exertional malaise, where mild activity triggers excessive fatigue. Research suggests mitochondrial dysfunction plays a role, as impaired oxygen utilization forces muscle cells to rely more on anaerobic metabolism, leading to lactate accumulation. Exercise studies show Long COVID patients have abnormal lactate thresholds compared to healthy individuals. Reduced muscular oxygen availability limits endurance and contributes to widespread pain and delayed recovery.

Cardiopulmonary complications further disrupt oxygen transport. Some patients experience persistent shortness of breath despite normal lung imaging, suggesting a mismatch between oxygen demand and delivery. Pulmonary function tests reveal abnormalities such as reduced diffusion capacity, indicating impaired gas exchange. Dysautonomia, a common issue in Long COVID, can cause heart rate and blood pressure fluctuations that affect oxygen distribution. In postural orthostatic tachycardia syndrome (POTS), blood pooling in the lower extremities reduces cerebral perfusion upon standing, worsening dizziness and fatigue.

Session Frequency And Duration Approaches

Optimizing HBOT frequency and duration for Long COVID requires balancing therapeutic benefits with patient tolerance. Traditional protocols for conditions like chronic wounds or decompression sickness involve daily sessions over several weeks. For post-viral fatigue, studies have explored varied treatment schedules to sustain improvements while minimizing risks from prolonged oxygen exposure.

Long COVID patients typically receive HBOT five days per week for 20 to 40 sessions. Each session lasts 60 to 90 minutes, with patients breathing nearly pure oxygen at pressures of 1.3 to 2.0 ATA. Cumulative exposure is thought to enhance neuroplasticity, vascular remodeling, and metabolic efficiency over time. A retrospective analysis in Frontiers in Neurology (2023) found that participants who completed at least 30 sessions at 2.0 ATA reported sustained reductions in fatigue and improved cognitive performance compared to those who discontinued therapy earlier.

Potential Biological Pathways Investigated In Relation To Post-Viral Fatigue

Long COVID fatigue has led researchers to examine biological pathways contributing to prolonged energy deficits and systemic dysfunction. Mitochondrial inefficiency, neurovascular dysregulation, and inflammation all intersect with oxygen availability and utilization. HBOT has been proposed as an intervention due to its effects on mitochondrial function, neuroinflammation, and vascular integrity.

Mitochondrial dysfunction is a central factor in post-viral fatigue. Long COVID patients exhibit impaired oxidative phosphorylation and reduced ATP production. Muscle biopsies and metabolomic analyses reveal abnormalities in mitochondrial respiration, including decreased activity of key enzymes in the electron transport chain. This forces cells to rely more on glycolysis, increasing lactate accumulation and early-onset fatigue. HBOT may enhance mitochondrial biogenesis by upregulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a key regulator of energy metabolism. Increased oxygen availability also supports more efficient ATP synthesis, potentially alleviating energy deficits.

Neurovascular dysfunction is another concern, as reduced cerebral perfusion and blood-brain barrier disruptions have been linked to cognitive fatigue and brain fog. Functional MRI studies show decreased oxygen extraction in certain brain regions of Long COVID patients, correlating with cognitive impairments. HBOT may counteract these deficits by promoting angiogenesis through vascular endothelial growth factor (VEGF) stimulation, improving oxygen delivery to hypoxic neural tissues. Hyperoxia-induced neovascularization has been observed in stroke recovery, suggesting a potential parallel for post-viral neurological dysfunction.

Inflammation also plays a role, with elevated pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) contributing to neuroinflammation and systemic fatigue. HBOT has demonstrated anti-inflammatory effects by modulating cytokine release and reducing oxidative stress, mechanisms that may help restore homeostasis in individuals experiencing prolonged post-viral symptoms.