Soap, water, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an ancient handwashing strategy for preventing dissemination of a novel virus

Introduction

Personal hand hygiene, and hygiene in general, have played an integral role in several religious and cultural norms within different societies for centuries. Hand washing with soap is routinely employed as part of personal hygiene during everyday life in developed countries (World Health Organization, 2009). However, the important role played by contaminated hands in dissemination of infectious agents has only been realized since the 19^th century (Semmelweis, 1861).

The interventional role of hygiene agents in disrupting the chain of infection of pathogens is now well established (World Health Organization, 2009; Alum, Rubino & Ijaz, 2010; Stephens et al., 2019; Scott et al., 2020; Scott, Bruning & Ijaz, 2021). Many infectious agents, including both respiratory and enteric viruses, as well as a variety of non-viral pathogens, are spread by contaminated hands (World Health Organization, 2009). Hand washing with soap and water has been recommended as one of the most important measures for prevention of dissemination of the spread of viruses, including SARS-CoV-2 (United States Centers for Disease Control & Prevention, 2020a). In healthcare settings, non-compliance with hygiene practices predisposes healthcare workers to the dissemination of nosocomial infections. This is an important lesson, well known in the infection prevention and control community, but perhaps only more recently by the public-at-large. During a pandemic associated with an extremely contagious respiratory (and possibly enteric) virus, such as SARS-CoV-2, the routes of infection spread can be visualized as a cycle from infected persons to non-infected persons directly through contaminated droplets suspended in the air and/or contaminated high-touch environmental surfaces (HITES) and hands directly or indirectly (Fig. 1).

Survey methodology

This traditional review of the literature was intended to address, at a high level, a number of topics germane to the efficacy of soap and water hand washing as an intervention for limiting the person-to-person spread of SARS-CoV-2. As such, our methods for ascertaining relevant literature were not intended to allow access to all of the literature. In fact, we did not use, at the onset, exclusion criteria for accessing the literature. We simply searched the relevant literature in Google Scholar and PubMed on each of the topics covered in the review (see abstract and the subject headings below). Search topics used therefore included SARS-CoV-2 and coronaviruses; transmission routes; persistence (stability) on surfaces, skin (hands), and human excreta; general relevance to infection prevention and control of hand hygiene and hand hygiene practices; mechanism of action of soap and water washing for reducing contamination of hands; soap formulation components and their functions and potential contributions to pathogen inactivation; the role of antibacterial soaps and potential antimicrobial components in hand soaps; efficacy of hand soap products specifically for inactivating SARS-CoV-2; the concept of contact time and decimal reduction value as this informs duration of hand washing; the role of water temperature in hand washing as an intervention for limiting spread of SARS-CoV-2; the role of hand drying options and preferability of disposable hand towels during an infection outbreak; hand washing with soap and water vs. use of hand sanitizing agents. As the review intended to emphasize efficacy specifically for SARS-CoV-2, the search of the literature focused on 2020 and early 2021 papers. The older literature was also searched for many of the topics described above, as papers specific to SARS-CoV-2 were not able to be identified in all cases.

The patient’s bodily fluids-hites-hands-mucous membrane nexus

Viral spread may also occur indirectly, following deposit of virus on HITES and then conveyed to susceptible tissues, such as mucous membranes (especially, the eyes, nose, and mouth), through the intermediacy of the hand (Fig. 1). This indirect route may be thought of as occurring through a patient’s bodily fluids-HITES-hands-mucous membrane nexus (Ijaz et al., 2020a). Respiratory and enteric viruses, such as influenza viruses, rhinoviruses, noroviruses, rotaviruses, adenoviruses, and coronaviruses, have been reported to persist (remain infectious) on HITES and prototypic surfaces for varying lengths of time (Scott et al., 2020). The persistence of SARS-CoV-2 on various types of surfaces may range from minutes to days (Aboubakr, Sharafeldin & Goyal, 2020; Ijaz et al., 2021b). This is also true for coronaviruses in general (Wolff et al., 2005; Aboubakr, Sharafeldin & Goyal, 2020; Kampf et al., 2020; Ren et al., 2020). Spore-forming bacteria (e.g., Clostridium difficile) and enteric parasitic cysts/(oo)cysts and ova have shown to survive on HITES under ambient conditions for weeks to months (Scott, Bruning & Ijaz, 2021). Additionally, enteric parasitic ova/(oo)cysts have been recovered from the hands of naturally contaminated Bangladeshi and Indian populations (Ijaz et al., 2013).

