SARS-CoV-1 and MERS are familiar terms to me because I happened to be in China when these broke out. I never wonder why Chinese tourists wear masks wherever they go. People from China have come to hate viruses, and want to protect themselves whenever and wherever they go. When SARS-CoV-2 became a pandemic in early 2020, I was head of the supervisory board of a live entertainment company, and knew our artists would not see a stage for the next years to come. That was not acceptable – so I started calling my engineering friends around the world. The best was my friend in civil engineering from the Punjab. Punjabi people can make ends meet with very little.
We took to the blackboard to discuss the requirements for a technical answer to infections in buildings: (i) it has to be natural, as anything chemical would not be acceptable, (ii) it has to be cheap, as it is a pandemic, and we need to take care of the poorest amongst us, and (iii) it has to be thorough, as just marginal betterments would not be good enough. Filtering does not comply with (ii) and (iii), so we would have to introduce an agent into the air, and any other substance apart from HOCl (hypochlorous acid) does not comply with (i); thus HOCl it was.
One stepping stone after another
Now needing to isolate the molecule, bring it into the air, and to be able to measure it, we went to the laboratory. Nature itself provided one stepping stone after the other. HOCl is natural, it can exist as a molecule in the air, it decays automatically but not too fast, and – most importantly – it is not harmful for mammals to inhale, even over extremely long, uninterrupted periods. Producing HOCl outside a mammal’s body is inexpensive, as it takes only water and salt. oji active air can eliminate all bacteria and viruses from both the air, and all surfaces, in a matter of minutes. For spores and yeast it takes a bit longer – but then it is continuous, and in the background, so that people get back their freedom – without masks and social distancing.
Historical use HOCl
The first variant of hypochlorous acid – called ‘Eau de Javel’ – was produced over 200 years ago by Percy and Berthollet in the French village of Javel in the form of potassium hypochlorite (KOCl). A short time afterwards, but before Pasteur discovered that living organisms can cause infectious diseases, Labarraque and Semmelweis found that HOCl was very effective in preventing wound infections and the transmission of puerperal fever. Its anti-infectious properties were recognised even before the widespread use of aqueous chlorine as an antiseptic for traumatic illnesses.
During World War I, the use of HOCl was developed for general hygiene, for wounds, and for therapeutic applications in gangrene, diphtheria, and scarlet fever.
Aqueous chlorine has been the antiseptic of choice for several decades. However, the preparation of the solutions, which should be high in HOCl, was difficult, and the results varied widely.
Rapid degradation
The instability of many of the solutions produced resulted in rapid degradation over hours, and produced several problematic chlorine species, including molecular chlorine (Cl2), chlorate (ClO3 – ), hypochlorite (ClO– ), and other molecules that were toxic to tissues and corrosive to surfaces. When solutions mainly consisted of HOCl, they were most effective, and had the highest disinfecting power.
In the 1940s, aerosolised solutions of acidified hypochlorite were used in London hospitals as a control measure against airborne pathogens. At that time there was already a clear understanding of the contribution of the HOCl to the observed result, and not of the chlorite ion (OCl– ), which is partially in solution. Decades later came the discovery that HOCl is also naturally formed in activated human neutrophils and other tissue-own phagocytes.
HOCl in the body
HOCl is both a key player as part of the innate immune response system, and a powerful adjunct augmenting physiological responses. The study of external exposure and delivery of HOCl has recently seen a renaissance as a research field. The development of products to both simulate and augment the physiological HOCl functions has gained enormous interest. In particular, the extracellular attack of pathogens prior to their intracellular replication has become an active area.
All practical pathways of administering HOCl have been investigated, and demonstrated as a safe and effective way to boost the innate immune response. The methods span nasal and pharyngeal inhalation, topical applications (e.g. wound care), intraoperative (e.g. peritoneal lavage), gastrointestinal, ocular, and even systemic intravenous (IV) delivery.
