COVID-19, MERS, SARS and
Other Emerging Coronaviruses: Theoretical Considerations
and a Proposal for Critical Care
Parenteral Blood Ozonation

This article was originally published in May 2013, under the title: “MERS, SARS, and Emerging Coronaviruses: Theoretical Considerations and a Proposal for Critical Care Parenteral Oxygen/Ozone Therapy”

The present article has been updated to reflect the worldwide emergence of Covid-19 Articles on the science of medical ozone technology may be accessed on: ozoneinmedicine.com

The author is former President and Director of Research for Medizone International, Inc., a public company centered on the development and research of oxygen/ozone based technologies to inactivate ozone-sensitive microbes. Applications include the disinfection of ambient spaces, including hospital milieus, the sterilization of medical equipment, and the resolution of wounds derived from diabetes and vascular insufficiency that all too often lead to limb amputations. In this paper, the author discusses the possibility of using oxygen-ozone mixtures to decrease blood viral loads in infections such as Covid-19.

Abstract

The Coronavirus family catalogs an expanding population of members. To the respectable number of animal coronaviruses, seven human coronaviruses have been identified, most producing mild transitory malaise syndromes. The last three emergent family members, however, stand out by their increased capacity to spawn significant human illnesses. Furthermore, the latest arrival, Covid-19, has remarkably advanced the challenges of Coronaviridae by perfecting human-to-human transmission, and by bolstering its lethality.

Covid-19 isthe newest member of the Coronaviridae family of viruses and is the third coronavirus crossing animal species barriers to infect human populations. The previous two members of the family are the Severe Acute Respiratory Syndrome coronavirus, SARS-CoV, emerging in 2002, and the Middle East respiratory syndrome coronavirus, MERS-CoV, in 2012. All can cause severe, even fatal cardiopulmonary stress.

SARS is a disease presenting significant malignancy. Among its animal reservoirs are civet cats and bats. Capable of commanding massive public health importance because of the unpredictability of its demographic cycles, SARS presents supremely challenging problems in light of its high mutational thrust.

MERS (Middle East Respiratory Syndrome) belongs to the same Family as SARS and is more recent arrival on the world stage (2012). Much uncertainty remains as to its modes of transmission and the identity of its animal reservoirs, although dromedary camels have been solidly implicated. MERS’ dangerousness has been well established.

Covid-19 attests to the high mutational capacities of Coronavirus family members. By extending their reservoir range to include other animal species (such as pengolins), by delaying the onset of symptoms while maintaining infectivity, and by further mastering human-to-human transmission and expanding vectoring routes to include droplet, oral-fecal and body fluids modes (Wei 2020), Covid-19 viruses greatly expand their capacity to create epidemics and pandemics.

As with many viruses, coronaviruses have complex host invasion, replication and transmission cycles. A crucial replication phase, known as the viremic phase, involves the explosive reproduction of viral particles, virions, exiting from infected and dying host cells, disgorging daily billions of viral progeny into all manner of bodily fluids. Indeed, in these massive seedlings, all organs are suddenly virally overwhelmed, and existentially challenged.

The present thesis proposes one method for reducing coronavirus blood stream onslaughts. Since normal T-cell activation will be sluggish due to the body’s naiveté relative to Covid-19 antigens and will consequently have delayed response times, reduction of viral load is posited to offer a plausible emergency viral abatement strategy.

Ozone, because of its special biological properties, has theoretical and practical attributes to make it a viable candidate as a Covid-19, MERS and SARS viral load-culling agent. The key to this strategy is embodied in coronaviral vulnerability to oxidizing agents due to the fragility of their lipid-rich envelopes.

The technology of interfacing oxygen-ozone gas mixtures with bodily fluids has long been mastered (Rilling 1985, Viebahn 2007, Bocci 2013, DiPaolo 2005, Smith 2017), and finds support in the vast scientific literature dating well into the 19th century on the chemical, biochemical, immunological and otherwise physiological effects of ozone on bodily systems, all woven with ever-deeper understanding of the role of oxygen and reactive oxygen species (ROS) in metabolic redox reactions. A proposal is herewith made for the further study of parenteral administration of calibrated oxygen/ozone gaseous mixtures in the critical care of Covid-19, SARS and MERS, and in the upcoming new infections that, given time and the nature of these viruses, will inevitably arrive.