Various studies have reported the numbers of infectious units of different pathogens recoverable from contaminated hands of healthcare workers. For example, an investigation by Ehrenkranz & Alfonso (1991) reported that when gloves were not worn by healthcare workers, 15% of nurses working in an isolation unit carried a median of 10,000 colony-forming units of Staphylococcus aureus on their hands and 29% of nurses working in a general hospital had a median count of 3,800 colony-forming units. In another study (Daschner, 1989), 21% of doctors and 5% of nurses were found to carry > 1,000 colony-forming units of S. aureus on their hands. Casewell & Phillips (1977) found that nurses could contaminate their hands with 100–1,000 colony-forming units of Klebsiella spp. (Beggs, Shepherd & Kerr, 2008; World Health Organization, 2009; Awoke et al., 2018). Despite such evidence of the potential for healthcare workers to disseminate pathogens via contaminated hands, it has been estimated that these professionals practice hand hygiene fewer than half the time that they should (United States Centers for Disease Control & Prevention, 2011). Viruses have found to survive on experimentally contaminated hands, and secondary transmission to clean hands of other persons or HITES has been reported (Barker, Vipond & Bloomfield, 2004; Bidawid et al., 2004; Boone & Gerba, 2007; Winther et al., 2007; Kampf, Löffler & Gastmeier, 2009; Fong et al., 2020). In addition, in laboratory studies SARS-CoV-2 has been shown to survive on swine skin (a surrogate used for human skin, Harbourt et al., 2020) or human skin (Hirose et al., 2020), with a decay half-life of 3.5 to 9.0 h under ambient conditions.

These data inform the need for practicing hand hygiene per the recommendations of public health agencies, especially during the SARS-CoV-2/COVID-19 pandemic. According to the United States Centers for Disease Control & Prevention (2011) and the British Columbia Centre for Disease Control (2020), 80% of common infections are spread by hands, and washing hands at least five times a day has been shown to significantly decrease the frequency of acquiring colds, influenza, and other infections. In addition, hand washing helps prevent the spread of infectious agents to others. According to the United States Centers for Disease Control & Prevention (2020a), “keeping hands clean is one of the most important steps we can take to avoid getting sick and spreading germs to others.” Also, per the CDC (United States Centers for Disease Control & Prevention, 2020a), hand washing:

1. Reduces the number of people who get sick with diarrhea by 23–40%

2. Reduces diarrheal illness in people with weakened immune systems by 58%

3. Reduces respiratory illnesses, like colds, in the general population by 16–21%

4. Reduces absenteeism due to gastrointestinal illness in schoolchildren by 29–57%

The important roles that hands and HITES play in dissemination of pathogens are well established. This is especially true in the case of enteric viruses (enteroviruses, noroviruses, and rotaviruses). Gastrointestinal symptoms have also been reported for MERS-CoV, SARS-CoV, and SARS-CoV-2 (Kwan et al., 2005; United States Centers for Disease Control & Prevention, 2019; Caio et al., 2020; Wang et al., 2021). This indicates a potential for transmission through the oral-fecal route. In fact, the relevance of this route of transmission may have informed the public health agencies in recommending the hand hygiene intervention early on in the SARS-CoV-2/COVID-19 pandemic. There is a need for vigilance in maintaining appropriate hand hygiene practices, including the ancient and simple practice of washing hands with soap and water. With the availability of modern microbicides, disinfectants, sanitizing agents, and sanitizing hand rubs, it might not be clear why hand washing is still being recommended for infection prevention and control of SARS-CoV-2. We attempt to answer this question in the remainder of this article.

Handwashing with soap and water leads to inactivation and removal of pathogens

The use of soap followed by water rinsing is an effective intervention for decontaminating hands contaminated with enveloped viruses, such as SARS-CoV-2. Performed properly, hand washing with soap and water has important orthogonal mechanisms of action relevant to decontamination of hands (Chaudhary et al., 2020). The first of these is mechanical removal of dirt and organic load (such as mucus, sputum, other bodily secretions/excretions) to which virus may have adhered once released from an infected person. The removal function of soap and water is dependent on lathering and mechanical rubbing. Hand washing with soap and water accomplishes the physical removal of pathogens (including enveloped and non-enveloped viruses, bacteria, bacterial spores, and enteric parasitic ova and protozoan parasitic (oo)cysts) adhering to the skin. This physical removal also includes pathogens associated with dirt or organic or inorganic load, known as soil load (Sickbert-Bennett et al., 2005; Ijaz & Rubino, 2008; Grayson et al., 2009; World Health Organization, 2009; Conover & Gibson, 2016; Scott, Bruning & Ijaz, 2021). Soap in aqueous solution forms micelles. The ability of water to dissolve polar (hydrophilic) portions of the dirt or soil load is complemented by the ability of the soap micelles to dissolve the non-polar (hydrophobic) portions of the soil load and lipid-enveloped viruses (Fig. 2).

