|Year : 2020 | Volume
| Issue : 2 | Page : 1-4
“Ozone” - A better alternative in COVID-19 pandemic
Khaja Javed Khan1, Gautam Das2
1 Alleviate Pain and Spine Clinic, Bengaluru, Karnataka, India
2 Daradia: The Pain Clinic, Kolkata, West Bengal, India
|Date of Submission||16-Jul-2020|
|Date of Acceptance||27-Oct-2020|
|Date of Web Publication||08-Mar-2021|
Khaja Javed Khan
No. 10, 4th Main, K.R.Gardens, Murugeshpalya, Old Airport Road, Bengaluru - 560 017, Karnataka
Source of Support: None, Conflict of Interest: None
Ozone is a molecule consisting of three atoms of oxygen in a dynamically unstable structure. Ozone gas has been used in pain medicine practice for intraarticular injections, intradiscal, periforaminal or intraforaminal injections. Ozone is inherently bacteriostatic, fungicidal, and virucidal. The world is now facing one of the biggest crises known to humankind, the Coronavirus pandemic. This COVID-19 is multiplying at an unprecedented pace, affecting the population worldwide. Coronaviruses have abundant cysteine in their spike proteins that may be easily and safely exploited with ozone (or other oxidation) therapy. Cysteine residues are also abundant in viral membrane proteins and must be “conserved” for viral cell entry. Ozone has a unique ability to inactivate cysteine dependent proteins. Ozone injections in pain medicine have reported encouraging effects in pain control and functional recovery. All of these factors, coupled with the comparatively low cost of Ozone make it an attractive alternative option compared to platelet-rich plasma or steroid injections in the present COVID-19 pandemic crisis.
Keywords: Coronavirus, COVID-19, ozone, platelet-rich plasma, steroid
|How to cite this article:|
Khan KJ, Das G. “Ozone” - A better alternative in COVID-19 pandemic. J Recent Adv Pain 2020;6:1-4
| Introduction|| |
Ozone (O3) gas, which was discovered in the mid-nineteenth century, is a molecule consisting of three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. The gas is colorless, acrid in odor and explosive in liquid or solid form. It has a half-life of 40min at 20°C and about 140 min at 0°C. Its basic function is to protect humans from the harmful effects of ultraviolet radiation.,, Ozone has remarkable health benefits in dental caries, reduction of blood cholesterol, stimulation of antioxidative responses, modification of oxygenation in resting muscle and it is also used in the complementary treatment of hypoxic and ischemic syndromes.,,, The world is now facing one the biggest crisis known to humankind, the coronavirus pandemic. This COVID-19 is multiplying at an unprecedented pace, affecting the population worldwide.
| COVID-19|| |
In December 2019, there occurred an outbreak of a new unknown pathogen in Wuhan, China. Over the next few weeks, infection became widespread, affecting most of the countries in the world. The World Health Organization on February 11, 2020, officially named it as coronavirus disease 2019, abbreviated as COVID-19. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), also known as 2019 novel coronavirus. 1 Most of the infected patients resolve acutely and have mortality rate of 2%–3.85%.,
In COVID-19, there is an increase in inflammatory cytokines and chemokines such as interleukin (IL)-1, IL-2, IL-6, IL-7, IL-8, granulocyte colony-stimulating factor, interferon-gamma inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-alpha, tumor necrosis factor-alpha and ferritin.,
SARSCoV-2 primarily affects the respiratory system, but other organ systems can also get affected. Evidence shows that there is the human-to-human transmission of SARS-CoV-2 and is mainly transmitted through respiratory droplets generated by coughing, sneezing, or exhalation. The transmission also occurs by touching-direct touch or touch to contaminated surfaces or objects and then touching own mouth, nose, or possibly eyes.
| Ozone Therapy in Treatment of COVID-19 Patients|| |
Many therapies have been tried in the treatment of coronavirus, but to no avail. Coronaviruses have abundant cysteine in their spike proteins that may be easily and safely exploited with ozone (or other oxidation) therapy. Cysteine residues are also abundant in viral membrane proteins and must be “conserved” for viral cell entry.
