A groundbreaking new study from Tel Aviv University, the first of its kind in the world, found a promising treatment for long-term COVID-19 symptoms, based on advanced hyperbaric (high-pressure oxygen) therapy (HBOT).

Long COVID, which affects up to 30% of patients infected by the COVID-19 virus, is characterized by a range of debilitating cognitive symptoms such as inability to concentrate, brain fog, forgetfulness and difficulty recalling words or thoughts – persisting for more than three months, and sometimes up to two years. To date, no effective therapy has been suggested, leaving many millions of sufferers around the world with no remedy.

The researchers: “Our study is the first randomized controlled trial to demonstrate a real solution for long COVID. Patients exposed to an intensive protocol of Hyperbaric Oxygen Therapy 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.”

Long Covid – Detrimental to Quality of Life

The study was conducted by the Sagol Center for Hyperbaric Medicine and Research at Tel Aviv University and the Shamir Medical Center (Assaf Harofeh). It was led by Prof. Shai Efrati, Director 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 (Assaf Harofeh), and Dr. Amir Hadanny from the Sagol Center and TAU’s Sackler School of Medicine. The paper was published in Scientific Reports.

Prof. Efrati explains: “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, responsible for cognitive function, mental status and pain interpretation. 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.”

According to Efrati, these clinical symptoms, identified in patients all over the world, were corroborated by the World Health Organization 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-term COVID-19 patients experienced difficulties with concentration, 69% reported brain fog, and 68% reported forgetfulness. “Thus, long-term COVID-19 effects can be very detrimental to the sufferer’s quality of life,” continues Efrati, “and no effective treatment has yet been found.”

Prof. Shai Efrati

HBOT – Proven Effective Against other Brain Injuries

“In our study, we harnessed Hyperbaric Oxygen Therapy, already proven effective in the treatment of other forms of brain injury such as stroke, trauma, age-related cognitive decline and treatment-resistant PTSD, to the global effort to find a solution for long COVID-19,” explains Efrati.

The study, designed as a prospective, randomized, double-blind, 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.

Participants were divided into two groups: 37 patients received HBOT treatment, while 36 patients served as a sham-controlled group, receiving placebo treatment. 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 2 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 (profusion MRI and DTI) at two points in time – when entering the trial and after its completion.

Improved cerebral blood flow by HBOT in patient suffering from post-COVID symptoms (photo:  Sagol Center for Hyperbaric Medicine)

Repairing through Regeneration

The results were highly 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 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.

Dr. Shani-Itskovich Zilberman: “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.”

Prof. Efrati: “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. 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.” 

Note: For patients with long COVID and other neurological disorders, reliable high-quality HBOT is now available at Aviv Clinics in Florida and Dubai, international arms of the Sagol Center at Shamir Medical Center (Assaf Harofeh) in Israel – administering the same strict protocols, with additional cognitive, physical and nutrition support provided to patients.

A new study by Tel Aviv University and Ben Gurion University of the Negev, in collaboration with the Israeli Ministry of Health, found that the fourth COVID-19 vaccine is effective in protecting the elderly from the Omicron variant.

The groundbreaking study included approximately 40,000 elderly Israelis living in institutions supervised by the Ministry of Health’s “Senior Shield” program, a task force launched by Israel’s government to oversee the prevention and control of COVID-19 in the country’s geriatric facilities. According to its results, elderly at-risk individuals vaccinated with the fourth dose of the Pfizer vaccine have a 34% reduced risk of contracting the Omicron variant, a 64-67% reduced risk of requiring hospitalization due to COVID, and a 72% reduced risk of death from the virus.

The study was led by Prof. Khitam Muhsen and Prof. Dani Cohen of the School of Public Health at Tel Aviv University, Prof. Ron Dagan of Ben Gurion University, Prof. Nimrod Maimon, director of the Internal Medicine Department at Soroka Medical Center and until recently head of the Ministry of Health’s Senior Shield program, as well as program staff members Ami Mizrahi, Omri Bodenheimer, and Boris Boltyansky, in collaboration with Lea Gaon and Zafrira Hillel-Diamant of the Ministry’s Department of Geriatrics. The study was published in the prestigious journal JAMA Internal Medicine.

Particularly Vulnerable Population

“Our study compared 24,088 residents of Senior Shield facilities who received a fourth dose of the Pfizer vaccine – that is, the second booster shot – with 19,687 residents who were vaccinated with the first three doses four months or more prior to the follow-up, but who chose not to get the second booster,” explains Prof. Muhsen.

“These are residents of geriatric institutions, nursing homes and assisted living facilities that are part of the Ministry of Health’s Senior Shield system – a total of about 1,000 institutions across the country. This population is particularly vulnerable to infection, morbidity, and mortality from the coronavirus, due to the nature and living conditions of the institutions, the fact that many residents need help with daily activities, and the previous health issues that many of the residents suffer from.”

When the Omicron wave spread throughout Israel between January and March of this year, there was no registered and available vaccine for this variant, which underwent significant mutations in the spike protein that allows the virus to attach to and penetrate human cells. Because the existing COVID-19 vaccines target the spike protein, there has been much discussion in Israel and the rest of the world about the effectiveness of existing vaccines against the Omicron variant in general, and with regards to a second booster shot. Israel was the first country to approve the second booster (the fourth dose of the vaccine) for those aged 60 and above. The present study is based on data from the Senior Shield population database, which constituted the first large group to receive the second booster. Prof. Muhsen points out that this new study was conducted on a national scale, and that it successfully addressed the methodological problems that characterize observational epidemiological studies on the effectiveness of COVID vaccines.

