Long COVID Symptoms and HBOT Research: A Detailed Look

Important: HBOT for long COVID is investigational. It is not FDA-approved for this use. Insurance will not cover it. Evidence is based on early trials and hasn’t been replicated at scale. Costs run $10,000-18,000 out-of-pocket for a 40-session protocol ($250-450 per session).

Long COVID is a multi-system syndrome with a poorly understood biology. HBOT research in this area is newer and more specific than many people realize. Here’s what the trials actually found and what they didn’t.

What Long COVID Actually Is

Long COVID isn’t one thing. It’s a syndrome — a collection of symptoms that cluster together in people who haven’t returned to baseline after COVID infection. The WHO defines it as symptoms persisting or beginning more than 4 weeks after COVID infection, lasting at least 2 months, not explained by another diagnosis.

The major symptom categories:

Cognitive dysfunction covers brain fog, memory impairment, word-finding difficulty, and slowed information processing. Many patients describe it as a mental cloudiness that makes routine tasks feel effortful.

Fatigue with post-exertional malaise (PEM) is the hallmark. PEM is not normal tiredness. It’s a disproportionate worsening of symptoms — cognitive, physical, or both — triggered by activity, lasting hours to days after exertion. PEM is what separates long COVID from simple deconditioning.

Autonomic dysfunction includes POTS (postural orthostatic tachycardia syndrome), heart rate spikes with standing, lightheadedness, and altered heart rate variability.

Respiratory symptoms including breathlessness disproportionate to exertion, persistent cough, and chest tightness.

Neurological symptoms beyond cognitive: headache, sensory disturbances, sleep disruption, and in some patients, peripheral neuropathy.

Not every long COVID patient has all of these. But cognitive dysfunction and fatigue are the most common.

What HBOT Research Is Targeting

The interest in HBOT for long COVID isn’t based on a general “oxygen is good” idea. Researchers have identified specific mechanisms that HBOT plausibly addresses:

Microclotting and vascular dysfunction: studies by Pretorius and colleagues found persistent microclots in long COVID patients’ blood that don’t break down normally. These microclots may impair blood flow in capillaries, reducing oxygen delivery to tissues including the brain. HBOT increases dissolved oxygen in plasma, which can reach tissues even through capillaries obstructed by microclots.

Neuroinflammation: imaging studies have found ongoing inflammation in brain tissue in long COVID patients. HBOT has anti-inflammatory effects and has been shown to reduce neuroinflammatory markers.

Mitochondrial dysfunction: some research suggests long COVID disrupts mitochondrial energy metabolism. HBOT supports mitochondrial function at the cellular level.

The Efrati 2022 Trial: What It Found

Efrati et al. (2022), published in Nature Communications, is the most rigorous trial to date. PMID: 36329021.

73 patients with long COVID were randomized to 40 HBOT sessions at 2.0 ATA (100% oxygen, 90 minutes per session) or a sham treatment. The sham used slightly higher than ambient pressure with room air — a common but imperfect control in hyperbaric research.

The HBOT group showed:

• Significant improvements in cognitive function across multiple domains: attention, memory, and information processing speed
• Reduced fatigue scores on validated scales
• Improved global quality of life metrics
• Increased regional cerebral blood flow on SPECT imaging
• Improved global brain connectivity on fMRI

These are meaningful findings from a well-designed trial. The sample size is modest. The sham condition in hyperbaric research is inherently imperfect (participants can often tell whether they’re in the real or sham group, introducing bias). But the imaging findings — objective, not just self-reported — add weight to the results.

The 2024 Follow-Up Data

Efrati’s group published follow-up data in Scientific Reports (2024) with longer-term outcomes from their long COVID HBOT work. Cognitive and functional improvements from the 40-session protocol were maintained at one year after treatment ended.

One-year durability is a meaningful finding if replicated. Many interventions show early benefit that fades.

What the Research Doesn’t Tell Us

Several important questions remain unanswered:

Who responds? The trials show group-level averages. Individual variation is high. Which patients respond, which don’t, and what predicts response hasn’t been established.

What’s the optimal protocol? 40 sessions at 2.0 ATA is what these trials used. Whether different pressures, durations, or session counts would be more or less effective isn’t known.

How does it compare to other treatments? There are no head-to-head trials comparing HBOT to other long COVID interventions.

Is it generalizable? The Efrati trials were conducted at Israeli centers with selected patient populations. Whether results hold across broader populations hasn’t been tested.

Cost and Access

A 40-session HBOT protocol runs approximately 8 weeks at 5 days/week. At $250-450 per session, total cost is $10,000-18,000. Insurance won’t cover it.

Before committing to private-pay HBOT, search ClinicalTrials.gov for ongoing long COVID HBOT trials. Clinical trials provide access to the treatment at no cost while generating data the field needs. Search terms: “hyperbaric oxygen long COVID.”

If you pursue private-pay HBOT, use a clinic that follows established protocols — 40 sessions minimum, appropriate pressure, a hyperbaric physician overseeing treatment. Avoid clinics offering “HBOT lite” at low pressures with few sessions and no physician oversight.

FAQ

Q: Does HBOT help long COVID? The Efrati et al. (2022) RCT showed meaningful cognitive and functional improvements (PMID: 36329021). It’s investigational. Insurance won’t cover it. More replication is needed.

Q: How much does HBOT cost for long COVID? $10,000-18,000 for a 40-session protocol ($250-450/session). Insurance doesn’t cover it. Check ClinicalTrials.gov for trials offering free access.

Q: What did the Efrati trial find? Improved cognition, reduced fatigue, better quality of life, and objective imaging improvements in cerebral blood flow and brain connectivity after 40 sessions.

Q: Is it covered by insurance? No. Not FDA-approved for this use. Entirely out-of-pocket.

Related: Long COVID and HBOT | HBOT Clinical Trials | HBOT Cost Guide

Medical Disclaimer: This content is for informational purposes only and does not constitute medical advice. HBOT for long COVID is investigational and not FDA-approved. Insurance will not cover this use. Evidence is preliminary. Always consult your care team before pursuing HBOT for long COVID. This site does not establish a doctor-patient relationship.