The world, its people and economies have been significantly affected and disrupted by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease (COVID-19) in China at the end of 2019. There has been a great deal of research into stopping its propagation, developing vaccinations and finding effective treatments. Ozone has received a significant amount of attention as a means of stopping its propagation and also in the treatment of COVID-19.
There has been a significant amount of research into how to stop its propagation, vaccinations and treatment. One of the treatments that has received a significant amount of attention is ozone.
What is Ozone?
Ozone is a strong oxidiser which can kill microorganisms and viruses effectively. It has been used for treatment of water and wastewater since the early 1900s. Nikola Tesla patented his first ozone generator in 1896 to produce ozonated olive oil.
Physically and chemically, ozone is an inorganic gas with chemical formula O3. Ozone has a distinctly pungent smell reminiscent of chlorine, with odour threshold between 7 – 20 ppb. Ozone is denser than air and therefore will settle close to the ground in the absence of ventilation.
Some of its key properties include its capacity for disinfection and sanitation (Fig. 1) as well as reducing the microbial load of many microorganisms (Fig. 2).
How can Ozone be effective against the SARS-CoV-2 virus and COVID-19?
Ozone has proven to be extremely effective at killing bacteria, molds, fungi and viruses as it is a strong oxidizer. However, this same property also makes ozone a hazard to human health at concentrations as low as 60 ppb. Hence it must be handled with care.
It is equally important to combat the virus both inside the human body as well as in the environment. These viruses, being RNA viruses, are found to be susceptible to ozone. Ozone being an unstable molecule can breakup into its split products namely reactive oxygen species and ozonides creating a toxic environment for these viruses. Ozone mainly prevents the membrane fusion with the host cell, thus interfering with their replication. With such vast applications of the gas, it has created a new spark in the field of medicine in combating these viruses and many other organisms. Two of the key applications of ozone are: sterilization and patient treatment.
Ozone can be used in the disinfection of viral contaminated environments. Its maximum anti-viral efficacy requires a short period of high humidity (>90% relative humidity) after the attainment of peak ozone gas concentration (20 25 ppm, 39-49 mg/m3 ). As a gas it can penetrate all areas within a room, including crevices, fixtures, fabrics, hospital room, public transport, hotel room, cruise liner cabin, office, etc. and under surfaces of furniture, much more efficiently than manually applied liquid sprays and aerosols. The environment to be treated must be free of people and animals due to the relative toxicity of ozone via inhalation.
If fact, some studies such as one at Fujita Health University in Japan found that even lower concentrations were sufficient. They found that ozone gas in concentrations of 0.05 to 0.1 ppm, levels considered harmless to humans, could kill the virus.
Stopping the spread of COVID-19
Sanitizing our homes, workplaces and public spaces is a key tactic in the fight against Coronavirus, to stop the spread of COVID-19. Ozone sterilization is also commonly used in hospitals to sanitize equipment and significantly reduce or eliminate the spread of bacteria.
During the SARS epidemic of 2003, ozone sterilization was successfully used to purify environments infected with the deadly Coronavirus, SARS-CoV-1, the virus which causes SARS disease. SARS-CoV-2 is a member of the same Coronavirus family. A number of studies and tests conclude that ozone does kill envelope viruses including members of the virus family coronaviridae (like MERS-CoV, SARS-CoV-1 and SARS-CoV-2).
Ozone destroys this type of virus by breaking through the outer shell into the core, resulting in damage to the viral RNA. Ozone can also damage the outer shell of the virus in a process called oxidation.
Put simply, exposing Coronaviruses to sufficient ozone dose (ppm x time) can result in them being 99% damaged or destroyed.
An important consideration in the use of gaseous ozone for disinfection of premises is the half-life of ozone, which will affect its effectiveness and safety protocol.Its half-life ranges from several hours in a sealed plexiglass cylinder 5 to 11 mins in an office environment with recirculating air and temperature between 21 – 27 °C and relative humidity of 26 – 50%.
Ozone as a treatment
As ozone is a gas and also unstable, it is not easy to apply or administer. The development of Ozonated (or Ozonized / Ozonised) Oil (HOO) solved this problem making ozone highly stable and bioavailable due to its bond with the lipid carrier. Ozonated Oil administration is totally noninvasive occurring by oral administration of pills or as nasal spray.
Ozonated Oil administration can be proposed as complimentary therapeutic treatment for COVID-19 infections, without the need for any modifications of the established standard therapeutic protocols. This complimentary treatment could be helpful to:
- decrease the severity of the diseases lowering the number of COVID-19 patients requiring high-intensity therapies;
- fasten qPCR negativization after disease and time-span of hospital recovery.
Ozone´s mechanism of action against the SARS-CoV-2 virus
In general, systemic ozone therapy can be potentially useful against SARS-CoV-2. The rationale and mechanism of action has already been proven clinically in other viral infections and has been shown to be highly effective in a number of research studies.