Blood, when treated with ozone, immediately reacts with electron-rich double bonds of lipids and other molecules, leading to the formation of weak oxidant metabolites called ozonides. Ozonides act as messengers for the key biochemical and immune-modulating effects of the therapy. The Menendez Cuban group found that preconditioning animals with ozone is as powerful as dexamethasone in reducing tumor necrosis factor α in subsequent endotoxic shock. This could be key in solving the problem of “cytokine storm,” that occurs due to pulmonary infection in coronavirus affected individuals.,,
Coronavirus structure has its spike and envelope proteins rich in cysteine, similar to the Ebola virus. Ozone has a unique ability to inactivate cysteine dependent proteins. Furthermore, the coronavirus spike protein contains tryptophan, which is second to cysteine in vulnerability to oxidation.
| Ozone Therapy in Pain Medicine Practice|| |
Ozone when utilized as an intra-articular injection, has been seen to decrease pain along with immunomodulatory effects on cartilage and reduction of oxidative stress. Ozone, due to its highly reactive nature stimulates fibroblastic joint repair, reduces inflammation, and promotes new cartilage growth when injected inside a joint. It inhibits the pro-inflammatory and pro-oxidative environment in knee osteoarthritis, also improves tissue oxygenation through vasodilatation and stimulation of angiogenesis.
Ozone has been used for intraarticular knee injections in mild to moderate osteoarthritis. Lopes De Jesus et al. In their study found greater efficacy of O3 compared to placebo in pain relief, joint function, and quality of life. Mishra et al. found a greater success rate in the Ozone group than in those who received a corticosteroid injection over a follow-up of 6 months. Babaei-Ghazani et al., who suggest that, although steroid injection showed an earlier improvement, Ozone seemed to be more persistent and have a longer-lasting effect.
Intradiscal injection of ozone gas has been used as an alternative to epidural steroids and surgical discectomy. Ozone is a strong oxidizer and its application to the nucleus results in the cleaving of the proteoglycan molecules and neutralization of the negatively charged sulfate side chains. This likely reduces the disc's ability to retain water and results in a reduction of the herniation volume.
Gallucci et al. in their study compared intradiscal and intra-foraminal injections of ozone combined with steroids or steroids alone. At 6 months follow-up, they found a statistically better outcome in the ozone group.
Muto et al. reported on 2200 patients treated with intradiscal and foraminal ozone injections and followed them up for 18 months. Ozone injections showed maximum improvement at 6 months, and the results were stable to 18 months.
| Ozone as an Alternative in Pain Medicine Practice|| |
In the current situation, due to the Coronavirus pandemic, we as pain physicians need to be very judicious while doing the various pain interventions. It becomes all the more important that we use the right agent during the injections.
Platelet-rich plasma injections are utilized as a regenerative treatment option forosteoarthritis, tendinopathies, partial tears of ligament or tendons, etc. They have shown good success but need to be supported with conclusive evidence. The process of withdrawing blood, separation of the platelets would definitely pose a risk to both the patient and the practitioner. Especially if the patient is asymptomatic, not warranting a coronavirus test report, then the chances of contracting an infection would be very high. The proximity to the patient required is also more during taking the blood sample and for injecting the platelet-rich plasma into the desired location. Interventional procedures involving the administration of platelet-rich plasma carry a very high risk of injecting viremic plasma. Therefore it is imperative to look at other alternatives.
Pain physicians worldwide use corticosteroids injections commonly for spine interventions, inflammatory arthritis affecting joints, tendons, etc. In spine-related conditions, older population are predisposed to degenerative arthritis involving facet joints, sacroiliac joints and the younger are commonly afflicted with discogenic problems. Deyo observed risks with these injections like infection, injections into the spinal fluid, intravascular injections, nerve damage, hemorrhages, and arachnoiditis. Corticosteroids are associated with different endocrine, metabolic complications. In the current pandemic crisis, the one complication that cannot be overlooked is that of reduction in immune response caused by these injections. This would again amplify the risk of contracting the corona virus infection. Hence a risk-and-benefit ratio should be weighed, specifically the corticosteroid dosage, if they need to be administered, keeping in mind the risk of immunosuppression.
