New long-COVID treatment developed at Tel Aviv University

Effective high-pressure oxygen treatment is now available for millions suffering from long-term COVID-19 symptoms.

 SARS-CoV-2, the novel coronavirus behind COVID-19 (Illustrative). (photo credit: fusion medical animation/unsplash)
SARS-CoV-2, the novel coronavirus behind COVID-19 (Illustrative).
(photo credit: fusion medical animation/unsplash)

Patients with long-term COVID-19 symptoms who are exposed to hyperbaric (high-pressure oxygen) therapy (HBOT) intensive show a significant improvement in cognitive, neurological and psychiatric functions.

Following a groundbreaking new study at Tel Aviv University (TAU), the treatments were accompanied by advanced magnetic resonance imaging (MRI) imaging of the patients’ brains, identifying damage from the COVID-19 virus and linking the images with clinical findings before and after HBOT treatment.

The first of its kind in the world, the study introduced a promising treatment for long-term COVID-19 symptoms based on advanced HBOT. Long COVID, which affects as many as a third of patients who were infected by the COVID-19 virus but weeks or months after they recover is characterized by a range of debilitating cognitive symptoms such as inability to concentrate, brain fog, forgetfulness and difficulty recalling words or thoughts. These symptoms continue for more than three months and sometimes up to two years.

“Today, we understand that in some patients, the COVID-19 virus penetrates the brain through the cribriform plate, the part of the skull located just above our nose, and triggers chronic brain injury

 Prof. Shai Efrati, head of the Sagol Center and a faculty member at TAU’s Sackler School of Medicine

Until now, no effective therapy has been suggested, leaving many millions of sufferers around the world with no relief. The researchers said that the study “is the first randomized, controlled trial to demonstrate a real solution for long COVID. Patients exposed to an intensive protocol of HBOT treatments showed significant improvement compared to the control group. For millions suffering from long-term COVID-19 symptoms, the study provides new hope for recovery.”

 Shamir Medical Center (credit: SHAMIR MEDICAL CENTER) Shamir Medical Center (credit: SHAMIR MEDICAL CENTER)

The study, just published in the prestigious journal Scientific Reports under the title “Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: Randomized controlled trial,” was conducted by the Tel Aviv University and Shamir Medical Center (Assaf Harofeh). It was led by Prof. Shai Efrati, head of the Sagol Center and a faculty member at TAU’s Sackler School of Medicine and Sagol School of Neuroscience, and by Dr. Shani Itskovich Zilberman from the Sagol Center for Hyperbaric Medicine and TAU’s Sackler School of Medicine.

Other chief contributors were Dr. Merav Catalogna, lead data scientist from the Shamir Medical Center, and Dr. Amir Hadanny from the Sagol Center and TAU’s Sackler School of Medicine.

“Today, we understand that in some patients, the COVID-19 virus penetrates the brain through the cribriform plate, the part of the skull located just above our nose, and triggers chronic brain injury – mainly in brain regions in the frontal lobe and responsible for cognitive function, mental status and pain interpretation,” explained Efrati. “Consequently, affected patients experience a long-term cognitive decline, with symptoms such as brain fog, loss of concentration and mental fatigue. In addition, since the frontal lobe is damaged patients may suffer from mood disturbance, depression, and anxiety.”

THESE CLINICAL symptoms, identified in patients all over the world, were corroborated by the World Health Organization (WHO) in an official definition of so-called “long COVID” issued in October 2021, including cognitive dysfunction as one of the common symptoms. A recent study from the Universities of Cambridge and Exeter reported that 78% of long COVID patients had difficulties with concentration; 69% reported brain fog; and 68% complained of forgetfulness. Thus, long-term COVID-19 effects can be very detrimental to the sufferer’s quality of life, and no effective treatment has yet been found.

In the new TAU-led study, they used HBOT, which has already been proven effective in the treatment of other forms of brain injury including stroke, trauma, age-related cognitive decline and treatment-resistant PTSD, to the global effort to find a solution for long COVID-19.

The study, designed as a prospective, randomized, double-blind and placebo-controlled clinical trial, included 73 patients with reported post-COVID-19 cognitive symptoms such as inability to concentrate, brain fog, forgetfulness and difficulty recalling words or thoughts, persisting for more than three months following an RT-PCR test confirming COVID-19 infection.

We believe that the beneficial effects of the unique treatment protocol in this study can be attributed to renewed neuroplasticity and increased brain perfusion in regions associated with cognitive and emotional roles.”

 Dr. Shani Itskovich Zilberman 

Participants were divided into two groups – 37 patients received HBOT treatment, while 36 patients served as a placebo-controlled group. Both patients and investigators were unaware of their designated treatment protocol. The unique protocol consisted of 40 daily HBOT sessions, five sessions per week within a two-month period, in which patients entered a multi-place HBOT chamber and breathed 100% oxygen by mask at two atmospheres absolute (ATA) for 90 minutes with oxygen fluctuations. The control group received placebo treatment, breathing normal air.

In addition, all participants underwent a computerized cognitive test, as well as advanced high-resolution brain imaging at two points in time – when entering the trial and after its completion.

Encouraging results

The results were very encouraging. Patients treated with HBOT showed significant improvement, while in the control group long COVID symptoms remained largely unchanged. In HBOT-treated patients, the greatest improvements were exhibited in the global cognitive function, attention, and executive functions (the capacity to plan, organize, initiate, self-monitor and control one’s responses in order to achieve a goal). Other benefits included better information processing speed, improved psychiatric symptoms, more mental energy, better sleep quality and less body pain. All clinical findings were correlated with the participants’ brain images, indicating significant change in the parts of the brain related to each function, which had been visibly damaged by the COVID-19 virus.

Itskovich Zilberman said that “we know that HBOT repairs brain damage through a process of regeneration – generating new neurons and blood vessels. We believe that the beneficial effects of the unique treatment protocol in this study can be attributed to renewed neuroplasticity and increased brain perfusion in regions associated with cognitive and emotional roles.”

“For the first time, our study proposes an effective treatment for the debilitating long COVID syndrome, repairing brain injury with an intensive protocol of HBOT,” concluded Efrati. “Moreover, the study reveals the very real biological damage to brain tissues induced by the COVID-19 virus and how repairing this damage reduces symptoms and can eventually lead to recovery. From a broader perspective, these findings can also suggest that other neurological and psychiatric syndromes might be triggered by biological agents such as viruses, opening new possibilities for future treatments.”