Statement on the use of Nemesis eH2O in fighting COVID-19
Around the world, countries are seeking effective ways to prevent the spread of the coronavirus pandemic, and the disinfection of surfaces (including skin) is one of the most important measures that can be undertaken. However, when choosing a disinfectant or hand sanitiser, it is important to check that it is fit for purpose. (See separate article on the importance of reading the label)

Background
The word COVID-19 represents Corona (CO) Virus (VI) Disease (D) and 19(2019) is the year that the first cases were detected – in China’s Wuhan City, which was eventually locked down on 23rd January 2020. Wuhan had 11 million inhabitants, but tens of millions of citizens in nearby cities were also locked down.

Italy was locked down on 9th March, and on 17th March the European Council agreed to ban incoming travel. On 25th March India placed its 1.3 Billion population on lockdown until at least 3rd May. In the USA, three out of four Americans were placed under some form of lockdown, and by the end of March around one third of the global population was on Coronavirus lockdown.

Coronaviruses belong to one of two subfamilies: Coronavirinae and Torovirinae. They are enveloped viruses, first isolated in the 1960s from the nasal cavities of patients suffering with colds. Coronaviruses are believed to be responsible for 10-15% of colds worldwide and have a seasonal pattern. They primarily affect the upper respiratory tract of mammals and birds, and cause direct (viral) and secondary (bacterial) pneumonia and bronchitis.

Coronaviruses – enveloped viruses
The outer coating or viral envelope is composed of a lipid layer which is needed in the attachment of the virus to a host cell. Loss of this envelope causes loss of infectivity.

Enveloped viruses are easily inactivated by routine surface cleaning and disinfection. For example; treatments with ultraviolet (UV) radiation or Nemesis eH2O hypochlorous acid usually destroy the viral genome, whereas chlorine dioxide and heat interrupt the process of host cell recognition for virus binding (Wigginton, 2012).

Table 1: The seven strains of Coronavirus known to affect humans

Variant Genus Year first reported
Human CoV 229E AlphaCoronavirus
Human CoV OC43 BetaCoronavirus
SARS-CoV BetaCoronavirus 2003
Human CoV NL63 AlphaCoronavirus 2004
Human CoV HKU1 BetaCoronavirus 2005
MERS-CoV BetaCoronavirus 2012
2019-nCoV (COVID-19) BetaCoronavirus 2019

Coronaviruses cause a wide range of disease in farm animals and domestic pets: porcine CoV, bovine CoV (both cause diarrhoea in young animals), avian CoV (respiratory tract), Canine CoV (two types), Feline CoV (two types, both associated with high mortality rates), ferret CoV (two types) and murine CoV (high mortality rate). Coronaviruses are also present in wild animal species e.g. bats, camels and snakes. Some of these have effective vaccinations but they are zoonotic and freely mutate, so new viral pandemics continue to pose a significant threat to humans and animals.

Emerging viruses
The term ‘emerging virus’ describes those which have increased over the past twenty years, or whose presence threatens to increase in the future (Artika and Ma’roef, 2017). This includes those that have been newly diagnosed or those that may have been present before, but have mutated. Viruses that meet this definition include the highly pathogenic avian influenza (HPAI) virus of subtype H5N1, SARS-CoV, Ebola, MERS-CoV, Zika and most recently the new variant SARS‑CoV‑2.

The majority of emerging viruses are zoonotic – diseases that normally exist in animals but that can infect humans. Their appearance is believed to be driven by a number of factors such as socio-economic, environmental and ecological changes (Jones et al., 2008). The world’s population increased from 1 billion in 1800, to 7.7 billion in 2019. At the same time, there have been dramatic increases in global trade and travel. These factors have contributed to the increased chance of the emergence and re-emergence of viral diseases. Prior to the COVID-19 pandemic, two strains have been associated with serious outbreaks. These were SARS and MERS.

According to the World Health Organisation (WHO) the severe acute respiratory syndrome coronavirus (SARS-CoV) affected 26 countries and caused more than 8,000 cases in 2003. Transmission of SARS is primarily from person to person, and cases of human-to-human transmission occurred in healthcare in the absence of adequate infection control. Implementation of infection control practices brought the global outbreak to an end.

Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012. The mortality rate for people with the MERS virus is approximately 35% although this may be an overestimate because mild cases may be missed by existing surveillance systems.