Fourth Dose Saved Many Lives

“We monitored the infections, hospitalizations and mortality rates in these two groups throughout the Omicron wave, and found that the members of the group that received the fourth vaccine were infected at a rate that was 34% less than the control group; were hospitalized for mild-to-moderate illness 64% less, and for severe illness 67% less than the control group; and had a mortality rate that was 72% less than the group vaccinated with only the first three doses,” says Prof. Muhsen.

“These are significant data, because the Senior Shield population is one of the groups who suffer the most severe morbidity from the coronavirus, at a much higher rate than the general population. We assume that the fourth dose of the vaccine boosted the level of neutralizing antibodies, which conferred cross-protection against the Omicron variant. Our study points to the significant benefit of administering the fourth dose of the vaccine and confirms that the policy adopted by the State of Israel was the correct one. The decision to vaccinate at-risk populations with the fourth dose was a wise choice that saved a lot of human lives.”

Prof. Muhsen adds: “This is a groundbreaking and innovative study based on a database of the elderly population in care facilities. Previous studies have been conducted in the general population, and therefore also among relatively young populations with an average age of around 72, whereas the average age in our study was 80. Moreover, in general, people who go to be tested or vaccinated against COVID tend to exhibit positive health behaviors, so it is very difficult to compare their morbidity levels to those of unvaccinated people or those who have been vaccinated with three doses. We have no information as to why some of the residents chose not to receive the fourth vaccine dose, but both groups in our study underwent routine and ‘blind’ COVID tests according to uniform Senior Shield protocol, regardless of whether they received the vaccine. Therefore, our study was less affected by the ‘healthy vaccinee effect,’ and its results can also be applied to other populations, in Israel and around the world.”

According to Prof. Dani Cohen, “The study indicates that giving booster shots and raising the level of antibodies through a vaccine based on the original COVID-19 strain provides significant protection against the onset of serious illness even after infection with new variants, including those that are very different from the original, such as Omicron.”

Prof. Nimrod Maimon adds that “The task of protecting institutions for people living outside of the home is a very important aspect of the Ministry of Health’s Senior Shield program. The database that the project has built and accumulated about the institutions and their residents has allowed for rapid and effective vaccination campaigns, which have yielded dramatic results in curbing illness from the coronavirus amongst these populations. The impressive results of the program have received widespread international praise, with health authorities from many countries around the world seeking to learn from the Senior Shield program.”

Prof. Ron Dagan concludes that the results presented in the study demonstrate once again the critical role of vaccines and the use of structured and effective systems in curbing waves of severe morbidity and mortality in at-risk populations.

A new study from Tel Aviv University reveals that solar exposure increases appetite in males, but not in females. It is the first gender-dependent medical study ever conducted on UV exposure, and for the first time, the molecular connection between UV exposure and appetite was deciphered.

Skin as Regulator of Appetite

The groundbreaking study was led by Prof. Carmit Levy and PhD student Shivang Parikh of the Department of Human Molecular Genetics and Biochemistry at TAU’s Sackler Faculty of Medicine. It was conducted in collaboration with many researchers in Israel and worldwide, including contributors from Tel Aviv Sourasky (Ichilov), Assuta, Meir, and Sheba Medical Centers, along with Dr. Yiftach Gepner and Dr. Lior Bikovski from TAU’s Sackler Faculty of Medicine, and Prof. Aron Weller of Bar-Ilan University. The paper was published in the prestigious journal Nature Metabolism.

The study was based on epidemiological data collected in a year-long survey about the eating habits of approximately 3,000 Israelis of both sexes, including self-reports from students who had spent time in the sun, combined with the results of a genetic study in a lab model. The findings identify the skin as a primary regulator of energy and appetite (metabolism) in both lab models and humans.

Prof. Carmit Levy

Estrogen Hormone Blocks Urge to Eat in Women

The study unravels the differences between males and females in the activation of the metabolic mechanism. The researchers explain that in males of both animal species and humans, sun exposure activates a protein called p53, to repair any DNA damage in the skin that might have been caused by the exposure. The activation of p53 signals the body to produce a hormone called ghrelin, which stimulates the appetite.

In females, the hormone estrogen blocks the interaction between p53 and ghrelin, and consequently does not catalyze the urge to eat following exposure to the sun.

The researchers explain that there is a dramatic metabolic difference between males and females, impacting both their health and their behavior. However, so far it has not been established whether the two sexes respond differently to environmental triggers such as exposures to the sun’s UV radiation.

“We examined the differences between men and women after sun exposure and found that men eat more than women because their appetite has increased. Our study was the first gender-dependent medical study ever conducted on UV exposure, and for the first time, the molecular connection between UV exposure and appetite was deciphered. Gender-dependent medical studies are particularly complex, since twice the number of participants is required to find statistically significant differences,” explains Prof. Levy.

“As humans, we have cast off our fur and consequently, our skin, the largest organ in our body, is exposed to signals from the environment. The protein p53, found in the skin, repairs damage to the DNA caused by sun exposure, but it does more than that. It signals to our bodies that winter is over, and we are out in the sun, possibly in preparation for the mating season. Our results provide an encouraging basis for more research, on both human metabolism and potential UV-based therapies for metabolic diseases and appetite disorders,” Prof. Levy concludes.