#hbottherapy

BY BROOKS LEITNER

Imagine lying back in an enclosed chamber where you bask for 90 minutes in a sea of pure oxygen at pressures two to three times that felt at sea level. This is the world of hyperbaric oxygen therapy (HBOT), a technology that’s been around for decades and is now being explored as a possible treatment for Long COVID.

"The silence on the inside is deafening at first,” says John M.,* who has undergone dozens of HBOT treatments for his persistent Long COVID symptoms. Fortunately, there is a television outside the chamber in view, and it is easy to communicate with the provider if needed. While the potential protocol is still being refined, patients may undergo up to 40 HBOT sessions to address some of the most problematic, lingering symptoms of this complex condition.

HBOT is a therapeutic process that has been widely used to treat such conditions as decompression sickness in scuba divers, carbon monoxide poisoning, and diabetic foot ulcers. In HBOT, the body is exposed to 100% oxygen, a significant increase from the 21% oxygen concentration we typically breathe. The therapy takes place in an enclosed chamber where the air pressure is elevated above normal levels. The combination of high-pressure and high-oxygen conditions enhances the amount of oxygen that can reach the body's tissues. The hope is that this therapy can provide the same relief and healing to people with Long COVID that it does for those with other conditions.

According to John M., HBOT was the first treatment that helped with his sleep and reduced his heart palpitations. “At one point after hospitalization, my Long COVID symptoms were so bad that I could barely walk or talk. HBOT was a great tool that really assisted with my recovery,” he said. John added that he hopes the medical community will achieve a better understanding of how HBOT can help relieve suffering for patients with Long COVID and that more research will increase access to this innovative therapy.

Does HBOT improve Long COVID symptoms? One key observation from the work of Inderjit Singh, MBChB, an assistant professor at Yale School of Medicine (YSM) specializing in pulmonary, critical care, and sleep medicine, is that Long COVID patients often experience debilitating fatigue. Based on Dr. Singh’s previous Long COVID research, the exhaustion is thought to be linked to the muscles’ inability to efficiently extract and utilize oxygen.

To picture how HBOT might work, you can think of your muscles as engines sputtering, struggling to get the fuel they need. If oxygen is the gas that fuels the muscles, it’s as if you are trying to complete your daily routine while the gas tank is running on “empty.” By aiming to directly address this oxygen utilization impairment, HBOT may be a potential solution.

A systematic review by researchers at the China Medical University Hospital noted that HBOT could tackle another major factor in the Long COVID puzzle: oxidative stress. This relates to the body's struggle to maintain balance when harmful molecules, known as free radicals, run amok, causing chronic inflammation.

Research co-authored by Sandra K. Wainwright, MD, medical director of the Center for Hyperbaric Medicine and Wound Healing at Greenwich Hospital in Connecticut, suggests that HBOT, with its high-oxygen environment, might dampen this chronic inflammation by improving mitochondrial activity and decreasing production of harmful molecules. Other potential benefits of HBOT in the treatment of Long COVID may include restoration of oxygen to oxygen-starved tissues, reduced production of inflammatory cytokines, and increased mobilization of hematopoietic stem cells—primary cells that transform into red blood cells, white blood cells, and platelets.

HBOT for Long COVID: Current and ongoing research Several small-scale reports have indicated that HBOT is safe for patients with Long COVID.

To address this question, a trial that followed the gold standard of modern medical research—a randomized, placebo-controlled, double-blind design—assigned 73 Long COVID patients to either receive 40 sessions of HBOT or a placebo of only 21% oxygen. The study observed positive changes in attention, sleep quality, pain symptoms, and energy levels among participants receiving HBOT. In a longitudinal follow-up study published in Scientific Reports, the authors at the Tel Aviv University found that clinical improvements persisted even one year after the last HBOT session was concluded. In a second study, the same authors focused on heart function, measured by an echocardiogram, and found a significant reduction in heart strain, known as global longitudinal strain, in patients who received HBOT.

In another study, 10 patients with Long COVID underwent 10 HBOT treatments over 12 consecutive days. Testing showed statistically significant improvement in fatigue and cognitive function. Meanwhile, an ongoing trial at the Karolinska Institute in Sweden has reported interim safety results wherein almost half of the Long COVID patients in the trial reported cough or chest discomfort during treatment. However, it was unclear whether HBOT exacerbated this symptom or if this adverse effect was due to the effort of participation by patients suffering from more severe Long COVID symptoms.

Is HBOT currently available as a treatment for Long COVID? For HBOT to become a mainstream treatment option for Long COVID, several critical priorities must be addressed. First, there is currently no established method for tailoring HBOT dosages to individual patients, so researchers must learn more about the specific features or symptoms that indicate potential benefits from HBOT. At the same time, we need to identify factors that may be associated with any adverse outcomes of HBOT. And finally, it’s important to determine how long these potentially beneficial effects last in a larger cohort. Will just a few HBOT trials be enough to restore patients to their baseline health, or will HBOT become a recurring component of their annual treatment regimen?

For now, HBOT remains an experimental therapy—and as such is not covered by insurance. This is a huge issue for patients because the therapy is expensive. According to Dr. Wainwright, a six-week course of therapy can run around $60,000. That’s a lot to pay for a therapy that’s still being studied. In the current completed studies, different treatment frequencies and intensities have been used, but it’s unclear how the treatment conditions affect the patient’s outcome.

“I have had some patients notice improvements after only 10 or 15 treatments, whereas some others need up to 45 treatments before they notice a difference,” notes Dr. Wainwright. “I think that HBOT is offering some promising results in many patients, but it is probably a strong adjunctive treatment to the other spectrum of things Long COVID patients should be doing, like participating in an exercise, rehab, and nutritional program.”

Dr. Singh notes that “a major challenge for research is the heterogeneity of Long COVID. It is hard to determine which symptoms to treat and enroll patients into trials based on them.”

Perhaps treatments that target multiple issues caused by Long COVID, like HBOT, may help overcome this challenge.

*Not his real name.

Brooks Leitner is an MD/PhD candidate at Yale School of Medicine.

The last word from Lisa Sanders, MD: Hyperbaric oxygen therapy (HBOT) is just one of the many existing treatments that are being looked at to treat Long COVID. We see this with many new diseases—trying to use a treatment that is effective in one set of diseases to treat another. And there is reason for optimism: We know that HBOT can deliver high levels of oxygen to tissues in need of oxygen. That’s why it’s used to treat soft tissue wounds. If reduced oxygen uptake is the cause of the devastating fatigue caused by Long COVID, as is suggested by many studies, then perhaps a better delivery system will help at least some patients.

Studies referenced:

bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08002-8

www.ncbi.nlm.nih.gov/pmc/articles/PMC8806311/

www.nature.com/articles/s41598-024-53091-3

www.nature.com/articles/s41598-022-15565-0

www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1354088/full