History lesson
In 1841 a Hungarian obstetrician Dr Semmelweis, working in a Vienna hospital, was shocked by the number of women dying from puerperal fever. He observed that mortality rates were three times higher in the ward where medical students were delivering babies in comparison with an adjacent ward, staffed by midwifery students. The medical students were also working with dead bodies, so he suggested that the medical students may be infecting the women. He therefore implemented mandatory hand-washing in May 1847 – and infection rates dropped dramatically. Thereafter, the connection between microorganisms and disease transmission was established and the requirement for disinfection and decontamination became better understood.

Environmental persistence
The persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents has been reported by Kampf, G. et al. (2020), and a brief summary is given on the Nemesis eH2O product page.
SARS has been shown to persist on hard surfaces for up to 96 hours (Duan et al., 2003) and up to 5 days if dry (Rabenau et al., 2005b); MERS persists for at least 48 hours on surfaces (Hui et al., 2018). Research has shown low concentrations of MERS RNA in environmental swabs taken from bed guardrails and monitors. Even after cleaning the monitors with 70% alcohol based disinfectant, low concentrations of MERS RNA remained, and the samples only became negative for MERS after the monitors were wiped with diluted sodium hypochlorite (Song et al., 2015). This is consistent with the findings of other researchers such as Rabenau et al. (2005) who found that alcohol gels were effective against feline calicivirus in the presence of fetal calf serum, but not effective in the presence of sheep erythrocytes or serum albumin. In summary, it is clear that alcohol gels should not be considered efficacious under all ‘dirty’ conditions.

Decontamination
The word decontamination means the removal of dangerous materials such as hazardous substances and infectious diseases from equipment and environments. Decontamination can be a combination of processes, including cleaning, disinfection and sterilisation, but the effectiveness of decontamination can only be determined when there is a defined objective.

Logarithmic reduction is the standard used for quantifying disinfection. For example, healthcare disinfection may require a ≥6-log reduction of test organisms, Staphylococcus aureus, and Pseudomonas aeruginosa in ≤10 minutes. So, a 1-log reduction in colony forming units (CFUs) represents a 90% reduction and 2-log represents a 99% reduction. 6-log reduction therefore represents a reduction of CFUs by 99.9999%. To put this in perspective, a typical supermarket sanitiser with 99.9% efficacy (3-log) could be expected (in the right conditions) to reduce a colony of 1 million CFUs to 1,000 CFUs whereas a 6-log sanitiser (such as Nemesis eH2O) would reduce the same size colony down to just one CFU.

Disinfectants destroy micro-organisms and the aim of disinfection is to reduce the numbers of viable micro-organisms to a level that is not harmful to health. Antiseptics are substances that can be applied to skin or tissue in order to reduce the possibility of infection.

Disinfecting surfaces
Inanimate surfaces can represent a significant source of infection, so the correct use of disinfectants is extremely important. Rabenau et al., 2005 found that SARS can be inactivated (4-log reduction) quite easily with many commonly used disinfectants with a 30 – 60 minute contact time. Dellano et al. (2009) tested a range of household disinfectants including sodium hypochlorite, against Murine Hepatitis Virus (a SARS surrogate). They found that a 30 second contact time was sufficient to achieve a 4.5-log reduction of MHV dried onto stainless steel coupons.

Nemesis eH2O hypochlorous acid is safe for humans and the environment. Clark et al., 2006 demonstrated excellent performance with up to 7-log against MRSA (on ceramic tiles). Informal studies have repeatedly demonstrated that Nemesis eH2O products are effective against bacteria and viruses in a wide range of applications including food safety, animal production and health care.

One of the most commonly studied viruses is Feline calicivirus (FCV) because it is relatively easy and safe to work, and can be used as a surrogate for norovirus. Both norovirus and FCV are non-enveloped viruses which are harder to kill than enveloped viruses such as Coronaviruses. Many studies have assessed the inactivation of FCV with acids and alcohols (Whitehead and McCue, 2010), ozone gas (Hudson et al., 2007), hydrogen peroxide vapours, and chlorine dioxide gas (Morino et al., 2009). Whitehead and McCue (2010) showed that bleach and acid-based disinfectants could inactivate FCV within 1 min (>4-log reduction). Some of these compounds are toxic, some are expensive or difficult to apply, and most require an extended time for virus inactivation. Nemesis eH2O hypochlorous acid (150ppm) achieved >5-log reduction in FCV titres in less than a minute (Chander et al., 2012).