This can be achieved via a number of technologies that have long been the purview of pioneer physicians. Most experience has been gleaned from methods utilizing the serial treatment of blood aliquots with oxygen/ozone gaseous mixtures, known as autohemotherapy (AHT). More comprehensive methods, although more sophisticated but ones that have greater potential to succeed in Covid-19 culling, involve the treatment of the total blood and lymph volumes via techniques called Extracorporeal Blood Oxygenation Ozonation -EBOO (Bocci 2002; Di Paolo 2000).

Reluctant to use the term “viral intelligence” to refer to coronaviral adaptability and creativity, there is equal controversy for defining viruses’ existence as life forms. How, we may ask, can viruses deserve such appellation when, in fact, they use Machiavellian strategies to hijack the genetic integrity of bona fide life forms, such as us humans, and thus assume roles of ultimate parasites?

The Family of Coronaviruses

Covid-19, SARS and MERS viruses belong to the viral family, Coronaviridae, that includes two genera, coronavirus and togovirus, each showing similar yet distinct architecture, replication mechanisms and genomic organization. First identified in the 60’s, this family identifies itself by large, lipid-enveloped, positive-stranded RNA virions. Their appearance is distinct, with envelopes endowed with spikes, or peplomers, capable of attaching to host cells, thus initiating their viral invasive attack. The large, amply spaced petal-shaped peplomers on the virions’ surface give them a crown-like appearance, possibly branding themselves as the new royals of the greater virus universe.

Widely seen in nature, coronaviruses infect a spectrum of animal hosts and are responsible for avian infectious bronchitis, murine hepatitis, and porcine gastroenteritis, among others. Of likely significance to humans is that animal coronaviruses are able to cross into their central nervous systems.

Prior to SARS and MERS, Coronaviridae were responsible for relatively mild cold-like syndromes in humans corresponding to their predilection for the ciliary epithelium of the trachea, nasal mucosa, and lung alveolar cells. At times they were rarely implicated in serious respiratory illnesses in frail older adults (Falsey 2002), and in some cases of infant diarrhea.

Virion architecture and molecular biology

The SARS virion differs from other members of the Coronaviridae family in its genomic composition. The other viral structures, including Covid-19, however, follow family virion architecture and the composition of their structural proteins.

The software for viral replication is the nucleic acid core, a single strand long- chain RNA nucleotide. The core is surrounded by the nucleic acid coat, or capsid. The rigid capsid, made of repeating units called capsomeres, determines the shape of the virus.

Envelopes forming the outer layer of virions are formed at the time of viral budding, an intricate process in which nucleocapsids exit host cells to infect others. Fusing with host cell membranes, usurp their lipoproteins to form proprietary envelopes. The lipid composition of viral membranes reflects the lipid composition through which the particles exit. This fact is important for understanding the treatment strategy herewith advanced.

Coronavirus envelopes are composed of lipid bilayers associated with a union of carbohydrates and proteins, glycoproteins, and lipids and phosphates, phospholipids. Up to 60% of the lipid component of the envelope contains phospholipids and the remainder is mostly cholesterol. This envelope is closely articulated with the peplomers, which determine attachment and penetration into host cells.

The genome composition and sequence of the SARS virus has been identified (Marra 2003, Rota 2003). Marra et al. described a viral genome configuration of 29,727 nucleotides in length, within which exists a gene order similar to other coronaviruses. However, because the genetic composition of SARS does not closely resemble any of the three known species of coronaviruses, they propose a new and fourth class of coronaviruses, the SARS-CoV. In the creation of Covid-19, it is postulated, in one hypothesis, that an animal virus recently mutated to successfully infect humans,

Coronavirus structural proteins include the N nucleocapsid phosphoprotein which binds to viral RNA; the membrane glycoprotein M that forms the shell of the internal viral core is responsible for triggering viral assembly; protein E is associated with the virion envelope; the spike glycoprotein S binds to specific cellular receptors and elicits cell-mediated immunity; and the hemaglutinin-esterase glycoprotein HE forms spikes on the coronavirus envelope (Knipe 2013).

