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Hyperbaric Oxygen Therapy and Long Covid: Findings from a New Randomized Controlled Clinical Trial  

Oct 18th 2022 | By Craig P. Tanio, MD, FACP, IFMCP

Long Covid and HBOT Therapy

The number of patients with Long Covid continues to increase. One of the best news this summer came with the advent of a randomized controlled clinical trial showing significant improvement in Long Covid symptoms in patients who received hyperbaric oxygen therapy.   

Why would Hyperbaric Oxygen Therapy work with Long Covid?  

The reasons why there is long covid is not yet determined. We like to think of this as an “infectious-associated” condition as Steven Phillips suggests as it is not clear whether active infection still plays a role or not (the term post-Covid implies that the infection is done).  Potential mechanisms of Long Covid include direct brain invasion of the virus, micro-clots and thrombotic disease, mitochondrial dysfunction and vascular/endothelial injury with secondary tissue hypoxia. All mechanisms that we see in other post-viral syndromes and myalgic encephalomyelitis / chronic fatigue syndrome. 

Hyperbarics have a number of potentially beneficial effects on this condition as a result of 2 different effects of high oxygen and high pressure. Improvements that could have an ameliorative effect on long covid include:  

  • Improvement in tissue oxygenation  
  • Changes in gene expression in both oxygen-sensitive and pressure-sensitive genes  
  • Anti-inflammatory effects  
  • Increase perfusion to tissue via angiogenesis  
  • Induction of proliferation and migration of stem cells  
  • Restoration of mitochondrial function  
  • The combined effects of many of the above mechanisms can help the brain with neuroplasticity; e.g., helping the brain make new connections  

What Did the Result Show?  

Hyperbaric oxygen therapy or sham were given to 73 patients with long-Covid for 5 days weekly for 8 weeks, e.g., 40 treatments. The protocol was for 90 minutes at 2.0 atmospheres in a hard chamber with 100% oxygen and air breaks every 20 minutes. Symptom questionnaires, formal cognitive testing and MRI studies were performed pretreatment and at 1 to 3 weeks post-treatment.  The following improvements were seen:  

  • Improvement in symptoms, especially energy, emotional well-being, anxiety, depression  
  • Improvement in cognitive performance especially executive function, information processing  
  • Improvement in brain circulation as measured by perfusion magnetic resonance imaging in the L&R supramarginal gyrus, L anterior cingulate gyrus, R superior parietal lobe, L supplementary motor area, L parahippocampal gyrus and R insula.  
  • The improvement in anatomical areas correlate closely with the seen improvements in cognitive improvements  

Why is Hyperbaric Oxygen Therapy So Controversial?  

“Hyperbaric oxygen has a checkered history as a therapy for various disorders, due to studies that were small and poorly controlled…. This provocative report is well-controlled and shows objective improvements in the brain that correlate with symptom improvement. For this reason, the report surely will lead other groups to try to confirm these findings”  

Anthony Komaroff, MD  

Founding Editor, NEJM Journal Watch  

A major reason that evaluations of Hyperbaric Oxygen Therapy on neurologic function have been so controversial has been the historical inability to create the right placebo controls.  

The role of a placebo in research is to isolate the effect of the treatment itself.  

It’s easy enough to have a placebo with a drug study – just give patients a blue pill that has sugar instead of the drug.  

But how do you create fake or sham placebo treatments with hyperbaric oxygen? The solution 20 years ago was to use a soft chamber where patients got 1.3 atmospheres of pressure and room air. However, in many of these studies, both the placebo group AND the treatment group got better, because 1.3 atmospheres of pressure was not exactly a placebo. A recent Veteran Administrations review on hyperbaric oxygen in traumatic brain injury alluded to the potential therapeutic effect of the “ritual” of putting patients in a hyperbaric oxygen chamber.  

The Israeli research team behind the recent Long Covid study solved this problem by creating the illusion of pressure in the placebo group rather than actual persistent pressure. Patients were in a large multi-chamber hyperbaric oxygen chamber and for the first five minutes of a 90-minute treatment, the pressure was at 1.2 atmospheres, and they had the feeling that the pressure was being increased in the room. After the first five minutes, the pressure was turned down to 1.03 atmospheres where it remained for most of their treatment.  Patients in the control group received room air in a mask rather than 100% oxygen. The authors showed that many of the treatment patients thought they were in the control group and vice versa and this misperception was balanced on both sides. This is significant progress in the study of hyperbarics. Following this research design should allow future research studies to put the placebo question to rest.  

As a result, this study and others coming out of the Efrati group in Israel meet the gold standard of a blinded placebo control randomized trial. We can hope that over time, these improvements in methodologies will result in insurance coverage for HBOT for a variety of neurologic indications that heretofore have been blocked by these methodologic issues. 

Hyperbaric Treatment at Rezilir Health 

At Rezilir, we currently offer hyperbaric oxygen therapy treatments in two high-pressure Fortius 420 chambers that are capable of being pressurized from 1.3 ATA to 2.0 ATA.  Your session in the chamber will run anywhere from 30 to 90-minutes, depending on the treatment plan created specifically for you. Pressurization up to the appropriate atmospheric pressure will take 15-20 minutes, or possibly longer (depending on your ability to adjust for the increased pressure). Depressurization will be about the same depending on your ability to adapt. The temperature in the chamber may rise by 10 degrees so you may feel warm, but in contrast, you may also feel cold, especially during depressurization. Please dress appropriately. You will not need to change into special static-free clothing for this treatment as we do not pressurize the chamber with 100% oxygen. 

You will be assessed by the nurse practitioner or another clinician to make sure it is safe for you to enter the chamber.  If you have had a recent upper respiratory or ear infection, you may find it uncomfortable to reach the appropriate pressure, which could prevent you from completing treatment. If you have had recent surgery to your eardrum, trauma to your chest (such as a car accident or surgery), collapsed lung, a clot to your lung or anywhere else in your body, you will not be allowed into the chamber. If you are actively being treated for cancer, have clips in your brain, brain tumor or any brain abnormality, you will be required to have a letter of approval and an order for treatment from your Oncologist or Neurologist. During your assessment, it will be determined whether you will be allowed in the chamber.  

Rezilir’s chambers are solid metal, not clear, which may bother some people. If you have severe claustrophobia, you can visit the office and see how large the chamber is and possibly even getting in to see how comfortable it is on the inside, without pressure. Each chamber has 5 windows which allows for plenty of light to shine inside. You will be allowed to bring inside with you a computer, tablet, or smart phone to help pass the time. Brain games are also a great way to spend your time inside the chamber and help to increase neurogenesis or the growth of the brain.   

Hyperbaric Oxygen Therapy Chamber

Our chambers are thoroughly cleaned and disinfected with hydrogen peroxide after each use. Your safety and health are considered a priority here at Rezilir Health. 

If you have any questions about hyperbaric oxygen therapy and would like to make an appointment, please contact us via our website or call the office at 786-780-1188.



  1. NEJM Journal Watch  
  1. Zilberman-Itskovich S et al. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: Randomized controlled trial. Sci Rep 2022 Jul 12; 12:11252. ( )  

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