Fogging and spraying
Whilst fogging, spraying, or aerosolisation provide an efficient mechanism for the delivery of a liquid disinfectant, the material safety data sheets and labels for many virucidal compounds rarely permit these application methods, due to their toxicity and adverse health effects. Several of these chemicals, such as sodium hypochlorite, chlorine gas, and glutaraldehyde, have been associated with occupational illnesses. For example, exposure to glutaraldehyde is associated with contact dermatitis, and the use of quaternary ammonium compounds can cause occupational asthma (Purohit et al., 2000; Ravis et al., 2003). Where aerosolisation is approved, the use of personal protective equipment (PPE) and a self-contained breathing apparatus is usually required, which makes the use of these compounds difficult, especially in public places such as hospitals or schools.

Fogging has also been tested as a virucidal vehicle for disinfectants: Knotzer et al (2015) fogged stainless steel coupons with dry residue of both enveloped and non-enveloped viruses. 5 minutes fogging with hydrogen peroxide / peracetic acid was sufficient to achieve inactivation. However, hydrogen peroxide is toxic to humans and inhalation causes irritation to the respiratory tract. In very severe cases bronchitis or pulmonary oedema may occur, which can be fatal. Contact with the skin causes bleaching and possibly permanent scarring. Consequently, in addition to a wide range of safety precautions, rooms being treated with hydrogen peroxide vapour must be evacuated and sealed.

Nemesis eH2O hypochlorous acid has been demonstrated as a powerful disinfectant and has been shown to be efficacious against a wide range of microorganisms in solution and when sprayed in the air. Another significant benefit of Nemesis eH2O hypochlorous acid is its lack of toxicity at ready-to-use (RTU) concentrations. Informal testing has repeatedly shown that fogging of Nemesis eH2O RTU hypochlorous acid products achieves safe and consistent log reductions in bacterial and viral loading, both on environmental surfaces and food products.

The SARS and MERS outbreaks were emerging diseases so no medical treatment or vaccines were available and control of the epidemics relied on rapid diagnosis, isolation of patients and attention to infection control. This remains the case for any future pandemics caused by emerging viruses such as COVID-19. According to WHO (2015) cleaning surfaces with water and detergent followed by the application of a commonly used disinfectant is an effective and sufficient procedure to ensure good environment hygiene.

Rutala and Weber (2014) proposed a hierarchy approach to anticipating effectiveness, based on resistance to disinfection – see Table 2.

Table 2: Hierarchy of Microbial Resistance to Disinfectants and Sterlilants

Microorganism Aqualution (Nemesis eH2O) BS EN tests
Most Resistant Spores (eg C. difficile) BS EN 13704:2002; BS EN 13727:2003
Mycobacteria (eg M. tuberculosis) BS EN 14204:2012; BS EN 14348:2005
Non-Enveloped Viruses (eg norovirus, polio) BS EN 14476:2013
Fungi (eg Candida albicans) BS EN 13697:2001; BS EN 1275:1997
Bacteria (eg MRSA, VRE, Acinetobacter) BS EN 1040:2005; BS EN 1276:2009; BS EN 13697:2001; BS EN 1656:2009
Most Susceptible Enveloped Viruses (eg HIV, influenza) BS EN 14476:2013
Adapted from Spaulding, 1957 and Rutala and Weber, 2014

The most susceptible microorganisms, enveloped viruses, are at the bottom of Table 2. SARS‑CoV‑2 is an enveloped virus so it is reasonable to expect disinfectants that are effective against other enveloped viruses to also be effective against this Coronavirus, when used as per the directions of use. It is not yet possible to test Nemesis eH2O products against SARS‑CoV‑2 because the strain is not available for laboratory testing. In addition, even when samples are available, it will not be possible to make any definitive claims until regulators review and approve those claims. Nevertheless, Nemesis eH2O products have passed internationally accepted Standards tests for virus efficacy, in addition to in-house testing against a wide range of viruses, both enveloped and non-enveloped.

Nemesis eH2O has passed all the BS EN tests highlighted in Table 2. Tests have also been conducted on a wide range of other organisms to satisfy the very vigorous demands of the Biocidal Products Regulation (BPR) under which the Nemesis eH2O active substance is approved.