Coronavirus replication

The viral replication cycle follows the general pattern seen in mammalian viruses and may be divided into several stages (Cann 1997; Evans 1997; Knipe 2013). The coronavirus attaches to the membrane of the host cells by binding the S and HE proteins of its peplomers to host receptor glycoproteins or glycans.

Once host cell entry is achieved, the virion sheds its envelope to commence its replication in the host cytoplasm. It binds to cellular ribosomes, and its released viral polymerases begins the RNA replication cycle. Newly formed viral nucleocapsids continue their assembly with the acquisition of new envelopes by means of budding through membranes of host cells’ endoplamic reticulum. Virions are then released into the general blood and lymphatic circulations, ready to infect new cells, other organ systems, and eventually, in human-to-human transmission, new hosts.

SARS: Clinical findings

The clinical manifestations of SARS have been comprehensively described (Peiris 2003). In this study of 50 hospitalized patients, fever, chills, myalgia, and dry cough were the most frequent presenting complaints. Also reported, were rhinorrhea, sore throat, and gastrointestinal symptoms. Radiological examination showed evidence of pulmonary consolidation some 5 days after the onset of symptoms. Laboratory examination showed leucopenia and lymphopenia, despite the presence of fever; also anemia, thrombocytopenia, liver enzyme elevations (alanine aminotransferase), and skeletal and heart muscle enzyme elevation (creatinine phosphokinase). All these features point to severe systemic inflammatory insults.

The incubation of SARS is 2 to 10 days, and in some patients perhaps longer. The respiratory route achieves viral transmission where it may infect new hosts through aerosol and droplet contact with mouth mucosal surfaces, nose, throat, and likely the conjunctiva. SARS virions have been found in feces and the importance of this route of transmission is being evaluated, as it is known that several animal coronaviruses use this propagation venue. Moreover, since it is appreciated that SARS particles remain viable on objects for 48 hours or longer, any eradication effort must address the infectivity of fomites in the environment.

The SARS syndrome can progress to severe disease with respiratory distress and oxygen desaturation requiring ventilatory support in over a third of patients, approximately 8 days after symptom onset. Mortality has been noted to vary according to transmission clusters, ranging from 3% to 20%. This suggests that the evolution of SARS depends upon a heterogeneous population of viral quasispecies with variable degrees of virulence.

COVID-19: Clinical manifestations and therapy – and a proposal

Covid-19’s clinical course has been described in patients in Wuhan, China. As of this writing, a sampling of some 45,000 Covid-19 patients yielded a tally of 80% with only mild symptoms; 20%, however, showed various degrees of physical insult, some showing multiple organ failure, reaching levels requiring cardio-respiratory assistance. Among them, 2.3 % died – closely equivalent to the 1918 epidemic (Report, The New York Times, Feb 29, 2020, Michael Barbaro, “Inside the Times”).

Chen et al. (2020) described the clinical features of 99 cases of Covid-19. Among them, 83% had fevers, 82% cough, 31% shortness of breath. A spectrum of other symptoms included headache, muscle ache, confusion, chest pain, diarrhea, and sore throat; 17% had multiple organ damage and 4% septic shock.

Treatment was supportive with 75% receiving oxygen, 19% glucocorticoids, IV immunoglobulins, and 25% received antibiotics for secondary infections.

Note: Interestingly, 3%were treated with extracorporeal membrane oxygenation (ECMO). This technique that began development in the 50’s, in response to the need for blood oxygenation during cardiac interventions, is now seeing rapid progress with use in clinical emergencies, including in infants.

