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Hyperbaric oxygenation as a potential instrument for resuscitation and therapy of COVID-19 patients with cardio-respiratory dysfunction

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The novel coronavirus disease 2019 (COVID-19) has grown to become a global public health emergency. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the severe cases. There are emerging several promising directions for therapy development.

Thus, good initial results were shown by the use of stem cells, in particular the intravenous transplantation of mesenchymal stem cells (MSCs) into severe COVID-19 patients [1]. The main cause of life-threatening conditions, disability and death in COVID-19 patients may derive from an excessive inflammatory response to the virus, leading to the major complications of cytokine storm in the lung, disrupting the balance of cytokines, followed by edema, dysfunction of the air exchange, acute respiratory distress syndrome (ARDS), acute cardiac injury and secondary infections, which may lead to death.  Treatments, like MSCs could inhibit the over-activation of the immune system and promote endogenous repair by improving the microenvironment, thus they could represent a safe and effective treatment for patients with COVID-19 pneumonia, especially for the patients in critically severe conditions.

Yet, there may be additional or complementary methods to potentially fight excessive inflammation and the resulting cardio-respiratory problems, such as ARDS.

One of the potential therapeutic approaches is Hyperbaric Oxygenation Therapy (HBOT). HBOT or high pressure oxygen delivery has been gaining an increasing recognition as a versatile therapeutic approach, including diverse severe and critical conditions [2].

The HBOT general protective effect on the organism may be due to its improving energy metabolism. In many ICU cases, with a multiple range of severe indications, HBO treatment improved the survival and prevented multiple-organ failure, including preventing damage of the lungs. HBOT demonstrated protective, even life-saving effects against the most severe cardio-respiratory complications, including Acute Respiratory Distress Syndrome (ARDS), leading to a normalization of the gas exchange in the lungs and pumping function of the heart, thus preventing lethality in the patients [2].

The cardio-respiratory complications are the main cause of suffering and death also in severe COVID-19 patients. Hence the application of HBOT may be suggested as an investigational treatment for these patients.

In COVID-19, the life-threatening complications are mostly due to an excessive inflammatory response. The HBTO mechanism of action may become beneficial for such patients, since HBOT has been commonly reported to produce anti-inflammatory effects, which have been implicated as one of its major therapeutic mechanisms, for both age-related chronic and acute conditions. The protective physiological function of HBOT may further involve improvement of myocardial contraction, endogenous production of lung surfactants and corticosteroids, and anti-microbial effects.

In certain acute cases, regular ventilation may be insufficient to supply enough oxygen for the vital function of severely ill patients. The inclusion of high pressure oxygen delivery by HBOT may facilitate a more rapid recovery of vital functions and save the patients. So far hyperbaric oxygenation remains one of the most effective clinical means of oxygen delivery to deep vital tissues, hence promising for the treatment of severe consequences of the cardio-respiratory impairment generally, and in severe or critical COVID-19 patients in particular.

To the best of our knowledge, an application of HBOT against COVID-19 has not yet been practically attempted. We suggest investigating this possibility, utilizing the best existing HBOT expertise, to maximize potential benefits while preventing adverse side effects.

It must be noted that the question about the efficacy of using HBOT against acute severe impairments of vital thoracic organs (such as ARDS and others) is still debated [2]. Apparently, a necessary condition to achieve effective therapy should be proper HBO dosing, which necessitates acquiring data on dose effects in each pathological state, with close multi-parametric real-time monitoring, while maintaining strict safety conditions, to minimize infection and prevent over-stimulation and oxygen toxicity. Therapeutic regimens need to be adjusted to age-specific responses in the elderly and multi-morbid patients as compared to the younger patients, whose therapeutic regimens and benefits may be different. Further regimen distinctions should be made for HBOT under acute conditions (emergency HBOT) vs. chronic conditions (maintenance HBOT) vs. preclinical conditions (preventive HBOT). The regimens, dosages, toxicities and risk factors under the different conditions will require investigation during the trial application.

Yet, we believe, that following the differential proof of concept investigation, hyperbaric oxygen therapy may become a life-saving resuscitation measure for COVID-19 patients, who have urgent oxygen requirements and high inflammatory response.

 

Gennady Rogatsky, MD, PhD. Faculty of Life Sciences. Bar Ilan University, Israel (emeritus).

Ilia Stambler, PhD. Shmuel Harofe Geriatric Medical Center, Israel

 

Selected sources 

[1] Zikuan Leng, Rongjia Zhu, Wei Hou, Yingmei Feng, Yanlei Yang, Qin Han, et al. (2020). Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging and Disease, 11(2):216-228 http://www.aginganddisease.org/article/0000/2152-5250/ad-0-0-216.shtml

[2] Gennady G. Rogatsky and Ilia Stambler (2017). Hyperbaric oxygenation for resuscitation and therapy of elderly patients with cerebral and cardio-respiratory dysfunction. Frontiers in Bioscience, 9:230-243. https://www.bioscience.org/2017/v9s/af/484/fulltext.htm

Downlad the open letter as PDF

Hyperbaric Oxygen Therapy against COVID-19

See also

Rogatsky and Stambler – HBOT in Elderly – Frontiers in Bioscience 9, 230-243, 2017

In Russian

HBOT – Russian – 2017

Update 16 October 2020

The (initial encouraging) results of using Hyperbaric Oxygen Therapy against COVID-19 have been published. The HBO treatments were done in Moscow N.V. Sklifosovsky Research Institute for Emergency Medicine. The article entitled “The Safety of Hyperbaric Oxygen Therapy in the Treatment of Covid-19” was published in the Russian Sklifosovsky Journal of Emergency Medical Care (the article is in Russian, with an abstract in English).

https://cyberleninka.ru/article/n/bezopasnost-primeneniya-giperbaricheskoy-oksigenatsii-pri-lechenii-covid-19

According to the abstract: “We examined 32 patients with the diagnosis “Coronavirus infection caused by the virus SARS-CoV-2” (10 — moderately severe patients (CT 1–2), 22 — patients in serious condition (CT 3–4), who received course of hyperbaric oxygenation (HBO). … the patients showed an increase in blood oxygen saturation in patients in both surveyed groups, as well as positive dynamics in the form of a decrease in shortness of breath, an improvement in general well-being.”

According to the article “No patients in both groups under HBO treatment required transfer to artificial ventilation.”

https://www.rbc.ru/society/05/06/2020/5ed9d9519a7947f8f0c45ff4

https://www.youtube.com/watch?v=e0H6zPzfXNs&t=2112s

Update 11 August 2022. Another work by the same institute

HYPERBARIC OXYGENATION IN THE COMPLEX FOR LONG-COVID-INFECTION REHABILITATION MEASURES – THERAPIA 5 2022 RUSSIAN

And an Israeli work (July 2022)

https://www.gov.il/en/departments/news/tau-researchers-develop-treatment-for-long-term-covid-19-symptoms-20-jul-2022

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

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