Preface

The ongoing (as of April 4, 2022) pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to engage the infection prevention and control (IPAC) and research communities. To date, the pandemic has resulted in 492 million cases globally and more than 6 million deaths [1]. As might be expected, the pandemic has resulted in an unprecedented volume of publications on IPAC topics for this virus and its associated disease, COVID-19. As such, we thought that a collection of articles on viral disinfection might be timely. First, a little background. Viruses are not capable of reproducing themselves. Animal viruses, for instance, require a eukaryotic host cell to propagate and produce progeny. As a result, viruses are not considered "alive" or "dead"; rather, they simply are infectious or non-infectious. Disinfection of viruses is intended to render the viruses non-infectious (i.e., inactivate them), and the terms "virucidal efficacy" and "efficacy of viral inactivation" are commonly employed to denote the capability of a chemical disinfectant (e.g., alcohol) or a physical approach (e.g., ultraviolet light) for rendering a virus non-infectious. The most straightforward way to express virucidal inactivation efficacy is to state the log10 reduction in titer for the virus from the initial state to the post-treatment state. A commonly sought goal for an effective viral disinfectant (virucide) is to achieve at least a 3-log10 inactivation [2]. This equates to rendering 99.9% of the initial virus population non-infectious [3]. Of course, a 3-log10 virucidal efficacy, by itself, does not ensure safety under every circumstance [4], as this may depend on the initial virus titer, the human infectious dose (reported to be as low as 10 TCID50/mL for SARS-CoV-2 [5]), susceptibility factors for the host, and the lethality of the contaminating virus. However, it is very important to note that when one describes virucidal effectiveness for a chemical disinfectant or a physical approach, one must be specific about the exact virus being disinfected (as efficacy may vary for different viruses), and the approach for disinfection (i.e., disinfection in liquid suspension, disinfection of surfaces, sanitization of hands, etc.). In addition, for many disinfection approaches, other factors come into play. These may include temperature, pH, relative humidity, presence of associated organic (soil) load, and contact time. Descriptions of virucidal efficacy, therefore, must include all this information for maximal utility to readers.

Disinfection is an important part of infection prevention and control. Most importantly, sanitization of hands and disinfection of liquids and surfaces is intended to interrupt the chain of infection, through the intermediacy of the hand, from an infected individual to an otherwise healthy individual, as depicted in **Figure 1**.

The term "targeted disinfection" is employed when chemical disinfectants or physical agents are applied strategically to high-risk surfaces (high-touch environmental surfaces [HITES]) (**Figure 2**), thereby avoiding indiscriminate use of disinfectants/agents and adverse impacts on the microbiome of the built environment [4].

#### **Figure 1.**

*Interrupting the chain of infection using targeted disinfection/sanitization (hygiene) approaches (from Scott et al. [4]).*

#### **Figure 2.**

*High-risk surfaces and activities for viral spread to the hand, leading potentially to risk of infection dissemination to a susceptible host (from Scott et al. [4]).*

Disinfection approaches are not only used for IPAC in healthcare settings and in everyday settings (homes, community, workplaces, etc.) specifically, but are also used in the pharmaceutical/biopharmaceutical industries for cleaning surfaces, disinfecting liquid waste, as barrier treatments for pathogen reduction in raw

materials and process streams, and for "viral clearance" inactivation steps to assure the viral safety of products. In addition, disinfection is used in laboratory settings to render biological specimens safe for handling.

A common theme that runs throughout this book (*Disinfection of Viruses*), either implicitly or explicitly, is the concept of the hierarchy of pathogen susceptibility to microbicides. This concept was first developed by E.H. Spaulding [6], further refined by M. Klein and A. Deforest [7], S.A. Sattar [8], M.K. Ijaz and J.R. Rubino [9], and eventually incorporated into regulatory guidance by the US Environmental Protection Agency (US EPA) [10, 11]. The concept is based on the observation that different classes of pathogens differ with respect to their relative susceptibilities to the inactivating effects of chemical microbicidal active ingredients. In the most recent version of the hierarchy, infectious proteins (prions) represent the least susceptible of pathogens, while the other extreme (most susceptible) is represented by enveloped viruses (**Figure 3**). The utility of this concept, recognized by the US EPA and implemented in several guidance documents [e.g., 10, 11], is that it enables predictions to be made as to the types of microbicidal actives that might be expected to inactivate (render non-infectious) an emerging pathogen.