Ozone gas has been used in pain medicine practice for intraarticular injections, intradiscal, periforaminal or intraformational injections. Ozone is inherently bacteriostatic, fungicidal, and virucidal. With these properties, the risk of infection with Ozone is very negligible. Ozone produces acute oxidative stress with a paradoxical anti-oxidant effect. It has been shown that the controlled administration of ozone may promote oxidative preconditioning or adaptation to oxidative stress, which in turn stimulates the anti-oxidant endogenous system, finally resulting in a protective state against tissue damage.
Ozone is also a potent activator of the immune system. Ozone administered at a concentration of between 30 and 55 μg/cc causes the greatest increase in the production of interferon and the greatest output of tumor necrosis factor and IL-2. The production of IL-2 launches an entire cascade of subsequent immunological reactions. Ozone is also easy to generate and does not pose much risk to the patient nor the personnel. All of these factors, coupled with the comparative low cost of ozone make it an attractive alternative option in the present COVID pandemic crisis.
| Conclusion|| |
The world is being crippled by the coronavirus pandemic. As health-care professionals, the best way to protect ourselves against it is by using personal protective measures and following the safety recommendations and guidelines. In the present COVID-19 scenario, as pain specialists, our hands are tied as to which injectable agent to use for different interventions. Ozone therapy has been proven to be safe with encouraging effects in pain control and functional recovery. A few recent studies show that ozone is being employed in the treatment of coronavirus-infected patients with encouraging results. Hence, in the present situation ozone seems to be a better alternative to steroid or platelet-rich plasma injections.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Di Paolo N, Bocci V, Gaggioti E. Ozone therapy editorial review. Int J Artificial Organs 2004;27:168-75.
Bocci V. Biological and clinical effects of ozone: Has ozone therapy a future in medicine? Br J Biomed Sci 1999;56:270-9.
Bocci V. Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases. Med Hypotheses 1996;46:150-4.
Bocci V. Is it true that ozone is always toxic? The end of a dogma. Toxicol Appl Pharmacol 2006;216:493-504.
Holmes J. Clinical reversal of root caries using ozone, doubleblind, randomised, controlled 18-month trial. Gerodontology 2003;20:106-14.
Hernández F, Menéndez S, Wong R. Decrease of blood cholesterol and stimulation of antioxidative response in cardiopathy patients treated with endovenous ozone therapy. Free Radic Biol Med 1995;19:115-9.
Clavo B, Pérez JL, López L, Suárez G, Lloret M, Rodríguez V, et al
. Effect of ozone therapy on muscle oxygenation. J Altern Complement Med 2003;9:251-6.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al
. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8:420-2.
Spychalski P, Błażyńska-Spychalska A, Kobiela J. Estimating case fatality rates of COVID-19. Lancet Infect Dis 2020;20:774-5.
Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al
. Dysregulation of immune response inpatients with COVID-19 in Wuhan, China. Clin Infect Dis 2020;71:762-8.
Tople JP, Das G. COVID-19 and interventional pain practice. J Recent Adv Pain 2020;6:1-3. [Full text]
Rowen RJ, Robins H. A Plausible “Penny” costing effective treatment for corona virus-ozone therapy. J Infect Dis Epidemiol 2020;6:113.
Zamora A, Borrego A, Lopez O, Delgado R, Gonzalez R, Silvia M, et al
. Effects of ozone oxidative preconditioning on TNF-α release and antioxidant-prooxidant intracellular balance in mice during endotoxic shock. Mediators Inflamm 2005;2005:16-22.
Liu Q, Zhou YH, Yang ZQ. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol 2016;13:3-10.