Acute Covid-19 patients are stressed by both blood gas challenges and viral attacks. Blood oxygen falls while blood carbon dioxide levels becomes toxic. At the same time, Covid-19 waves persist in their assaults. Could ECMO treatment be improved so that, with ozone-adapted machinery and membranes, minuscule, yet carefully calibrated concentrations of oxygen-ozone are added to the gas mixture in order to assist blood oxygenation, carbon dioxide removal, and the reduction of viral load?

There are currently neither vaccines nor antiviral agents available for Covid-19, SARS or MERS, only supportive and often intensive measures to maintain physiological homeostasis. Antiviral agents and inhibitors to inflammation (steroids, NSAIDS) have, thus far, not been effective in significantly softening the virulence of Covid-19, SARS nor MERS.

COVID-19, SARS and MERS: Genetic creativity

As is the case in most RNA viruses, coronaviruses mutate at a high rate (Steinhauer 1986). Within any one afflicted individual, coronaviruses particles do not show a homogeneous population. Instead, they function as a pool of genetically variant quasispecies. This is due to the high error frequency of RNA polymerases, the presence of deletion mutants, the high frequency of RNA recombination and point mutations, and the occurrence of defective-interfering RNA (DI RNA).

Some of the Covid-19 quasispecies will find themselves at an advantage in countering host antibody responses and pharmacological measures. They will propagate accordingly, thus expanding their ecological terrain. Other genetic creations will be too lethal to their hosts, thus working against their own survival. If we can speak of a viral psychology, an efficient survival balance aims somewhere between viral survival with mild symptomatology and aggressive propagation with eventual viral suicide through enhanced lethality.

Ozone: Physical and physiological properties

The oxygen atom exists in nature in several forms:

• As a free atomic particle (O), normally produced in the course of metabolism, is highly reactive and unstable. Exogenous anti-oxidants are sometimes used to temper its metabolic effects.
• Oxygen (O2), its most common and stable form, is colorless as a gas and pale blue as a liquid. In its ability to give up one of its atoms and accept electrons in return, it drives numerous metabolic reactions.
• Ozone (O3), distinctly blue as a gas and dark blue as a solid, has a molecular weight of 48, a density one and a half times that of oxygen, and contains a large molecular energy excess (O3 → 3/2 O2+ 143 KJ/mole), which can be imparted to many other molecules. Its bond angle of 127 ± 3°, resonates among several forms
• O4 is a very unstable, rare, nonmagnetic pale blue gas formed at the interface of earth’s stratosphere’s outer layer where the sun’s radiation first encounters earth. O4 readily breaks down to two molecules of oxygen.

Ozone (O3), a naturally occurring configuration of three oxygen atoms, has a half-life of about one hour at room temperature, reverting to oxygen. A powerful oxidant, ozone has unique biological properties. Since some ozone-based therapies are administered by interfacing gaseous oxygen/ozone with blood, basic research on ozone's biological dynamics have often centered upon its effects on blood cellular elements (erythrocytes, leucocytes, and platelets), and on its serum components (proteins, lipids, lipoproteins, glycolipids, carbohydrates and electrolytes).

The effects of ozonation on whole blood are extraordinarily complex and are far from adequately elucidated. Indeed, ozone can react with serum proteins, including enzymes, immunoglobulins, clotting factors, hormones, vitamins, lipoproteins and cholesterol, carbohydrates including glucose and electrolytes, among others (Dailey 1998). Comparing blood to an orchestra, ozone administration can be likened to the introduction of a novel and powerful musical instrument, affecting the interactions of all others.

Even though an in-depth analysis of ozone’s multifaceted effects upon the panoply of blood constituents is beyond the intent and scope of this article (The reader is referred to Bocci 2002; Smith 2017), the following points of research are significant.