Once the polar and non-polar components of the dirt, soil load, and associated pathogens have been solvated, each of these may be physically removed through the lathering, rubbing, and water rinsing process. As will be alluded to below, it takes time for the solvation processes to occur, and time to effectively rinse the solvated components off of the hands. Guidance on duration of hand washing for at least 20–30 s (e.g., United States Centers for Disease Control & Prevention, 2020a; World Health Organization, 2009) reflects, in part, these realities.

The second orthogonal method of decontamination of hands by soap and water involves inactivation (reduction in infectivity) of enveloped viruses, including SARS-CoV-2. Compared with other microorganisms, enveloped viruses have a very simple structure (Fig. 3). All viral particles consist of genetic material (either DNA or RNA) that is enclosed within a protein structure termed a capsid. In the case of enveloped viruses, such as SARS-CoV-2, the capsid is covered with a lipid envelope derived from the host cell. Embedded in the lipid envelope are viral-encoded glycoproteins that enable the virus to interact with the appropriate host-cell receptor and initiate infection. For SARS-CoV-2, the primary host cell receptor has been reported to be angiotensin-converting enzyme 2 (ACE2) (Yan et al., 2020; Hoffmann et al., 2020).

Such receptor interactions confer specificity (tropism) for infecting the cells of certain animal species, or even certain tissues of a given animal species, as these interactions determine the ability of the virus to enter the cell and to initiate an infection of that cell, as described above.

Here is where the inactivating effects of soap enter the picture. The viral inactivation is primarily the consequence of disruption of the lipid envelope by the soap, as follows. Soap (and other detergents/surfactants) are capable of disrupting the continuity of the viral envelope, essentially through dissolving the envelope within and among the soap micelles (Fig. 4).

When the viral envelope is so disrupted, the host-cell receptor-binding ability of the virus is compromised and the virus can no longer initiate an infection. In this respect, enveloped viruses are actually the most susceptible of microorganisms to chemical inactivation (Ijaz & Rubino, 2008; Ijaz et al., 2020a). The inactivation by soap and water is no exception, and it is indeed fortunate, from a microbicidal susceptibility point of view, that SARS-CoV-2 and many other emerging and re-emerging viruses of public health concern (Ijaz et al., 2020a), are lipid-enveloped. Soaps or detergents (which by definition are surfactants-see below) begin to destabilize the lipid component of the envelope, leading to fragmentation of the lipid bilayer with embedded proteins. There is association of these fragments with surfactant monomers and possible micellization of these fragments, as well as of free proteins (Le Maire, Champeil & Møller, 2000; Simon et al., 2021), as depicted in Fig. 4.

Synergistic role of soap ingredients in removal and/or inactivation of pathogens

Soaps are sodium or potassium salts of long-chain (≥8 carbons) fatty acids, and are, by definition, surfactants. Surfactants are substances which lower the surface tension of the medium or the interfacial tension of solutions with mixed phases (e.g., aqueous/organic). Not all surfactants (surface active agents) are soaps (IUPAC, 1997). The biophysical and biochemical interplay between different soap components contributes to pathogen mobilization and removal, as well as to other characteristics of the formulated soap that include mildness and cleaning efficacy (removal of dirt, oils, and other bodily and environmental pollutants).

Antimicrobial soaps and their active ingredients

As explained above, the primary mechanisms of action for hand washing with soap and water include physical removal of free virus and virus-associated with dirt or other organic load from the skin, and inactivation of remaining enveloped viruses through disruption of their lipid envelopes. Antimicrobial (bactericidal and virucidal) soaps contain additional ingredients, such as benzalkonium chloride, benzethonium chloride, chloroxylenol, citric acid, lactic acid, or salicylic acid. Benzalkonium chloride, chlorhexidine, and chloroxylenol are effective against coronaviruses, in general (Kampf et al., 2020; Dev Kumar et al., 2020; Lin et al., 2020), and SARS-CoV-2, in particular (Chin et al., 2020). A liquid hand wash containing salicylic acid as active ingredient and a bar soap containing chloroxylenol have been reported to inactivate ≥ 3.0 log₁₀ of SARS-CoV-2 in 60 s (Ijaz et al., 2020b; 2021b). The addition of such agents to plain soap, in formulating antimicrobial soaps, should therefore add synergistic inactivation of an enveloped virus such as SARS-CoV-2 during hand washing. The inactivation of SARS-CoV-2 removed from the hands during washing and rinsing is an important topic, since the dissemination of infectious virus in waste water streams is undesirable from an infection prevention and control point of view. The potential for infectious SARS-CoV-2 to persist in wastewater streams is not empirically proven, although qPCR-based recovery of SARS-CoV-2 RNA in sewage has been reported (Peccia et al., 2020). This remains a significant knowledge gap that has yet to be closed (Mushi & Shao, 2020). There are data on the persistence of infectious virus in water for other coronaviruses, such as transmissible gastroenteritis virus, mouse hepatitis virus 1, and SARS-CoV (Aboubakr, Sharafeldin & Goyal, 2020), therefore it should be assumed that infectious SARS-CoV-2 may survive for some period of time in waste water.