Rutala and Weber, 2014, suggested that there are 5 key considerations when selecting a disinfectant in a health care situation:

  1. does the product have sufficient efficacy against relevant pathogens?
  2. how fast are the pathogens killed, and do surfaces remain visibly wet for the kill times listed on its label?
  3. is the product safe for use in terms of toxicity and flammability? Is PPE required and is the product appropriate for all target surfaces?
  4. is it easy to use – is the shelf life acceptable and are the directions for use clear and simple?
  5. is training and support available? And is the cost acceptable?

Nemesis eH2O scores very highly in assessments such as that outlined above. Combined with effective procedures and appropriate training, Nemesis eH2O helps deliver effective surface disinfection; reducing infection risk and improving outcomes in domestic, community and healthcare settings.

Comparing Nemesis eH2O with alcohol-based sanitisers
Most alcohol-based hand antiseptics contain ethanol, isopropanol or n-propanol, or a combination thereof. According to the WHO, the main advantages of alcohol-based hand sanitisers are that they are fast-acting and broad-spectrum. In a healthcare setting they can overcome the limited availability of taps/basins and lower costs.

Alcohol solutions containing 60–80% alcohol are most effective, with higher concentrations being less potent. Alcohols have excellent in vitro germicidal activity against Gram-positive and Gram-negative vegetative bacteria and a variety of fungi. However, they have virtually no activity against bacterial spores or protozoan oocysts, and very poor activity against some non-enveloped (non-lipophilic) viruses.

Frequent use of alcohol-based formulations for hand antisepsis tends to cause drying of the skin unless humectants or other skin conditioning agents are added to the formulations. However, even well-tolerated alcohol-based handrubs containing humectants may cause a transient stinging sensation at the site of any broken skin.

Alcohols are also highly flammable so appropriate safety precautions are necessary if the product is used near sparks or open flames.

Nemesis eH2O hypochlorous acid achieves >5-log viral reductions in less than a minute and is therefore effective in a spray and wipe cleaning regime. It is safe for people and the environment, and can be misted around people and animals with no deleterious effects and no toxic residues. Workers do not need any PPE to handle Nemesis eH2O and it can be used on soft and hard surfaces. It is extremely versatile and can be used simply as a dip, spray, mist or fog, so compliance is high. It does not lose efficacy at low temperatures, and has a 12 month shelf-life if kept in suitable storage conditions.

CONCLUSIONS
SARS-CoV, MERS-CoV and 2019-nCoV are emerging diseases with no immediate availability of medical treatment or vaccines. This will also be the case for future zoonotic viral pandemics. Evidence indicates that viruses, especially enveloped, are relatively easy to inactivate and a wide range of disinfectants may be effective.
Rapid case identification, isolation and infection control measures are essential to prevent the spread of these emerging viral diseases within households, communities and health care facilities. Nemesis eH2O hypochlorous acid is not specifically tested against 2019-nCoV – no disinfectant is – but it is tested and efficacious against a wide range of microorganisms including spores, bacteria and other viruses (enveloped and non-enveloped) leading to the reasonable conclusion that it will be effective against COVID-19.

Viruses are able to persist in the environment for days but are relatively easy to kill. Disinfectants should therefore offer complete virucidal activity against both enveloped and non-enveloped viruses.

Nemesis eH2O hypochlorous acid has been tested against viruses and has been shown to have virucidal properties (Pineau, 2000). It has achieved >5-log reductions against orthopoxvirus (enveloped), adenovirus (non-enveloped) and poliovirus (non-enveloped).

Disinfectants work best in clean conditions so it is important to clean (with a detergent) and to then disinfect for optimal results. Whilst some products pass laboratory virucidal tests, they do not work well in real-world conditions, especially in the presence of soil/organic material. Furthermore, many products are effective in lab tests but need extended contact times (30 minutes to several hours) to be effective. Again, this is not compatible with the real-world requirements for an effective disinfectant. In contrast, Nemesis eH2O hypochlorous acid is fast acting with contact times typically less than a minute. It is versatile and can be used as a dip, skin irrigant, spray, mist or fog.

Nemesis eH2O is extremely effective against a wide range of micro-organisms, including enveloped viruses. As such it is suitable for use as a broad spectrum, easy to use, efficacious and safe disinfectant.

REFERENCES
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Chander, Y., Johnson, T., Goyal, S.M. and Russell, R.J. 2012. Antiviral activity of Ecasol against feline calicivirus, a surrogate of human norovirus. Journal of Infection and Public Health. 5 (6): 420-424.

Cho, S.Y., Kang, J.-M. and Ha, Y.E. 2016. MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study. Lancet. 388: 994–1001.

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