“True learning is that which is conducive to the well-being of the world, not to pride and self-conceit, or to tyranny, violence and pillage.” ~Baha’u’llah

As a global scientific community, currently, we are deeply focused on finding answers within the pharmaceutical industry, our ventilators, and vaccinations to resolve the current COVID-19 pandemic. SARS-CoV-2, a betacoronavirus causing COVID-19, is no normal acting virus. It acts almost as though it has no boundaries. It is aggressive, unruly, and perhaps here to force us out of our comfort zone as a medical community to go beyond our conventional treatment options. Surely, a virus that acts out of the box requires us also to look out of the box for answers for treatment.

INTRODUCTION

SARS-CoV-2 creates an inflammatory response in the respiratory tract before it quickly turns into a ‘cytokine storm’, filling up the lungs with pus and severe inflammation that no longer allow for proper oxygen/carbon dioxide exchange. Those with predisposed chronic conditions and immune-suppression who may not be able to handle the ‘cytokine storm’ and the oxygen deprivation, are often placed on ventilators and may not survive. Those who do survive continue to experience fatigue and weakness for months. Our conventional therapies so far have focused on pharmaceuticals to disable the virus, its attachment or its promotion unto the human cell. Research on multiple pharmaceutical medications such as hydroxychloroquine (an anti-malarial drug) alone or in combination with azithromycin (an antibiotic), remdesivir (anti-viral) and ivermectin (antiparasitic) have been initiated (1, 2, 3, 4, 5 ). Amongst the clinical pharmaceutical studies, hydroxychloroquine with azithromycin combination appears to be the most effective so far in reducing the COVID-19 viral load. Despite the use of these medications, those suffering with severe symptoms continue to progress to respiratory failure. Therefore, we are still missing something. While disengaging and disarming the betacoronavirus plays an important role in reducing the initiation, promotion, and spread of COVID-19, focusing research entirely on pharmaceutical medications discounts the significant need to treat the condition of the patient, the human and cellular physiology, and the promotion of healing. As we take a step back, we realize that treating the patient is of vital importance than treating solely the virus.

PROPOSAL

I propose that we come together as one medical community, combining the best of conventional medicine with that of functional naturopathic medicine, not only to address the virus but also to evaluate, optimize, and treat the patient from a systemic perspective. Treating the whole system means addressing not only the physical and physiological disturbances but also the afflictions this virus creates in our emotional, social and mental wellbeing. When we begin with evaluating and optimizing the cellular and mitochondria function, we begin to engage the body’s own army and healing capacity against this virus. As we look at the potential options for the treatment of the cellular dysfunction resulting from COVID-19, it would be wise to evaluate one of the most naturally occurring substances in the universe, oxygen and ozone as therapy. This article focuses on the use of oxygen and ozone therapy as an effective sole or adjunctive treatment to anti-microbial therapy in COVID-19.

OXYGEN UTILIZATION IS KEY

Let’s look at one of the primary cellular interactions between the virus and our cells; however, first, let’s discuss oxygen. The exquisite interplay of oxygen (O2) and Reactive Oxygen Species (ROS) within our cells plays a vital role in the health and ability of our cells to fight infections and inflammation. Oxygen is a key player in the energy production of our cells. Oxygen is vital to every cell. Without oxygen, our cells die. We die. Too much oxygen, however, can create excessive ROS which damage our cells as well. ROS is similar to the ash that is left behind after a fire. That ash can be toxic and harmful to our cells but we also need the fire to keep warm, to keep our metabolism working, to kill infections, and so forth. For optimum cellular health, it’s a fine balance between getting sufficient oxygen but not too much so as not to produce excessive amounts of ROS (7).

Furthermore, we must understand that vitality and health of our cells do not depend on the presence of oxygen alone but, more importantly, on its utilization. It’s like having food in the kitchen, but we are not eating it. After weeks of not using the food in the kitchen, we become malnourished and weakened. It is the same with oxygen. Oxygen may be available to our cells but if our cellular engine does not have the capacity to use it, our cells gradually become oxygen deprived. Cellular decay and aging set in. The efficiency and capacity of our cells, therefore, to use oxygen becomes even more important than the presence of oxygen itself. Cellular utilization of oxygen plays a significant role in cellular repair and aging.

