The novel corona virus disease 2019 (COVID-19) outbreak has created a global dramatic pandemic with a significant morbidity and mortality rate and a huge clinical and economical impact on our lives. Considering the massive health and economic burden of the pandemic, any means by which to improve and accelerate the recovery of the patients and to reduce the risk of death would be considered of great significance. Thereby focusing on the existing therapies; here we focus on one of the most extensively studied, Ozone therapy.

Ozone is a colourless gas, made up of 3 atoms of Oxygen. Ozone Therapy has been used since the early 19thcentury, but little is known about it. The therapy involves the process of administeringa mixture of ozone and oxygen (Medicated Ozone)into the body in order to treat an infection or wound. Medical Ozone contains a maximum concentration of less than 5% of Ozone and the rest is pure medical oxygen.

Previously, this therapy has proven to be a successful aid in the treatment of chronic pain management, immune disorders, Diabetes Mellitus, Breathing disorders such as COPD, and even in a few viral and bacterial disorders such as HIV and cellulitis respectively

Biological and therapeutic effects of ozone:

Ozone, when administered, dissolves in plasma and reacts with several biomolecules such as reactive species of oxygen(ROS) and lipid oxidation products(LOP) which are also known as the “ozone messengers”.

O3 + Biomolecules → O2 + O

Here, the atomic oxygen acts as a very reactive atom. Ozone reacts with polyunsaturated fatty acids (PUFA), antioxidants like ascorbic acid, thiol compounds with sulfhydryl containing groups (-SH) like cysteines and albumin. Based upon the administered dose of Ozone, carbohydrates, enzymes, DNA and RNA are also affected as they all act as electron donors and undergo oxidation. Ozone modulates inflammation and oxidative stress, stabilizing the pro-oxidant and antioxidant balance.

Mechanism of oxidation: Please check image below

Antiviral characteristics of ozone:

Corona viruses are large RNA viruses, spherical in shape, from which protrude corona-shaped (crown shaped) spicules (S-protein, made up of cysteine and tryptophan). In 21stcentury, three new Corona Virus have appeared whose pathogenicity is more serious and causes severe acute respiratory syndrome (SARS), which are SARS-CoV , MERS-CoV (Middle East Respiratory syndrome), and SARS-CoV-2.

Ozone, being the most powerful oxidant found in nature, exerts high oxidizing effects.

In viruses, their viral capsid is damaged by ozone which in turn disturbs its reproductive cycle and disrupts the virus-cell contact by the process of peroxidation. Cells contain weak enzyme coatings which make them highly vulnerable to viral invasion. These are highly susceptible to oxidation, and thus eliminated from the body, which is later replaced with healthy cells.

Method of administration of ozone:

Ozone therapy combines a mixture of oxygen (O2)-O3, with a diverse therapeutic range (10–80 μg/ml of gas per ml of blood).

Ozone can be administered by VARIOUS routes:

· systemic (major autohemotherapy (AHT), saturated saline solution, rectal and vaginal insufflation)

Major AHT is a process where 100-150ml of venous blood is derived from the patient and the blood is mixed with Medical Ozone in required therapeutic doses along with anticoagulants such as Heparin or 3.13% Natrium Citrate solution and reinfused back to the patient.

· non-systemic technique (minor autohemotherapy and bag ozone therapy)

In Minor AHT, 5-10ml of blood is mixed with a precise dose of MO and reinfused/reinjected intramuscularly to the patient without any anticoagulants.

In spite of the ozone therapy being quite safe and promising and cost effective, there are only 3 ongoing clinical trials in China based upon this therapy.

We have seen how ozone therapy can be helpful in treating every stage of COVID 19. Given the urgency of the pandemic, it is high time that more experimental studies are conducted on this therapy and thus include it in the conventional therapy of COVID 19.

Based upon the already available data, Ozone therapy can also be used as a supportive care in order to increase the patient’s quality of life and reduce the overall duration of the therapy.