Efficacy of plain and formulated soap for inactivating sars-cov-2 and other coronaviruses

To summarize the contributions of different components to the performance of plain and formulated soaps, efficacy must be achieved through a balance between microbicidal/virucidal efficacy and compatibility with the skin as a barrier and a critical component of defense against pathogens. This is of particular importance recently, as consumers wash and sanitize their hands more frequently as a response to the SARS-CoV-2 associated COVID-19 pandemic. Efficacy can often be improved through combinations of many of the components described above, including surfactants, chelators, pH adjusting agents, and microbicidal active ingredients which may potentially attack pathogens through multiple mechanisms of action. The finished soap product should also ensure that the skin barrier is protected, and that the pH of the skin is not adversely impacted. An assessment of the impact of the formula on the microbiota of the skin is also strongly recommended, as the microbial community may play an important role in skin’s ability to defend against pathogens.

In the above sections, we have described the mechanisms underlying inactivation of pathogens by soap and water washing. What evidence do we have of the actual virucidal efficacy of hand soaps against SARS-CoV-2 or other coronaviruses? In fact, there is a relative paucity of empirical data on this topic, as noted also by Mukherjee et al. (2021). This is true, despite the recommendations from the infection prevention and control community regarding the importance of hand hygiene with soap and water during the SARS-CoV-2 pandemic. More virucidal efficacy data for plain and formulated soaps need to be generated for SARS-CoV-2 and other enveloped viruses.

Chin et al. (2020) evaluated the efficacy of a diluted (1:49) hand soap solution in a suspension inactivation study and found that 15 or 30-min contact times each led to ≥3.0 log₁₀ inactivation of SARS-CoV-2, while a 5-min exposure did not completely inactivate the virus. Unfortunately, in the Chin et al. (2020) paper, full experimental details regarding the testing performed were not conveyed, especially the test method itself, the soap composition tested, and the techniques used for neutralization for mitigation of potential cytotoxicity from the soap prior to determining residual virus. These factors and others may have impacted the determined efficacy. Mukherjee et al. (2021) evaluated the efficacy of a bar soap for inactivating SARS-CoV-2. The soap was tested using the ASTM E1052-11 methodology (ASTM International, 2011) as an 8% w/v solution at 40 °C with 20 s contact time. Three different bar soaps of varying total fatty matter content each resulted in complete (≥3 to ≥4 log₁₀ inactivation). Ijaz et al. (2020b), Ijaz et al. (2021b) tested bar soap containing p-chloro-m-xylenol (tested at 0.014% w/w), reporting ≥ 4.1 log₁₀ inactivation of SARS-CoV-2 after a 30-s contact time, following the ASTM E1052-20 methodology (ASTM International, 2020) in the presence of a 5% fetal bovine serum organic load. Using the same methodology, these authors also evaluated a liquid handwash and a foaming hand wash containing salicylic acid (tested at ~0.025% final concentration) and a foaming hand wash containing benzalkonium chloride (tested at ~0.025% final concentration). These hand wash products (Table 1) caused ≥3.0 to ≥5.0 log₁₀ inactivation of SARS-CoV-2 and ≥3.3 log₁₀ to ≥3.6 log₁₀ inactivation of human coronavirus 229E after a 30 to 60-s contact time. In each case listed in Table 1, the inactivation of the coronavirus by the soap product was complete, meaning that no infectious virus could be recovered following exposure to the product. The log₁₀ reduction values shown were a function of the input viral titers and the limit of detection of the titration method used. The latter is impacted by the toxicity of the residual soap solution to the cells used for titrating the residual virus.

Why is adherence to the recommended contact time so critical?

As explained in detail above, the criticality of the recommended (20-s) handwash time is based both upon the removal and the inactivation functions of hand washing with soap and water. In the case of removal, it takes time to generate the lather required to solvate fats and oils, and to mobilize dirt from the skin surface (Jensen et al., 2017; Chaudhary et al., 2020). Once a pathogen associated with such bodily fluids or dirt has been solvated, it takes time to remove the solvated and mobilized (non-adherent) dirt, organic load, and virus from the skin through rinsing. Jensen et al. (2017) recommended a minimum lather time of 10 s, based on their studies with Escherichia coli. Rinsing time (~10 s) would then need to be added on to this lathering time.