OXYGEN AS AN ANTIMICROBIAL

Oxygen is a strong anti-microbial. Oxygen has the capacity to break down bacterial DNA, degrade viral RNA, inactivate protein synthesis, and prevent membrane transport proteins (6). Oxygen promotes the increased activity of antibiotic medications. It enables and modulates the function of leukocytes and other white blood cells to kill infections. Thus, oxygen acts both as an antimicrobial agent and a potentiator of prescription antibiotics.

MITOCHONDRIA HEALTH AND DISEASE

During disease and aging, our cellular utilization of oxygen decreases, leading to a progression of disease and dysfunction. The oxygen utilization occurs in the mitochondria (our cell engine). The healthier the mitochondria, the better our oxygen utilization, and the slower disease forms as aging slows down. When the mitochondria ages due to excessive ROS, mutations, and damage from infections, medications, radiation, etc, its oxygen utilization declines; diseases and infections take over (8). Over time, the mitochondria decays and dies. The faster the mitochondria die, the faster we deteriorate. Mitochondria death increases the risk of multi-organ failure due to infections (10). Coronaviruses, such as SARS, attack the mitochondrial function, reducing its oxygen utilization capacity, and disabling the cell while enabling the virus to flourish (9). All this leading to multi-organ failure. Recent research shows that mitochondrial destruction and mutation occurs in COVID-19 (11). In advanced COVID-19 conditions, the damage to the mitochondria becomes greater than its oxygen utilization capacity and energy production, creating an environment that disables mitochondrial repair and oxygen utilization. Further studies to analyze the actual damage to the mitochondria by SARS-CoV-2 should be performed.

SYMPTOMS OF MITOCHONDRIAL DAMAGE

Some of the symptoms of mitochondria damage as a result of lack of oxygen utilization include: shortness of breath, exhaustion and fatigue, weakness, temperature changes (cold or fever), and generalized pain. Do these symptoms sound familiar? These symptoms are symptoms of COVID-19 but also of mitochondrial oxygen utilization dysfunction. Clinically, these symptoms confirm the presence of mitochondrial defects resulting from SARS-CoV-2 virus resulting in mitochondrial oxygenation and utilization dysfunction.

MITOCHONDRIA DAMAGE IN COVID-19

Mitochondrial damage and decay occurs with infections, especially the more aggressive ones like SARS-CoV-2. The mitochondria defect imposed by SARS-CoV-2 is now officially recognized (11). We also know that mitochondrial damage occurs with the up-regulation of ACE2 receptors, which is the binding site for the spike protein S of SARS-CoV-2 (12). So the more ACE2 receptors, the more mitochondrial dysfunction, the less oxygen is utilized by our cells, and the more aggressive the COVID-19 symptoms. One of the reasons that chronic diseases, including insulin resistance, diabetes, cancer, heart disease and immune-suppressed patients are at higher risk for complications of COVID-19, is because these patients already have a basic mitochondrial dysfunction from their disease and medications. SARS-CoV-2 attacks these already compromised mitochondrial function patients, worsening the disability in oxygen utilization while promoting further mitochondrial death, which often lead to a multi-organ failure if not corrected quickly.

VENTILATORS ARE NOT THE ANSWER

Forced oxygen through ventilators to COVID-19 patients who do not have the mitochondria capacity to utilize oxygen, increases ROS production, further damaging the mitochondria. Most of these patients already have impaired mitochondria and excessive free radicals and ROS production along with decreased oxygen utilization capacity as a result of the infection itself. When we force oxygen into the already compromised lung tissue, we create a state of hyperoxygenation (too much oxygen). Hyperoxygenation creates oxygen toxicity, stimulating more free radicals and ROS productions which exacerbates the oxidative stress, destroying more mitochondria faster.

THE ROLE OF ANTI-OXIDANTS

Anti-oxidants reduce excessive oxidative stress by cleaning up the excess free radicals, neutralizing the oxygen/ROS balance. Hence, anti-oxidants like vitamin C and A, green tea extract (EGCG), zinc, quercetin, and hesperidin have been found to be effective in reducing COVID-19 symptoms (13, 14, 15, 16, 17, 39). The use of intravenous vitamin C in the treatment of COVID-19 is becoming more and more common in various parts of the world. These anti-oxidants play an important adjunctive role in the reduction of cellular damage and ROS as well as in reducing symptoms COVID-19.