Erythrocytes have been extensively studied in relation to ozone administration. Many studies that have used erythrocyte suspension in physiologic saline (Kourie 1998; Fukunaga 1999) have found hemolysis at relatively low ozone dosages (10 to 30 ug/ml). When ozone is administered in whole blood, however, the dynamics of ozone interaction are such that hemolysis begins to be observed at significantly higher doses, implying a buffering action of blood constituents. Moreover, the functionality of erythrocyte enzymes is maintained, suggesting a protective role of blood’s antioxidant systems (Cross 1992). There is some evidence that low-dose ozone administration may stimulate erythrocyte formation and release (Hernandez 1999).

Leucocytes, intimately connected to immune function, show good resistance to ozone because, unlike viruses, they possess enzymes that protect them from oxidative confrontation. These enzymes include superoxide dismutase, glutathione, and catalase. A promising area of research centers on cytokine and interferon stimulation in ozone administration and its implication for enhancing immune function (Paulesu 1991; Bocci 1994; Larini 2001). A classical adage of ozone therapy is that lower ozone dosages are stimulating to immune action while higher dosages become inhibitory (Viebahn 1999). Further research will need to clarify the parameters of this phenomenon, as well as the effects of ozone infusion upon different types of leucocytes in relation to the disease under treatment.

Ozone: Antipathogenic properties

Recently, there has been renewed interest in the potential of ozone for viral inactivation in vivo. It has long been established that ozone effectively works against the viability of bacteria, viruses, fungi, and parasites in aqueous media. This has prompted the creation of water purification processing plants in now hundreds of major municipalities worldwide (e.g., Los Angeles, Paris, Moscow). Ozone’s unique physicochemical and biological properties and its environmentally-friendly features, have since been applied to a panoply of industrial uses such as the packaging of pharmaceuticals, the treatment of homes and buildings (sick building syndrome), the treatment of indoor air in operating theaters and nursing homes, and the disinfection of large-scale air conditioning systems in hospitals.

Ozone’s remarkable capacity for pan-antipathogenic action have been applied to the treatment of poorly healing wounds and burns (Viebahn 2007, Bocci 2013, Sunnen 2009).

A partial list of organisms susceptible to ozone inactivation in these clinical situations includes all those commonly contaminating all manner of wounds, both aerobic and anaerobic bacteria, Bacteroids, Campylobacter, Clostridium, Corynebacteria, Escherichia, Klebsiella, Legionella, Mycobacteria, Propriobacteria, Pseudomonas, Salmonella, Shigella, Staphylococcus, Streptococcus, and Yersinia.

Ozone-susceptible viruses include Adenoviridae, Filiviridae, Hepnaviridae, Herpesviridae, Orthomyxoviridae, Picornaviridae, Reoviridae, Retroviridae and Coronaviridae.

Ozone-sensitive fungi include Actinomycoses, Aspergillus, Candida, Cryptococcus, Epidermophyton, Histoplasma, Microsporum, and Trichophyton, among others.

Some viruses are more susceptible to ozone's action than others. It has been found that lipid-enveloped viruses are the most sensitive. This makes intuitive sense, since enveloped viruses are designed to blend into the dynamically constant milieu of their mammalian hosts. This group includes, hepatitis B and C, herpes 1 and 2, Cytomegalus (Epstein-Barr), HIV 1 and 2, Influenza A and B, West Nile virus, Togaviridae, Eastern and Western equine encephalitis, rabies, and Filiviridae (Ebola, Marburg), among others. Prominently, are all Coronaviridae family members, including Covid-19, SARS and MERS.

The envelopes of viruses provide for intricate cell attachment, penetration, and cell exit strategies. Peplomer crowns, finely tuned to adjust to changing receptors on a variety of host cells, constantly elaborate slightly new glycoprotein configurations under the direction of the viral genome, thus adapting to host cell defenses. Lipid-enveloped viruses leave their coats on entering cells, replicate by hijacking host genetic integrity, then exit surreptitiously though host cell membranes donning usurped fashionable new garments. But lipid coats and envelopes are fragile; they are easily oxidized and destroyed by ozone’s actions.