The mechanism of action is by:
- The induction of adaptation to oxidative stress, hence a re-equilibration of the cellular redox state
- The induction of IFN-gamma and proinflammatory cytokines
- The increase of blood flow and tissue oxygenation to vital organs
- It has the potential actions to act as an auto-vaccine when administered in form of minor autohemotherapy
The recommended routes of administration are.
- Major Autohemotherapy (MAH),
- Ozonized Saline Solution (O3SS),
- Extracorporeal Blood Oxygenation-Ozonation (EBOO)
- and a variant of the Minor Autohemotherapy (MiAH)
Treating COVID-19 patients
A treatment with ozone is of significant interest in the treatment of COVID-19 patients because:
- It has an immunological role within SARS-CoV-2 regimens, because of the modulation of cytokines and interferons, including the induction of gamma interferon.
- Ozone exerts antiviral activity through the inhibition of viral replication and direct inactivation of viruses.
- Ozone is an antiviral drug enhancer and is not an alternative to antiviral drugs.
- Combined treatment with involving ozone and antivirals demonstrated a reduction in inflammation and lung damage.
Severe forms of COVID-19 can evolve into pneumonia, featured by acute respiratory failure due to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In viral diseases, the replication of viruses is seemingly stimulated by an imbalance between pro-oxidant and antioxidant activity as well as by the deprivation of antioxidant mechanisms. In COVID-19 pneumonia, oxidative stress also appears to be highly detrimental to lung tissues. Although inhaling ozone (O3) gas has been shown to be toxic to the lungs, recent evidence suggests that its administration via appropriate routes and at small doses can paradoxically induce an adaptive reaction capable of decreasing the endogenous oxidative stress. Ozone therapy is recommended to counter the disruptive effects of severe COVID-19 on lung tissues, especially if administered during the early stages of the disease, thereby preventing the progression to ARDS.
In other tests, patients with COVID-19 with mild to severe symptoms who received intravenous O3SS as an adjunct treatment experienced no side effects The main results of O3SS treatment were a tendency to improve clinical symptoms without side effects None of the patients treated died
Ozone treatment has also been shown in research studies to be highly effective at decreasing organ damage mediated by inflammation and oxidative stress from viral infections.
- World Health Organization, COVID-19 global literature on coronavirus disease
- Schwartz, A.; Martínez-Sánchez, G.; de Lucía, A. M.; Viana, S. M.; Constanta, A. M., “Complementary application of the ozonized saline solution in mild and severe patients with pneumonia COVID-19: A non-randomized pilot study”, Journal of Pharmacy and Pharmacognosy Research ; 9(2):126-146, 2021. WHO COVID, ID: covidwho-984802
- Martínez-Sánchez, Gregorio; Schwartz, Adriana; Donna, Vincenzo Di, “Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19”, Antioxidants (Basel) ; 9(5)2020 May 06. ID: covidwho-854062
- International Scientific Committee of Ozone Therapy, “Potential use of ozone in SARS-CoV-2 / COVID-19”, ID: grc-743616.
- Cristiano L. “Could ozone be an effective disinfection measure against the novel coronavirus (SARS-CoV-2)?” J Prev Med Hyg. 2020 Oct 6;61(3):E301-E303. doi: 10.15167/2421-4248/jpmh2020.61.3.1596. PMID: 33150218; PMCID: PMC7595067.
- Siddharta A, Pfaender S, Vielle NJ, Dijkman R, Friesland M, Becker B, Yang J, Engelmann M, Todt D, Windisch MP, Brill FH, Steinmann J, Steinmann J, Becker S, Alves MP, Pietschmann T, Eickmann M, Thiel V, Steinmann E. “Virucidal Activity of World Health Organization-Recommended Formulations Against Enveloped Viruses, Including Zika, Ebola, and Emerging Coronaviruses”. J Infect Dis. 2017 Mar 15;215(6):902-906. doi: 10.1093/infdis/jix046. PMID: 28453839; PMCID: PMC5407053.
- Cattel F, Giordano S, Bertiond C, Lupia T, Corcione S, Scaldaferri M, Angelone L, De Rosa FG. “Ozone therapy in COVID-19: A narrative review”. Virus Res. 2021 Jan 2;291:198207. doi: 10.1016/j.virusres.2020.198207. Epub 2020 Oct 25. PMID: 33115670; PMCID: PMC7585733.
- Swift R, “Japan researchers say ozone effective in neutralising coronavirus”, 26Aug20, Reuters,
- Morteza Izadi, Luca Cegolon, Mohammad Javanbakht, Ali Sarafzadeh, Hassan Abolghasemi, Gholamhossein Alishiri, Shi Zhao, Behzad Einollahi, Mandana Kashaki, Nematollah Jonaidi-Jafari, Mosa Asadi, Ramezan Jafari, Saeid Fathi, Hassan Nikoueinejad, Mehrdad Ebrahimi, Sina Imanizadeh, Amir Hosein Ghazale, “Ozone therapy for the treatment of COVID-19 pneumonia: A scoping review”, International Immunopharmacology, Volume 92, 2021, 107307, ISSN 1567-5769,