CORRECTING MITOCHONDRIAL DYSFUNCTION

The answer to correcting mitochondria dysfunction and improving oxygen utilization while improving COVID-19 symptoms, perhaps lies in the exploration and integration of out-of-the-box treatments such as intravenous ozone therapy, known as one of the oxidative therapies. Other oxidative therapies include high dose intravenous vitamin C, ultraviolet blood irradiation, and intravenous hydrogen peroxide. Ozone is an unstable molecule of three oxygen atoms, found in nature. Ozone therapy, first discovered in Europe in the late 1800’s has been used medically for over 100 years. Medical ozone consists of 95% oxygen and 5% ozone. A well-known disinfectant, ozone disrupts the activity of many hard to treat infections such as influenza, hepatitis, HIV, ebola, and more (18, 19, 20, 21, 22).

OZONE THERAPY

Medical ozone therapy is a powerful method of oxygenating the mitochondria and the cells without further damaging them (26). It corrects mitochondria oxygen utilization by repairing the mitochondria through correcting the NAD/NADH ratio, for example. Ozone therapy has been shown to improve cellular energy production and reduce oxidative stress by acting as a free radical scavenger(23). It reduces oxidative stress by acting as an antioxidant to modulate the immune response and improve blood viscosity and oxygen delivery to cells (30). Ozone activates the production of multiple endogenous antioxidants such as superoxide dismutase (SOD), glutathione peroxidase, glutathione S-transferase (GST), heat shock proteins, and phase II enzymes of drug metabolism (32). Furthermore, ozone therapy modulates inflammation through improving anti-inflammatory cytokine production (30). Ozone has direct antimicrobial effects against bacteria, fungi, parasites, and viruses (27, 28, 32). Finally, because medical ozone therapy repairs mitochondria and increases cellular oxygenation and oxygen utilization by the cell, ozone therapy may be regarded as an effective anti-aging therapy. Clinically, studies have shown benefits in the treatment of neurodegenerative conditions, diabetes, heart disease, cancer, and infections because it repairs the mitochondria while oxygenating cells and reducing the oxidative stress (29, 30, 31, 33, 34, 35)

HOW IS OZONE ADMINISTERED?

Several forms of ozone administration exist but the one most studied as an antimicrobial and mitochondrial regenerator for diseases is blood ozone therapy, known as major autohemotherapy (MAH). Ozone gas is mixed with 60-240 ml of blood drawn. After a few minutes of the combined mixture, visually one witnesses the oxygenation of the venous blood as it turns bright red. It then is irradiated with ultraviolet light prior to returning to the patient. The blood returning to the patient is now oxygenated, disinfected and rejuvenated. As discussed earlier, blood ozone therapy (BOT) can regenerate tissue and the mitochondria, act as an anti-microbial therapy and exert anti-inflammatory and analgesic (pain-relieving) influences depending on the dose of the ozone. Ozone inhalation is never performed because inhaled ozone is toxic to the lungs, disrupting the cell membrane of the lungs. Otherwise, other forms of ozone administration such as autohemotherapy, rectal insufflation, nasal and ear insufflation, topical and oral ozone are safe, inexpensive and effective in treating mitochondrial conditions and chronic and acute infections (25, 36, 37).

OZONE IN COVID-19

Gradually case reports and research from various parts of the world are beginning to document the benefits of ozone therapy in COVID-19 specifically (24, 25). The awareness of the benefits of ozone therapy in the COVID-19 pandemic is starting to be raised (38). I hope that this article brings into further awareness the incredible potentialities of medical ozone therapy for COVID-19 pandemic. Of course, this treatment needs further testing specifically for COVID-19 but so far the science has shown its potent benefits in treating infections, reducing inflammation, modulating the immune response, reducing oxidative stress, correcting mitochondria dysfunction, improving cellular oxygenation and mitochondrial oxygen utilization and reducing pain. These are all physiological processes that are dramatically disturbed in COVID-19 patients and need to be corrected quickly. Perhaps, combining ozone therapy with hydroxychloroquine and azithromycin to further potentiate their effects may be warranted.

CONCLUSION

If we are to understand SARS-CoV-2 to be a mitochondria disrupter causing a decrease in oxygen utilization by the cells, increasing inflammation and creating a cytokine storm and excessive oxidative stress, then it makes sense that we look into ozone therapy, specifically Major Autohemotherapy, as a potential treatment option or at least an adjunctive treatment option for COVID-19 crisis. Ozone therapy is safe, inexpensive and most likely will be effective in COVID-19. As a potent biological modulator, ozone therapy is worth further clinical and scientific investigation and application.