Lipid-enveloped viruses in aqueous media are readily inactivated by ozone via the oxidation of their envelope lipoproteins and glycoproteins (Akey 1985; Shinriki 1988; Vaughn 1990; Wells 1991; Carpendale 1991). In whole blood, however, ozone’s virucidal actions are buffered by the spectrum of its components and ozone becomes less effective. This situation is further complicated in the case of retroviruses which ensconce themselves within host DNA (Chun 1999), and in Herpesviridae, where virions have the capacity to persist indefinitely in their hosts through the formation of episomes in the nuclei of the cells that harbor them (White 1994).

Several studies have reported the safety and the benefits of ozone administration in vivo. Wells et al. (1991) showed that ozone-treated HIV-spiked Factor VIII maintained its biological capacity, and that, concomitantly, there was an 11-log reduction in virion presence.

The improvement of liver enzymes in hepatitis C patients after several months of ozone therapy was described (Viebahn 1999; Amato 2000). An 80% hepatitis C viral load reduction in 82 patients using AHT was also reported (Luongo et al., 2000). It is remarkable, however, that to date, no adequate double-blinded study has addressed ozone therapy in viral conditions such as hepatitis B and C, HIV, or herpes, all long-time afflictors of humans..

Ozone: Clinical methodology

Ozone may be utilized for the therapy of a spectrum of clinical conditions (Viebahn 2007, Bocci 2013) and may involve external and internal applications. Most promising are externally-applied oxygen/ozone gas mixtures for the resolution of diabetic and vascular skin ulcers that are notoriously difficult to heal and all too often result in limb amputations (Sunnen, USPTO patent # 6,073,627, “Apparatus for the application of ozone/oxygen for the treatment of external pathogenic conditions.”

In the technique of ozone autohemotherapy (AHT), an aliquot of blood (50 to 500 ml) is withdrawn from a virally afflicted patient, anticoagulated, interfaced with a calibrated ozone/oxygen mixture, then reinfused. This process is repeated serially, in a manner consonant with treatment protocols until viral load reduction and symptom abatement are observed.

Another, more experimental and more intensive technique of oxygen/ozone gas administration, is called Extracorporeal Blood Oxygenation Ozonation (EBOO), which treats the entire blood volume using an ozone-resistant hollow-fiber oxygenator-ozonizer, much in the model of dialysis intervention (Bocci 2013, Di Paolo 2005). Bocci describes the caveats in using this method, not the least of which involves problems interfacing complex biomechanical machinery with a lethal agent. Given human ingenuity, however, these problems are solvable.

This and similar methods are likely to be the most efficient in culling the massive virion waves that viremic episodes spawn. For the present time, however, AHT offers simpler - yet totally un-researched in Covid-19 - interventions that involve only one venipuncture per treatment (while EBOO requires two). Research is first needed to gauge EBOO’s viral culling action in innocuous Covid-19 surrogates.

Ozone: Possible Mechanisms of Anti-Viral Actions

The average adult has 4 to 6 liters of blood, accounting for about 7% of body weight. How can any viral load reduction reported via ozone therapies be explained in the face of a technique that treats relatively small percentages of blood volume, as in AHT, albeit serially? Would not more comprehensive approaches, that recruit the entire blood and lymph volumes, much as in dialysis, be more efficient in Covid-19 virion harvesting? All is fodder for research, yet several theoretical bases for blood-to-oxygen/ozone interfacing suggest that the viral culling effects of ozone in infected blood may recruit a variety of mechanisms. Research is needed to ascribe relative importance to each of these, and possibly other mechanisms accounting for ozone’s anti-viral actions:

