Back to Blog
Research & Clinical EvidenceHBOT-Series · 9 of 10

Hyperbaric Oxygen Therapy for Long COVID: What the Research Says in 2026

65 million people worldwide living with persistent symptoms — and what the emerging research examines

They did not die from their initial infection — but they have not fully recovered either. HBOT is one of several therapies being actively studied for long COVID; the research is promising but not yet conclusive, and HBOT is not FDA-cleared for this indication.

June 20, 2026

58%

Fatigue

44%

Brain fog

25%

Shortness of breath

22%

Chronic headache

Percentage of long COVID patients reporting each symptom — WHO 2024 data

Sixty-five million people worldwide are living with long COVID. They did not die from their initial infection — but they have not fully recovered either. Months or years after the acute illness resolved, they continue to experience fatigue so severe it disrupts daily life, brain fog that impairs work and concentration, shortness of breath on minimal exertion, and a constellation of symptoms that standard medicine has struggled to explain and largely failed to treat.

For these patients and the physicians treating them, hyperbaric oxygen therapy is among the interventions being studied most actively — with a notably rigorous body of research behind it, including randomized controlled trials published in 2022 and follow-on studies through 2026. It is important to frame that evidence carefully: HBOT is not FDA-cleared for long COVID, the findings are investigational, and they do not yet establish it as a proven treatment.

This post covers what long COVID is, why standard treatments fall short, what HBOT does at the biological level, and what the current research actually shows.

What Is Long COVID and Why Standard Treatments Fall Short

Long COVID — formally designated as Post-Acute Sequelae of SARS-CoV-2 infection, or PASC — is defined as the persistence of symptoms for more than 12 weeks following acute COVID-19 infection, where those symptoms cannot be explained by an alternative diagnosis.

It is not a fringe condition. The WHO estimates that 10 to 20 percent of people who contract COVID-19 develop long COVID symptoms. At global infection scales, that represents tens of millions of affected individuals — including millions in the United States who remain symptomatic years after their initial infection.

The symptom picture is heterogeneous — it varies widely between patients — but several clusters appear consistently:

  • •Fatigue and post-exertional malaise — exhaustion disproportionate to activity level, often worsened by physical or cognitive exertion
  • •Cognitive impairment — memory problems, difficulty concentrating, slowed processing speed — commonly called brain fog
  • •Cardiopulmonary symptoms — persistent shortness of breath, heart palpitations, chest tightness
  • •Neurological symptoms — headaches, dizziness, sensory disturbances, sleep disruption
  • •Autonomic dysfunction — dysregulation of heart rate, blood pressure, and temperature control, particularly on standing

Standard treatment approaches — rest, graduated exercise, symptom management, psychological support — have provided limited relief for many patients. The reason is that these approaches address symptoms without reaching the underlying biological mechanisms that are sustaining them. Understanding those mechanisms is the key to understanding why HBOT is showing results.

The Biological Mechanisms Behind Long COVID

Research into the pathophysiology of long COVID has identified several overlapping mechanisms that explain why symptoms persist long after the virus has cleared.

Microclots and vascular damage

One of the most discussed findings in long COVID research is the reported presence of microclots — tiny fibrinogen amyloid microclots — in the blood of some long COVID patients. Researchers have proposed that these microclots may partially block capillary blood flow, reducing oxygen delivery to tissues. The hypothesized result is chronic tissue hypoxia — oxygen deprivation at the cellular level — that could persist independently of viral presence. This mechanism remains an active area of investigation and debate among researchers.

Neuroinflammation

COVID-19 triggers an inflammatory response that in some patients persists long after the infection resolves. In the brain, this chronic neuroinflammation impairs neural function, disrupts neurotransmitter systems, and produces the cognitive symptoms characteristic of brain fog. Brain imaging studies in long COVID patients have documented reduced cerebral blood flow and metabolic activity consistent with neuroinflammatory damage.

Mitochondrial dysfunction

Multiple studies have documented mitochondrial dysfunction in long COVID patients — impairment of the cellular organelles responsible for energy production. This dysfunction explains the characteristic post-exertional malaise: cells cannot generate ATP efficiently, producing profound fatigue that is worsened rather than relieved by activity.