The concept of the decimal reduction (D) value is important for considering contact time with soap for achieving viral inactivation. In other words, the inactivation of SARS-CoV-2 by soap is expected to be time-dependent. The time kinetics of inactivation of SARS-CoV-2 may or may not be first-order (i.e., log₁₀ reduction in infectious virus may not be linear with respect to time). This does not change the fact that a certain duration of time (lathering time, contact time, rinsing time) is required to achieve a desired extent of inactivation. Unfortunately, this topic has not been addressed empirically, to our knowledge, with the same rigor as has been applied to microbicides intended for application to inanimate hard or soft surfaces (fomites). That is, systematic determination of D values for inactivation of different viruses by soap and water were not found during our search of the literature, and this represents an area for future research. Lipid envelope-disrupting hand wash agents, as a class, appear to display efficacy after relatively short contact times. For instance, Ogilvie et al. (2020) found that QAC-based products inactivated SAR-CoV-2 in various soil loads within 15 s. Lavelle et al. (1989) showed that exposure to a hand wash product containing the phenolic p-chloro-m-xylenol caused concentration-dependent inactivation of human immunodeficiency virus (Retroviridae) suspended within a blood matrix within 30 s. The inactivation of Ebola virus Makona variant (Filoviridae) within a tripartite soil load (bovine serum albumin, tryptone, and bovine mucin) by a liquid hand wash agent also displayed concentration-dependent inactivation within 20 s contact time (Cutts et al., 2020a). Furthermore, disinfectant pre-impregnated wipes containing activated hydrogen peroxide or QAC have been shown to inactivate Ebola virus Makona variant and vesicular stomatitis virus (Rhabdoviridae) after a 5-s contact time (Cutts et al., 2020b).

Water temperature should not contribute to sars-cov-2 inactivation or removal during hand washing with soap

Viruses are susceptible to thermal inactivation. As a generality, the higher the temperature, the less time the virus will remain infectious, and this generality holds for emerging coronaviruses such as SARS-CoV (Duan et al., 2003), MERS-CoV (Leclercq et al., 2014), porcine epidemic diarrhea virus (Quist-Rybachuk, Nauwynck & Kalmar, 2015), and SARS-CoV-2 (Chin et al., 2020). The extent of inactivation by heating is dependent upon a number of factors, the primary ones being the specific virus under evaluation, the temperature, and the time at temperature. The susceptibility of SARS-CoV-2 to inactivation in culture medium was investigated recently by Chin et al. (2020). The experimental design included evaluation of the time kinetics of inactivation at a variety of temperatures (4, 22, 37, 56, and 70 °C), and inactivation was great enough at temperatures ≥ 22 °C to calculate decimal reduction values (D, defined as the duration of time required to cause 1 log₁₀ reduction in infectious titer).

The temperature susceptibility data mentioned above are only part of the answer. It also is important to consider the water temperature typically used (or expected to be used) for hand washing. According to the U.S. CDC (United States Centers for Disease Control & Prevention, 2020a) “The temperature of the water does not appear to affect pathogen removal; however, warmer water may cause more skin irritation and is more environmentally costly” (the references cited by CDC are Carrico et al. (2013) and Laestadius & Dimberg (2005)). On the other hand, the United States Food & Drug Administration (2005) requires that sinks used for hand washing in retail food settings be capable of supplying water at ≥38 °C (100 °F). The implication of this, though not formally stated, is that the U.S. FDA is recommending that hand washing for retail food preparation staff should be done using water at 38 °C. For the moment, let’s assume that the hand washing is done for the recommended 20 s (United States Centers for Disease Control & Prevention, 2020a) at 38 °C. What contribution to SARS-CoV-2 inactivation can we expect to achieve under these conditions? The first step in answering this question is to plot D vs. temperature and then calculate a power fit line. This has been done in Fig. 5, on the basis of the data published by Chin et al. (2020). It is apparent from this plot that at 38 °C, one would have to continue hand washing for over 250 min (the estimate from the fit line is 268 min) to achieve even one log₁₀ (90%) inactivation of SARS-CoV-2. At 55 °C, a temperature high enough to cause second-degree burns on skin in 30 s (Carrico et al., 2013), the D value for SARS-CoV-2 would be 6.3 min. Less time than this would, again, be essentially useless from an inactivation point of view. Taken together, these data demonstrate that the extent of heat inactivation of SARS-CoV-2 at 38 °C and 20 s contact time is insignificant, and the use of higher temperatures not only would not contribute to viral inactivation, but likely would have the undesirable effect of reducing the barrier properties of the skin.