• The denaturation of virions through direct contact with ozone. Ozone, via this mechanism, disrupts viral proteins, lipoproteins, lipids, glycolipids, and glycoproteins. The presence of numerous double and triple chemical bonds in these molecules makes them vulnerable to the oxidizing actions of ozone’s molecule, which readily donates its oxygen atom and accepts electrons in redox reactions. Unsaturated chemical bonds are thus reconfigured, viral molecular architecture is disrupted, and breakage of the envelope ensues. Deprived of an envelope, virions cannot sustain nor replicate themselves.
• Ozone proper, and the peroxide compounds it creates, may alter structures of the viral envelope that are necessary for attachment to host cells. Peplomers, the viral glycoproteins protuberances that connect to host cell receptors, are posited to be likely sites of ozone action. Even minimal alterations in peplomer integrity through lipoprotein peroxidation could impair attachment capability to host cellular membranes, thus foiling viral attachment and penetration.
• Introduction of ozone into the serum portion of whole blood induces the formation of lipid and protein peroxides. While these peroxides are not toxic to the host in quantities produced by ozone therapies, they nevertheless possess oxidizing properties of their own which persist in the bloodstream for up to several hours. Peroxides created by ozone administration show long-term antiviral effects that may serve to further reduce viral load.
• The immunological effects of ozone have been documented (Bocci 2013; Paulesu 1991; Smith 2017). Cytokines, proteins manufactured by several types of cells, regulate the functions of other cells. Mostly released by leucocytes, they are important in mobilizing immune reactivity. Ozone-induced release of cytokines may constitute an avenue for the reduction of circulating virions.
• Ozone’s actions on viral particles circulating in infected blood yield several possible outcomes. One outcome is the modification of virions so that they remain grossly structurally intact yet sufficiently dysfunctional as to be nonpathogenic. This attenuation of viral particle functionality through slight modifications of the viral envelope, and possibly the viral genome itself, not only modifies pathogenicity, but also allows the host to diversify its immune response. The creation of dysfunctional viruses by ozone offers novel therapeutic possibilities. In view of the fact that so many mutational variants exist in any one afflicted individual, the creation of an antigenic spectrum of crippled virions could provide for a unique host-specific stimulation of the immune system, thus designing what may be called a host-specific autovaccine.
• A exciting research thrust suggests that the virucidal properties of antibodies are predicated upon their ability to catalyse highly active forms of oxygen including ozone (Max 2002; Wentworth 2002). A key element in the microbe-inactivating capacity of antibodies may thus reside in the formation of ozone and other oxygen reactive species (ROS) integral to antigen-antibody reactions. Indeed, according to these revolutionary findings, the very crux of our human defense against microorganisms may reside in our capacity to produce endogenous ozone and ROS. Exogenously administered ozone may, in this model, add to the efficacy of the body’s antigen-antibody dynamics.

COVID-19, MERS, SARS, and Ozone: The future of research

Covid-19, MERS and SARS are produced by novel coronaviruses that have succeeded in breaching the immunological defenses of our contemporary human populations. They appear to have developed an uncomfortable balance between viral propagation, and lethality.

A universal strategy in mastering infections, whether bacterial or viral, is the body’s culling of pathogenic organisms to the point where they no longer represent an invasive and replicative threat. This may be achieved by responsive systems of host immune counter-offense, with molecular memory capable of neutralizing future viral attacks.

Covid-19, SARS and MERS are acute, rapidly progressing, pan-inflammatory infections that, predicated upon the coronavirus quasispecies involved, may present distressful morbidity and mortality outcomes. A salient clinical configuration in these infections stems from their acute involvement of the respiratory system, and their rapid disruption of blood gas balance. When pO2 and pCO2 are sufficiently compromised, chemoreceptors in the medulla begin to fail and respiration stops.

Because of their galloping symptomatology, Covid-19, MERS and SARS ideally would benefit from proactive emergency viral culling. With estimated 10 billion viral particles disgorged daily in the general circulation, viremic reproductive juggernauts commonly seen in lipid-enveloped viral cycles need modulation.

Can systemically administered oxygen/ozone mixtures assist in this process? In severe Covid-19 cases, the disease progression may be stunningly rapid. Present countermeasures are non-existent. Indeed, Covid-19 may need more intensive intervention and emergency abatement of viral aggressiveness.

COVID-19, MERS and SARS: disinfection/sterilization of the environment

The recent findings that Covid-19 has the capacity to remain infectious on fomites for up to several days indicates that it is a hardier organism than most of its other lipid-enveloped colleagues.