Autonomic nervous system dysregulation

Dysautonomia — dysfunction of the autonomic nervous system — is present in a substantial proportion of long COVID patients. This affects heart rate regulation, blood pressure control, digestive function, and thermoregulation, producing symptoms that appear unrelated but share a common neurological root.

How HBOT Addresses Long COVID Biology

Researchers have proposed that the mechanisms through which HBOT acts may align with the biological pathways thought to sustain long COVID symptoms — which is one reason the intervention is considered scientifically plausible rather than speculative. The following are proposed mechanisms under investigation, not established treatment effects.

  • •Microclot clearance and vascular repair (proposed) — researchers have hypothesized that high-pressure oxygen may promote fibrinolysis and help break down the amyloid microclots implicated in long COVID, and may stimulate angiogenesis — new blood vessel growth — with the aim of restoring microvascular circulation
  • •Neuroinflammation reduction (studied) — studies suggest HBOT may modulate inflammatory signaling pathways associated with chronic neuroinflammation, potentially reducing the inflammatory burden on brain tissue
  • •Mitochondrial support (proposed) — oxygen at hyperbaric concentrations may provide the substrate mitochondria need to resume normal ATP production, a possible mechanism behind reported improvements in post-exertional fatigue
  • •Neuroplasticity promotion (studied) — HBOT has been studied for its potential to support the formation of new neural connections in regions of the brain with compromised function
  • •Autonomic nervous system regulation (emerging evidence) — some clinical studies report that HBOT may help normalize autonomic function in some patients, improving heart rate variability and reducing dysautonomia symptoms

What the Clinical Research Shows in 2026

The evidence base for HBOT in long COVID has developed rapidly since 2022. The landmark study — and the research that has followed — has generated a notable clinical signal, though it remains an investigational use rather than an established, FDA-cleared treatment. This section summarizes what the research has reported.

Landmark RCT — Efrati et al., Nature Communications, 2022

This randomized, double-blind, sham-controlled trial — the gold standard of clinical research design — enrolled 73 long COVID patients with documented cognitive and symptomatic impairment. Participants received either 40 HBOT sessions or sham treatment over two months. The HBOT group showed significant improvements in global cognitive function, attention, executive function, and information processing speed — all objectively measured. Brain imaging confirmed increased perfusion in affected regions. Quality of life scores improved significantly. The sham group showed no equivalent improvement. The trial was published in Nature Communications — one of the most rigorously reviewed journals in clinical research.

Follow-on Research — Fatigue and Autonomic Function, 2023–2025

Multiple subsequent studies have expanded the evidence base established by the Efrati trial. Research published through 2025 has documented significant improvements in fatigue scores, heart rate variability measures, and quality of life in long COVID patients receiving HBOT protocols. A 2024 retrospective study of 91 long COVID patients treated with HBOT reported improvements in cognitive function, energy levels, and sleep quality in the majority of participants — with effects sustained at 3-month follow-up.

Neuroimaging Evidence — Cerebral Blood Flow Restoration

Brain imaging studies using SPECT and functional MRI have reported measurable increases in cerebral blood flow and metabolic activity in long COVID patients following HBOT treatment. Researchers have interpreted these findings as correlating with the cognitive improvements some patients report, and as pointing to a possible biological mechanism. These results are encouraging but remain an area of ongoing investigation and do not by themselves establish HBOT as a proven treatment for long COVID.

Important context — FDA clearance status

HBOT is not currently FDA-cleared specifically for long COVID or Post-Acute Sequelae of SARS-CoV-2 infection. The research cited here represents peer-reviewed clinical evidence from published studies. Patients interested in HBOT for long COVID should discuss it with their physician, who can evaluate whether off-label HBOT is appropriate for their specific situation. RxAir360 does not make claims of treating long COVID beyond FDA-cleared indications.

Is HBOT FDA-Cleared for Long COVID? What Patients Need to Know

This is the most important practical question for patients and physicians evaluating HBOT for long COVID — and the answer requires careful framing.