What about the removal function of hand washing? It has been suggested that higher temperatures might enhance the dissolution of fat by soap and water. This might theoretically improve the dirt-, organic load-, and pathogen-removal function of hand washing. In a practical sense, however, water that is warm enough to be used for hand washing for the recommended period of time (~20 s) should be adequate from a pathogen (including SARS-CoV-2) removal point of view. In fact, Jensen et al. (2017) came to this conclusion in their studies on removal of Escherichia coli from hands during hand washing. They reported no significant difference in washing effectiveness at different water temperatures (from 15 to 38 °C). Based on their own data and those of several other investigators cited in their paper, Jensen et al. (2017) questioned the relevance of a required hand wash temperature of 38 °C, suggesting that this should be reconsidered. This conclusion was reached also by Michaels et al. (2002), using E. coli as the challenge microbe. Finally, the position of the WHO (World Health Organization, 2009) on this subject is that “Apart from the issue of skin tolerance and level of comfort, water temperature does not appear to be a critical factor for microbial removal from hands being washed. In contrast, in a study comparing water temperatures of 4, 20 and 40 °C, warmer temperatures have been shown to be very significantly associated with skin irritation. The use of very hot water for handwashing should therefore be avoided as it increases the likelihood of skin damage.” The reference cited for the skin irritation concern in the above WHO statement is Berardesca et al. (1995). From the above, it appears clear that the temperature of the water used for hand washing should be dictated by user comfort and not by concerns over impacts on pathogen removal or inactivation.

Even at temperatures deemed to be comfortable and to have less potential for skin irritation, the increased frequency of hand washing now being recommended in response to the SARS-CoV-2-associated COVID-19 pandemic might lead to some irritation of the skin in certain persons. According to Beiu et al. (2020) “Adverse dermatologic effects, such as excessive skin dryness or even contact dermatitis (particularly the irritant subtype and, to a lesser extent, the allergic subtype), can occur, especially in individuals with a history of atopic dermatitis. These skin conditions are perfectly manageable, and applying a moisturizer immediately after washing hands or after using a portable hand sanitizer is the cornerstone in preventing the development of eczematous changes in the hands. In the current global context, the potential occurrence of these dermatological adverse events should in no way cause people to deviate from strict hand hygiene rules.”

Drying of hands following hand washing

Hand drying is an essential component of effective hand washing that has not received as much attention as the washing process itself (Jumaa, 2005). It is known that the transmission of microorganisms is more effective in wet environments than in dry environments (Patrick, Findon & Miller, 1997). Drying of hands using touch-free electronic hot-air dryers has been touted, due to the fact that (in some cases) there is no need to touch a potentially contaminated surface to engage the drying action. There also are environmental sustainability reasons for advocating the use of such devices. While it might appear that there is less potential for skin abrasion when using hot-air drying devices, compared to the possible friction caused by use of a cloth or paper towel, use of hot-air dryers also may lead to dry, rough, and red hands (Huang, Ma & Stack, 2012). The proper use of a clean paper towel (patting the surface of the skin rather than rubbing it) can contribute to the removal function of hand washing, and does so in a manner which leads to less contamination of the washroom environment (Huang, Ma & Stack, 2012). This is because hot-air hand dryers can disperse pathogens into the air if the hand washing itself has been improperly practiced (Jumaa, 2005; Huang, Ma & Stack, 2012; Kimmitt & Redway, 2015; Del Carmen Huesca-Espitia et al., 2018; Suen et al., 2019; Gammon & Hunt, 2019). The potential for dispersion of infectious SARS-CoV-2 in restrooms by hot-air dryers has not been determined empirically. This, therefore, remains a research gap that needs to be resolved.

The roles of soap and water vs. hand sanitizers for sars-cov-2 decontamination

Hand sanitizers are an important hand hygiene intervention for skin contaminated with an enveloped virus such as SARS-CoV-2. Sanitizers are packaged in units that can be carried easily and therefore are able to be used in high-risk situations (e.g., following contact with high-touch environmental surfaces in public places) where the opportunity to wash hands with soap and water is not always possible. In addition, alcohol-based hand sanitizers appear to have less potential for causing skin irritation than do soaps (Gupta & Lipner, 2020; Rundle et al., 2020). One needs to be cautious, however, particularly with repeated use of hand washing with soap immediately before or after using an alcohol-based product under healthcare settings, as this practice could lead to dermatitis (World Health Organization, 2009). Therefore, we recommend that hand sanitizers not be used when soap and water hand wash facilities are available.

Alcohol-based hand sanitizers were found by Grayson et al. (2009) to be more effective than hand washing in reducing human influenza A virus on human hands, though both interventions were found to be effective. For disinfection of hands contaminated with SARS-CoV-2, a variety of types of hand sanitizers should be effective. These include alcohol-based sanitizers (≥60% ethanol or ≥70% isopropanol content is recommended per the U.S. CDC) (United States Centers for Disease Control & Prevention, 2020b). In general, lower concentrations of alcohols (~60%) are effective for inactivation of enveloped viruses, while higher concentrations (70% to 80%) are required for inactivation of non-enveloped viruses, such as hepatitis A and poliovirus (World Health Organization, 2009).