Predictably, disinfectants such as bleach, phenol, formaldehyde and ozone have been found to be effective in deactivating the coronaviruses. Liquid agents have the disadvantage of faring poorly in decontaminating complex medical equipment and the hospital room milieus of coronavirus patients. Medizone International Inc., has developed a patented ozone/hydrogen peroxide mix that is remarkably effective in decontaminating the surfaces, nooks and crannies of hospital treatment rooms and patient rooms (and ships’ quarters), from all pathogenic organisms.

Ozone, in light of its pan-virucidal profile, offers the advantage of existing as a gas, with its attendant ability to disinfect poorly accessible spaces. Moreover, ozone has the distinct benefit of naturally reverting to natural oxygen molecules, while liquid–based disinfectants are likely to injure the surfaces to which they are applied, and to leave toxic residues. Ozone-mediated environmental decontamination, however, needs to respect stringent protocols to insure that the ambient ozone in the process of disinfecting target environments has time to revert to its stable parent, oxygen, without inflicting toxicity to the personnel.

Summary and conclusions

Covid-19, SARS and MERS are acute pan-inflammatory multi-system syndromes caused by hitherto unknown coronavirus species. These virions incorporate novel RNA genomes and lipid bilayered envelopes. The Covid-19, SARS and MERS viruses all possess high mutation rates, allowing any one infected individual to harbor numerous quasispecies, all with variable infectivity and lethality.

Ozone is an energy-rich naturally-occuring molecule that embodies unique physico-chemical and biological properties suggesting a possible role in the systemic therapy of Covid-19, MERS and SARS, either as a monotherapy or, more realistically, as an adjunct to standard treatment regimens. Ubiquitously found in the earth’s ecosphere, ozone, amazingly, is also intrinsically found in bodily systems, generated by normal immune functions as an inactivator for multitudes of pathogens.

This paper outlines six possible mechanisms by which ozone may exert its antiviral actions. Due to the excess energy inherent in the ozone molecule and supported by the vast scientific literature attesting to its pan-microbial powers, it is quasi-certain that ozone can demonstrate effectiveness across the entire coronavirus spectrum.

The acute infective phase of Covid-19 is marked by massive viral replications, with viral flooding of blood and lymph compartments. These viremic invasions present serious clinical challenges because they contribute to the swiftness of downhill clinical courses. This paper proposes a method of viral culling, during these acute phases of coranovirus illnesses, via systemically administered oxygen/ozone gas-to-blood interfacing strategies.

Herewith proposed is consideration for the modification of technologies that already use blood-to-oxygen interfacing for assisting patients in cardiopulmonary distress for maintaining proper blood gas configurations. The technology, developed since the 50’s, and known as extracorporeal membrane oxygenation (ECMO), can be upgraded to accept ozone’s addition by rendering its systems, such as gas exchange membranes, ozone-resistant. Posited is that appropriately calibrated added ozone dosages can become adjuncts to the mission of assisting Covid-19 patients maintain not only healthy blood oxygen/carbon dioxide balance, but also provide them with Covid-19 viral harvesting and elimination.

Ozone has unique disinfectant properties. As a gas, it has a penetration capacity that liquids do not possess. In view of the fact that Covid-19, MERS and SARS persist on fomites for up to several days, it is suggested that ozone technology be applied to the decontamination of medical and other environments.

As our world becomes increasingly challenged by viral adversaries, the need for rapidly developing specific vaccines adapted to each viral species becomes evident. Yet, in parallel, research also needs to center on finding new methods of relieving the biological stress caused by onslaughts of viremic invasions that are common to many families of pathogenic viruses. The coronaviruses are a case in point, as they all possess lipid envelopes susceptible to structural modifications by ozone.

In conclusion, a proposal is herewith made that oxygen/ozone systemic therapies are granted research consideration for Covid-19 treatment. Such therapeutic approaches may then be found useful not only in these specific coronavirus conditions, but also in a number of human lipid-enveloped viral pathogenic infections, and importantly for the future coronavirus epidemics that are certain to emerge.

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