HBOT is not currently FDA-cleared specifically for long COVID. This means it is being used for this indication on an off-label basis — which is legal and common in medicine. Off-label use of FDA-cleared drugs and devices is standard medical practice when clinical evidence supports it. Approximately 20 percent of all prescriptions written in the United States involve off-label use of approved medications.

What matters clinically is the quality of the evidence and the professional judgment of a qualified physician. The Efrati et al. 2022 Nature Communications trial — a randomized, double-blind, sham-controlled study — is among the strongest evidence produced for any long COVID intervention. Physicians reviewing that evidence alongside their patient's specific situation can make an informed judgment about whether off-label HBOT is appropriate.

Insurance coverage for off-label HBOT use is typically not available through Medicare or standard private insurers. Patients accessing HBOT for long COVID should expect to pay out of pocket and should discuss costs with the treating facility in advance.

How to Access HBOT for Long COVID

Step 1 — Talk to your physician

Bring printed copies of the key research — particularly the Efrati et al. 2022 Nature Communications paper — to your appointment. Ask your physician to review the evidence and evaluate whether off-label HBOT is appropriate for your specific symptom profile and medical history.

Step 2 — Find a qualified hyperbaric provider

HBOT must be administered in a properly equipped clinical facility under physician supervision. Look for providers affiliated with the Undersea and Hyperbaric Medical Society (UHMS) or operating through hospital-based hyperbaric programs. Avoid providers offering soft-sided or low-pressure chambers — these do not achieve the therapeutic pressure levels used in clinical research.

Step 3 — Understand the protocol

The Efrati et al. trial used 40 sessions of HBOT at 2 ATA delivered over two months. Most clinical protocols for long COVID are based on similar parameters. Individual protocols may vary — your physician and hyperbaric provider will define the appropriate course for your situation.

Step 4 — Set realistic expectations

Clinical research shows statistically significant improvements in cognitive function, fatigue, and quality of life — but individual responses vary. Not every patient responds equivalently. Patients with more severe baseline impairment may require longer courses. Improvement may be gradual rather than immediate. Discuss realistic outcomes with your physician before beginning treatment.

Frequently Asked Questions

Is HBOT covered by insurance for long COVID?
How many HBOT sessions are needed for long COVID?
How quickly does HBOT work for long COVID symptoms?
Can HBOT help long COVID brain fog specifically?
Where can I find a physician who offers HBOT for long COVID?

Understanding Hyperbaric Oxygen Therapy — Series

Previous: Investing in HBOT Post 9 of 10 Next: RxAir360 Manufacturing

Talk to your doctor about HBOT for long COVID recovery

RxAir360 has built a patented physician-office vertical monoplace hyperbaric chamber — designed to bring clinical-grade HBOT closer to the patients who need it most. FDA 510(k) submission is next; the device is not yet cleared for sale or clinical use. Explore the evidence, talk to your physician, and contact RxAir360 for information on access as our physician network grows.

Explore HBOT Benefits For Physicians
HBOT Benefits · For Physicians · Contact

RxAir360 in the News

The RxAir360 mission to expand access to hyperbaric oxygen therapy has recently been featured in national publications. Read more about the story behind the company and its patented vertical monoplace chamber:

IBTimes International Business Times — "How Diallo M. Watts Turned a Family Health Crisis Into a Mission to Expand Access to Hyperbaric Oxygen Therapy" Wellness Voice Wellness Voice — "How Diallo M. Watts Turned a Family Health Crisis Into a Mission to Expand Access to Hyperbaric Oxygen Therapy"

About RxAir360

RxAir360 Inc. is a Bellaire, Texas (Houston area) medical device company developing a patented vertical monoplace hyperbaric oxygen therapy chamber designed for physician offices. Manufactured by Electroimpact — precision engineering partners for Boeing and Airbus — the RxAir360 chamber has been built and tested but has not yet received FDA 510(k) clearance; submission is next. The company's CARE nonprofit arm supports expanded HBOT access for uninsured and underinsured children across Texas and beyond.

rxair360inc.com 5555 W Loop South, Suite 150, Bellaire TX 77401 (240) 640-4560