Protecting the epithelia
Externally applied HOCl can play an important role in the protection of respiratory system epithelia against viral infections. The importance of a parallel occurring intracellular innate immune response effect has also been demonstrated: inhibition of coronavirus infection within cultured epithelial cell lines with externally applied HOCl coincide with intracellular production of HOCl. Apparently, administered HOCl can foster and complement the intracellular HOCl response with direct extracellular pathogen attacks, or by stimulating the intracellular HOCl production rate.
The interrelationship of HOCl-connected extra- and intracellular effects was shown with the markedly inhibited rhinovirus replication in primary cultured nasal epithelial cells by the exposure of infected cultures to HOCl, suggesting that exogenous sources of HOCl may be able to intervene in the maturation of intracellular virions. Externally applied HOCl plays an important role in stimulating a part of the innate immune system known as mucosal immunity. That is a first line of defence concentrated in cells lining the respiratory tract, and other surfaces like the intestines and the urogenital tract, which doesn’t tend to be activated by conventional vaccines.
Saline solution – promoter of HOCl production
A recent scientific discovery demonstrates a natural, safe, and accessible selfadministered procedure that enhances our innate immunity. Non-myeloid epithelial cells can produce HOCl. The amount of HOCl generated is dependent on the concentration of available intracellular chloride. In vitro, saline exposure of epithelial cells infected with coronavirus significantly reduced viral replication. In vivo, hypertonic saline nasal irrigation and gargle (HSNIG) in patients who had upper respiratory infections (URI) caused by coronavirus significantly reduced the duration and severity of the URI compared to similarly infected patients treated with the standard care. HSNIG can suppress viral replication of COVID-19, mitigating the spread during the asymptomatic phase, and reducing the risk of an asymptomatic or symptomatic case progressing to a severe infection.
Enhanced quality of life
Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl– ) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. This suggests that nonmyeloid cells possess an innate antiviral mechanism – dependent on the availability of Cl– to produce HOCl. Thus, antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.
Many studies evaluating the efficacy of saline irrigation have indicated a clear improvement in the quality of life of patients undergoing treatment for various diseases, including rhinosinusitis and allergic rhinitis, and in the postoperative care of patients who have undergone endoscopic sinus surgery. However, saline irrigation may be less effective than use of HOCl-activated solutions for uncontrolled rhinosinusitis, because saline irrigation by itself lacks an antibacterial effect, and mucin is hydrophobic.
Inhaling approach
In addition to nasal irrigation with hypertonic saline solutions, the inhaling approach has been studied extensively. The most important practical advantages of this method are its simplicity, and very low probability of adverse events, as observed in a meta-analysis study where safety data was reviewed in 24 trials: 13 trials (1,363 neonates, 703 treated with hypertonic saline) reported no adverse event, and 11 (2,360 infants, 1,265 treated with hypertonic saline) reported at least one adverse event, most of which were mild and resolved spontaneously
For more than the last decade HOCl has played an increasingly important role in wound care. For antisepsis and wound decontamination, HOCl solutions are applied topically. Applications are often repeated during the day in the early stages of wound management, and are adjunctive to debridement and other procedures aimed at adherent soil and biofilm removal. HOCl-soaked wound dressings are relied upon for continued delivery of antimicrobial and healing enhancement benefits over time.
Hypochlorous acid exhibits antiinflammatory and immunomodulatory properties based on multiple laboratory analyses. These properties appear to correlate with potential therapeutic benefits of topically applied HOCl for a variety of skin disorders. There exist numerous examples of how the use of HOCl has outperformed many conventional (e.g. antibiotic) treatment schemes in both its efficiency and long-term patient acceptance. For example, Bongiovanni et al provided a comprehensive review of use of HOCl in the treatment of more than 1,000 venous leg ulcers (VLU). His summary speaks for itself: “Perhaps the greatest advance in VLU care is the addition of HCA [hypochlorous acid, HOCl] to the treatment armamentarium. These aqueous solutions of hypochlorous acid, even in trace amounts, will kill most pathogens within 30 seconds of exposure. Additional actions of HCA include reduction of mast cell degranulation, and active capillary dilation.