Tetro JA. Is COVID-19 receiving ADE from other coronaviruses? Microbes Infect 2020;22:72-3.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al
. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
Schoeman D, Fielding BC. Coronavirus envelope protein: Current knowledge. Virol J 2019;16:69.
Broer R, Boson B, Spaan W, Cosset FL, Corver J. Important role for the transmembrane domain of severe acute respiratory syndrome coronavirus spike protein during entry. J Virol 2006;80:1302-10.
Sharma VK, Graham NJ. Oxidation of amino acids, peptides and proteins by ozone: A Review. Ozone Sci Eng 2010;32:81-90.
Fernandez-Cuadros ME, Perez-Moro OS, Albaladejo-Florin MJ, Algarra-Lopez R. Ozone Decreases Biomarkers of Inflamation (C-Reactive Protein and Erytrocyte Sedimentation Rate) and Improves Pain, Function and Quality of Life in Knee Osteoarthrtitis Patients: A Before-and-After Study and Review of the Literature, Middle East J Rehabil Health Stud. 2018;5:e64507. doi: 10.5812/mejrh.64507.
Fernandez-Cuadros ME, Perez-Moro OS, Mirón-Canelo JA. Could ozone be used as a feasible future treatment in osteoarthritis of the knee? Divers Equal Heal Care 2016;13:232-9.
Manoto SL, Maepa MJ, Motaung SK. Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis. Saudi J Biol Sci 2018;25:672-9.
Lopes De Jesus CC, Dos Santos FC, De Jesus LM, Monteiro I, Sant'Ana MS, Trevisani VF. Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, doubleblinded, placebo-controlled study. PLoS One 2017;12:1-16.
Mishra SK, Pramanik R, Das P, Das PP, Palit AK, Roy J, et al
. Role of intra-articular ozone in osteo-arthritis of knee for functional and symptomatic improvement. IJPMR 2011:65-9.
Babaei-Ghazani A, Najarzadeh S, Mansoori K, Forogh B, Madani SP, Ebadi S, et al
. The effects of ultrasound-guided corticosteroid injection compared to oxygen–ozone (O2–O3) injection in patients with knee osteoarthritis: a randomized controlled trial. Clin Rheumatol 2018;37: 2517–27. Available from: https://doi.org/10.1007/s10067-018-4147-6
Soltés L, Mendichi R, Kogan G, Schiller J, Stankovska M, Arnhold J. Degradative action of reactive oxygen species on hyaluronan. Biomacromolecules 2006;7:659-68.
Lenhert T, Naguib NN, Wutzler S, Nour-Eldin NE, Bauer RW, Kerl JM, et al
. Analysis of disk volume before and after CT-guided intradiscal and periganglionic ozone-oxygen injection for the treatment of lumbar disc herniation. J Vasc Interv Radiol 2012;23:1430-6.
Gallucci M, Limbucci N, Zugaro L, Barile A, Stavroulis E, Ricci A, et al
. Sciatica: Treatment with intradiscal and intraforaminal injections of steroid and oxygen-ozone versus steroid only. Radiology 2007;242:907-13.
Muto M, Andreula C, Leonardi M. Treatment of herniated lumbar disc by intradiscal and intraforaminal oxygen-ozone (O2-O3) injection. J Neuroradiol 2004;31:183-9.
American Medical Association Morning Rounds, in Affiliation with Bulleting HEALTHCARE, CDC: 25 Dead in Meningitis Outbreak, Cases Reach 337 in 18 States. Monday, October 29, 2012.
Hashemi M, Nabi BN, Saberi A, Sedighinejad A. The comparison between two methods for the relief of knee osteoarthritis pain: Radiofrequency and intra-periarticular ozone injection: A clinical trial study. Int J Med Res Heal Sci 2016;5:539-46.
Sconza C, Respizzi S, Virelli L, Vandenbulcke F, Iacono F, Kon E, et al
. Oxygen ozone therapy for the treatment of knee osteoarthritis: A systematic review of randomized controlled trials. Arthroscopy 2020;36:277-86.