Golin, Choi & Ghahary (2020) have reviewed the efficacy of a variety of hand sanitizers against coronaviruses. These authors also reviewed the relatively limited empirical data obtained from studies directly comparing the efficacy of hand sanitizers vs. hand soaps for inactivating enveloped and non-enveloped viruses (Steinmann et al., 2012; Tuladhar et al., 2015). Steinmann et al. (2012) evaluated virucidal efficacy against enveloped viruses (vaccinia virus and bovine viral diarrhea virus) and non-enveloped viruses (poliovirus, adenovirus, feline calicivirus, and murine norovirus), comparing alcohol-based hand sanitizers with antimicrobial soaps in suspension testing and the fingerpad test with 30 s contact time. In the suspension testing method, the sanitizers were effective against all viruses, whereas the soaps were effective against the enveloped viruses only. In the fingerpad test, a povidone-iodine-containing soap was superior to the sanitizers, while the other soaps (containing chlorhexidine or triclosan) displayed less activity. In the Tuladhar et al. (2015) study, the virucidal efficacy of a propanol-based disinfectant against the non-enveloped murine norovirus was compared with that of soap and water. Soap and water washing was found to be superior to the propanol-based sanitizer, causing complete (≥3.0 ± 0.4 log₁₀) inactivation within 30 s, while inactivation by the alcohol-based sanitizer was incomplete and variable (2.8 ± 1.5 log₁₀) and required greater contact time (3 min).

The efficacies, for inactivating SARS-CoV-2, of three bar soaps and three alcohol-based hand sanitizers were compared in Mukherjee et al. (2021). Each resulted in complete (≥3 to ≥4 log₁₀ inactivation), though the test conditions were not the same. For instance, the bar soaps were tested as an 8% solution at 40 °C for 20 s, while the hand sanitizers were tested undiluted (as supplied), at 20 °C, for 10 or 15 s. Wolfe et al. (2017) compared the virucidal efficacy of soap and water vs. an ethanol-based hand sanitizer against the enveloped bacteriophage Phi6 (used as a surrogate for the Ebola virus) spiked onto human hands in the presence or absence of a soil load. In the absence of a soil load, the reductions in phage titer obtained following soap and water washing vs. use of the ethanol-based hand sanitizer were approximately equivalent (~2.5 log₁₀), while in the presence of a soil load, the efficacy of soap and water was superior (3.7 log₁₀ vs. ~2.5 log₁₀ for the hand sanitizer).

The comparison data mentioned above suggest that both hand sanitizers and soap and water display virucidal efficacy for enveloped viruses over short contact times (30 s). Hand washing with soap and water is recommended by the U.S. CDC (United States Centers for Disease Control & Prevention, 2020c) and the WHO (World Health Organization, 2009) when possible, since this hygiene practice achieves pathogen reduction both through removal and inactivation mechanisms, as alluded to above. This is in agreement with findings reported by Foddai, Grant & Dean (2016). In contrast, an alcohol hand rub (ABHR) or other type of hand sanitizer would be expected to inactivate but not necessarily remove infectious virus from the hands. As is the case for hand washing, the effectiveness of hand sanitizers is dependent on the contact time the active ingredient is in contact with the skin, and on the thoroughness of application of the sanitizer to all parts of the hand. According to the U.S. CDC (United States Centers for Disease Control & Prevention, 2020a):

• Alcohol-based hand sanitizers can quickly reduce the number of microbes on hands in some situations, but sanitizers do not eliminate all types of germs.

• Hand sanitizers may not be as effective when hands are visibly dirty or greasy.

• If soap and water are not available, use an alcohol-based hand sanitizer that contains at least 60% alcohol.

• When using hand sanitizer, apply the product to the palm of one hand (read the label to learn the correct amount) and rub the product all over the surfaces of your hands until your hands are dry.

Discussion

The recent outbreak of SARS-CoV-2 and its associated disease (COVID-19) emphatically has brought to the public’s attention the need for hand hygiene for interrupting the dissemination of the virus and for providing personal protection from becoming infected. We have attempted in this article to provide evidence for the unique utility of the relatively ancient practice of hand washing with soap and water for infection prevention and control during the current SARS-CoV-2/COVID-19 pandemic. The lessons learned from this exercise should be applicable to future outbreaks involving enveloped viruses, as the susceptibility of enveloped viruses is similar, whether one is considering the influenza virus, SARS-CoV-2, or the Ebola virus (Ijaz & Rubino, 2008; Ijaz et al., 2020a). In addition, there are a number of categories of pathogens which exhibit similar susceptibilities to chemical microbicides such as detergents and alcohols. These include vegetative bacteria, yeasts and non-filamentous fungi.