“The latter effect is of great importance in the diabetic VLU patient, since one of the paradoxes in diabetes is the reduction of capillary perfusion via arteriovenous shunting at the microcirculatory level.”
The ‘ideal disinfectant’
Block and Rowan in 2020 reviewed surgeons’ needs for disinfection in the face of the coronavirus pandemic, and concluded that ‘HOCl comprises many of the desired effects of the ideal disinfectant: it is easy to use, is inexpensive, has a good safety profile, and can be used to disinfect large areas quickly and with a broad range of bactericidal and virucidal effects’.
There are no reports of adverse reactions to topical applications by these methods based on the US EPA’s Toxicology Database DSSTox, or the US CDC Toxic Substances and Disease Registry, nor at either the Development and Reproductive Toxicology Database, or the European Bioinformatics Institute of EMBL.
oji active air – what is it, and why is it good?
oji active air changes the indoor climate from potentially dangerous – with pathogens in the air and on surfaces – to a safer one, by maintaining a certain concentration of HOCl molecules in the building’s air. The air, and all surfaces exposed to it, are maintained free from pathogens. People cannot get infected in this building any more
Indoors, pathogen-carrying aerosol particles are recognised as important infection carriers like those in the current coronavirus pandemic. This infection route is often underestimated, yet represents the infection route that has been least systematically countered to date. Current indoor safety measures (e.g., distancing, masks, filters) provide only limited protection. Inhalation of hypochlorous acid (HOCl)-containing aerosols was recently shown in several studies to be safe and effective in prevention, and even in reduction of symptoms, of already infected individuals.
A controlled environment
For our tests, we aerosolised bacterial suspensions into a controlled office space. The HOCl concentration was held at constant concentration with a softwarecontrolled injection system (aerosolis device; oji Europe GmbH, Nauen, Germany) and a special HOCl gas sensor unit (Dräger AG, Lübeck, Germany). We confirmed the disinfecting power of the used HOCl in suspensions, and demonstrated the high efficacy of vaporized HOCl to deactivate airborne pathogens at safe and non-irritant levels (Microbiology Lab of Henkel, Düsseldorf, Germany).
Incorporating this air disinfection technology into building ventilation systems could make a valuable contribution to future infection prevention and control. It may take facility management to a new level of providing environmental safety
What is the technology?
oji active air is a system that produces HOCl in situ (i.e. at the customer location) from water and salt. Subsequently, the HOCl molecules are separated from any remaining other minerals and water, and fed into the building’s ventilation system. Within the HVAC system’s return air duct a sensor monitors the HOCl concentration in the air. oji active air is a fully automated system that always maintains a healthy concentration of HOCl molecules in the building; it is a ‘dry’ disinfection method
In contrast, ‘classic’ nebulisation is a ‘wet’ process. Aqueous solutions of disinfectants spray water droplets with high intensity and large volumes into the room atmosphere. The droplet diameter varies from around 300-1,000 µm. Such large droplets cannot hover for long in the atmosphere, and sink into and cover all surfaces. This includes penetrating electronic hardware – either through passive vent openings, or active suction caused by device ventilators. Nebulisation of mineralised water or aqueous disinfectant solutions have thus been identified as a hazard to electronics, including medical devices in hospitals and private homes
Dry aerosolisation of aqueous solutions produces extremely small droplet sizes, and the droplets created will not the sink into and wet surfaces. The disinfecting effect of surfaces is due to the gas-based (diffusion-based) nature of the distributed disinfectant. Therefore, aerosolised aqueous HOCl solutions do not present a hazard for indoor surfaces or electronics, or indeed HVAC systems. oji active air technology can be installed on any type or size of ventilation system in a matter of a day, and at very low cost. The aerosolised product does not leave any residue on surfaces, or react with surfaces in the building. The HOCl concentration is extremely small – in fact just sufficient to eliminate viruses and bacteria within seconds
What are the benefits for the hospital?