REFERENCES
  1. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-hydroxychloroquine-potential-therapy-covid-19-begins
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102549/
  3. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins
  4. https://pharmascope.org/ijrps/article/view/1973
  5. https://www.sciencedirect.com/science/article/pii/S0166354220302011
  6. https://academic.oup.com/cid/article-abstract/14/3/720/282105
  7. https://www.sciencedirect.com/science/article/pii/S0065242310500076
  8. https://www.hindawi.com/journals/bmri/2014/238463/
  9. https://www.jimmunol.org/content/193/6/3080.short
  10. https://www.tandfonline.com/doi/full/10.4161/viru.26907
  11. (https://www.mdpi.com/2077-0383/9/4/982
  12. https://www.preprints.org/manuscript/202002.0299/v1
  13. https://osf.io/p7ex8/?fbclid=IwAR2b67345SBs9r2QfJ23xH_0GEM771Qwww6EPpOSTSpQ7_x2BUu7-5CZEHo
  14. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-02851-4
  15. https://chemrxiv.org/articles/Repurposing_Therapeutics_for_the_Wuhan_Coronavirus_nCov-2019_Supercomputer-Based_Docking_to_the_Viral_S_Protein_and_Human_ACE2_Interface/11871402
  16. https://www.researchgate.net/profile/Rizki_Awaluddin3/publication/339907086_Potential_Inhibitor_of_COVID-19_Main_Protease_Mpro_From_Several_Medicinal_Plant_Compounds_by_Molecular_Docking_Study/links/5e6f89c7299bf12e23ca69c2/Potential-Inhibitor-of-COVID-19-Main-Protease-Mpro-From-Several-Medicinal-Plant-Compounds-by-Molecular-Docking-Study.pdf
  17. https://www.preprints.org/manuscript/202003.0333/v1
  18. https://www.researchgate.net/publication/333875271_The_immune_response_behavior_in_HIV-AIDS_patients_treated_with_Ozone_therapy_for_two_years
  19. https://www.tandfonline.com/doi/abs/10.1080/01919512.2012.720161
  20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070838/
  21. https://www.ncbi.nlm.nih.gov/pubmed/31898609
  22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC331270/
  23. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312702/)
  24. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3561379
  25. https://www.researchgate.net/profile/Stanislaw_Stawicki/publication/340104887_Could_tracheo-bronchial_ultraviolet_C_irradiation_be_a_valuable_adjunct_to_the_management_of_severe_COVID-19_pulmonary_infections/links/5e8519e292851c2f527432c6/Could-tracheo-bronchial-ultraviolet-C-irradiation-be-a-valuable-adjunct-to-the-management-of-severe-COVID-19-pulmonary-infections.pdf
  26. https://clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-6-113.php?jid=jide
  27. https://www.ncbi.nlm.nih.gov/pubmed/9394395
  28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC241881/
  29. https://www.ncbi.nlm.nih.gov/pubmed/7742706
  30. https://www.sciencedirect.com/science/article/abs/pii/S001429991200581X?via%3Dihub
  31. https://www.researchgate.net/publication/7896723_Adjuvant_Ozonetherapy_in_Advanced_Head_and_Neck_Tumors_A_Comparative_Study/fulltext/0f3172073829de22160880dd/Adjuvant-Ozonetherapy-in-Advanced-Head-and-Neck-Tumors-A-Comparative-Study.pdf
  32. http://www.medgasres.com/article.asp?issn=2045-9912;year=2017;volume=7;issue=3;spage=212;epage=219;aulast=Smith
  33. http://downloads.hindawi.com/journals/ecam/2004/437019.pdf
  34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260055/
  35. http://www.mmj.eg.net/article.asp?issn=1110-2098;year=2014;volume=27;issue=1;spage=85;epage=92;aulast=Saleh
  36. http://www.xn--revistaespaoladeozonoterapia-7xc.es/index.php/reo/article/view/27
  37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118245/
  38. https://www.pagepressjournals.org/index.php/ozone/article/view/9014
  39. https://www.preprints.org/manuscript/202004.0124/v1

1 Comment

  • George Denniston MD, MPH

    Hello Dr Darvish,
    I am a former guest lecturer at Bastyr.
    Is there a study at this time of Ozone therapy? Any data? Thank you.

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