Hand washing is an important intervention for infection prevention and control of viral infections. This is due to the fact that infectious viruses, whether displaying tropism primarily for the upper respiratory tract (e.g., rhinoviruses, coronaviruses, and influenza viruses), or for the gastrointestinal tract (e.g., reoviruses, enteroviruses, and enteric caliciviruses such as human norovirus) ultimately are spread, in large part, through the intermediacy of the hand (as shown in Fig. 1). While a respiratory infection can be caused by direct inhalation of infectious virus-containing aerosols, dissemination of the virus often involves the intermediacy of the hand. The hands can convey infectious virus from a contaminated surface to the mucous membranes of the eye, nose or mouth, thereby predisposing to the initiation of a new infection in a previously healthy person.

The fecal-oral route, which applies primarily to enteric viruses, also depends on hands as the vehicle for infection of a new host. Recently, Tang et al. (2020) reported an asymptomatic child whose stool sample tested positive for SARS-CoV-2 RT-PCR 17 days after virus exposure. The child was virus positive in stool specimens for at least an additional 9 days. Respiratory tract specimens were negative. Since this report, SARS-CoV-2 has been recovered from stool samples using infectivity assays (Zhang et al., 2020), demonstrating the presence of infectious virus. These results highlight the potential for virus dissemination during changing diapers, and call for practicing appropriate hand and surface hygiene practices by parents of infants. The results also suggest that a combined/paired hygiene approach proposed by Lei et al. (2020) for intervention of pathogens should be applicable to SARS-CoV-2 dissemination from fomites. Additionally, frequent HITES decontamination using surface care disinfectants and wipes, is necessary, particularly when someone is infected with SARS-CoV-2 in a household. This includes such HITES as diaper changing areas, bathroom surfaces, toilet lids, door knobs, etc. Appropriate toilet and kitchen hygiene also must be practiced (Meng et al., 2020).

Why do the hands play such an important role in spread of viruses (and other pathogens)? By habit, we frequently touch our face, including mucous membranes of the nose, eye, mouth. For instance, it has reported (Kwok, Gralton & McLaws, 2015) that we touch our face on an average 23 times per hour (44% touching of a mucous membrane and 56% touching of non-mucosal areas). The mucous membranes touched include the mouth (36%), nose (31%), eyes (27%), and all combined (6%) (Kwok, Gralton & McLaws, 2015). This frequent touching of facial mucous membranes is believed to be taking place in the case of COVID-19, hence the emphasis on hand hygiene by the infection control communities and public health agencies.

The limitations of this review include the following. As the SARS-CoV-2 pandemic has been a relatively recent occurrence, literature addressing certain topics may be limited. This included mechanisms of action of soap and water for removal and inactivation specifically of SARS-CoV-2, efficacy of plain soaps for inactivation or removal specifically of SARS-CoV-2, and contribution of soap components (including microbicidal components) to inactivation or removal specifically of SARS-CoV-2. In some cases, we have had to discuss information for other enveloped viruses or for vegetative bacteria or parasites, recognizing that efficacy for the latter is generally informative for SARS-CoV-2 as well. Finally, there are little clinical data to support the utility of hand washing in preventing acquisition of SARS-CoV-2 or other coronaviral infections (e.g., Fung & Cairncross, 2006). Several trials focusing on hand washing have been carried out (Luby et al., 2005; Cole et al., 2012). A very recent literature review revealed that hand-washing reduces diarrhea episodes in child day-care centers in high-income countries and among communities living in low-and middle-income countries by ~30%. The reviewed trials did not provide evidence of the long-term impact of the interventions, however (Ejemot-Nwadiaro et al., 2021) and this topic deserves further investigation. In particular, we are not aware of clinical trials which have been able to focus specifically upon the benefit of hand washing while ruling out other confounding interventions, such as surface hygiene, mask wearing, and social distancing. Other knowledge gaps have been discussed within the body of this review.

We have attempted to clarify certain questions that might come up regarding the need for hand hygiene, the mechanism of action of hand washing with soap and water, the importance of lathering, rubbing, and soap contact time and water temperature during hand washing, the possible synergistic role of active ingredients formulated into hand soaps, the impact of different hand drying methods that might be used post-hand washing, and the potential role of hand washing along with hand sanitizing agents in infection prevention and control during the current SARS-CoV-2/COVID-19 pandemic. It is hoped that this discussion will not only be useful for infection prevention and control during the current SARS-CoV-2/COVID-19 pandemic, but also during future outbreaks involving emerging/reemerging enveloped viruses and variants such as the alpha, beta, delta, gamma, and lambda variants of SARS-CoV-2 (United States Centers for Disease Control & Prevention, 2021).