Proactive facility management harnessing novel ventilation concepts can become an important contributor to future infection prevention and control. The importance of our results is two-fold:
Infection prevention: HOCl-laden air may offer a safe, low-cost, and efficient way to secure an effectively pathogen-free atmosphere. In facilities using the technology the threat posed by infected people spreading the virus among individuals would be contained effectively. As part of the hospital’s hygiene and infection prevention and control strategy, oji active air would reduce the need for manual, sporadic surface disinfection, and help minimise any ‘downtime’ resulting from implementing other disinfection methodologies.
Slowing disease progression: HOCl-enriched air has the potential to contain or even invert the progress of disease by attacking mucosa-adsorbed viruses during the incubation phase. As a result, the ventilated and HOCl-treated atmosphere within the healthcare facility could offer a seamless disease containment function, speeding patient healing, and in some cases even obviating the need for the use of antibiotics.
Today, any microbial ingress will only be partly contained with incumbent safety measures. We have confirmed our theory about the powerful disinfecting ability of HOCl-laden air, while a number of peerreviewed studies (e.g. Rai, Ashok, and Akondi 2020; Lapenna and Cuccurullo. 1996; Mohapatra and Wexler. 2009) have demonstrated that the technology is safe to use in populated indoor environments at the investigated concentration levels.
Wide-ranging applications
The potential of HOCl-laden atmospheres to convert populated indoor areas into infection-protected environments points way beyond COVID-related applications. Our reported results and ongoing laboratory and field tests in large office buildings suggest the use of HOCl-based room air decontamination counters the need for high air exchange rates for infection control – potentially affording the opportunity for significant energy savings. The HOCl air cleaning technology is safe, cost-effective, and easy to install and maintain.
Other applications in healthcare
The importance of disinfection using HOCl is increasing, particularly due to the appearance of increasingly resistant microbes, from flaviviruses to highly invasive forms of everyday Candida yeasts. Environmental hygiene, disinfection, and food safety/hygiene will hopefully benefit indirectly from the increased research
The microbes investigated in our trials (Gram-positive, Gram-negative bacteria, and Vaccinia virus) can be understood as a general model for infectious particles, including enveloped viruses (to which Coronavirus belongs). Those using aerosolised aqueous HOCl solutions with a droplet diameter of under 10 µm should see no corrosive or negative effect on surfaces or electronics, meaning the results we have seen make the technology directly applicable as a real-world indoor air disinfection solution. These early results suggest that HOCl based in-air cleaning should be further evaluated. Due to the broad operating window of HOCl between effective and safe concentration levels, it may present a valuable addition to existing infection control processes such as ventilation, air filter systems, and personal hygiene protection.
Dr Thomas Bone-Winkel
Dr Thomas Bone-Winkel is an experienced and international manager. In 2020, he founded oji with his partner, Gundeep Singh, in Dubai. oji produces electronic lock systems (oji smart, GCC) and continuous disinfection systems (oji life, Europe). He served as MD of a Chinese investment group from 2016-2020, while between 2013 and 2016, he was CFO of German live entertainment company, Apassionata. He has a solid banking background, acquired in the private equity and structured finance business of ABN AMRO Bank. As head of the Bank’s German Structure Finance activities, he was responsible for private equity, cross-border tax-driven financing structures, and structured debt/equity transactions in Europe, the Americas, and Asia. He also has an accounting background acquired at Peat Marwick (today KPMG), having specialised in international tax and financing from 1992 through 1997. A Certified Public Accountant (United States), he holds a Master’s degree in taxation from Cologne University, and a Doctor’s degree in international tax from Göttingen University.