The US EPA's Emerging Viral Pathogens Policy was activated during the 2009 H1N1 influenza A virus pandemic [12], during the 2015 Ebola virus outbreak [13], and again in response to the SARS-CoV-2/COVID-19 pandemic in 2020 [14].

#### **Figure 3.**

*Hierarchy of susceptibility of pathogens to microbicidal active ingredients ([15] modified from Sattar [8]).*

Why is this important? It takes time (1) to isolate the wild-type pathogen, such as a novel virus, from the field and establish a laboratory culture; (2) to prepare stocks of the emerging pathogen to be made available to the research community; and (3) for the research community to conduct the studies needed to confirm the expected inactivation efficacy of various types of microbicides. For especially lethal pathogens, such as hemorrhagic fever viruses, only BSL-3 or BSL-4 laboratories may be capable of performing such activities. During the intervening period of time between emergence of a novel pathogen and the confirmation of inactivation efficacy of available microbicides, the US EPA guidance, based on the pathogen susceptibility hierarchy concept and virucidal efficacy data available for other variants, other family members, or appropriate surrogate pathogens, facilitates decision making on the types of microbicidal actives that will be useful in disinfecting surfaces and solutions, and sanitizing hands in the face of the novel pathogen outbreak.

Each of the chapters in this book touches on virucidal efficacy for the SARS-CoV-2 virus or enveloped viral surrogates. Per the pathogen susceptibility hierarchy concept, SARS-CoV-2, an enveloped virus of the *Coronaviridae* family, is expected to be susceptible to all classes of microbicides [15]. Evidence of this is provided within the various chapters of this book.

Section 1: "Microbicides for Viral Inactivation," contains three primary reports and three review articles. In Chapter 1, Nishihara et al. describe [16] the efficacy of a silver ion formulation for inactivating SARS-CoV-2, and the non-enveloped feline calicivirus (used as a surrogate for human norovirus), in suspension studies. In Chapter 2 [17], Lee and Henneman discuss a "Dry Hydrogen Peroxide" approach for inactivating the enveloped influenza A (H1N1) virus, and the non-enveloped feline calicivirus and MS2 bacteriophage, on surfaces or in air. In Chapter 3, Hislop, Grinstead, and Henneman describe [18], a "Hybrid Hydrogen Peroxide" approach for inactivating SARS-CoV-2, as well as a variety of other enveloped and non-enveloped viruses and bacteriophage, on surfaces. Chapter 4 [19], by Ikner and Gerba, provides a review of the efficacy of antiviral surface coatings for inactivating SARS-CoV-2 and a variety of other enveloped and non-enveloped viruses. In Chapter 5, Ijaz et al. [20] take advantage of the pathogen susceptibility hierarchy concept to predict the virucidal efficacy of microbicides against emerging and re-emerging viruses called out in the World Health Organization's 2021 Priority Disease List [21], then review the empirical data for virucidal efficacy of microbicides for the specific viruses mentioned in the list. Finally, Chapter 6 [22], by S.S. Zhou, provides a review and commentary on the application of the pathogen susceptibility hierarchy concept to the non-enveloped class of viruses.

Section 2: "Physical Inactivation Approaches," begins with Chapter 7 by Nims and Plavsic [23]. This chapter reviews the efficacy data for physical approaches (gamma irradiation, UVC irradiation, and heat) for inactivating SARS-CoV-2 and other coronaviruses.

Section 3: "Viral Persistence and Disinfection," includes a review and commentary in Chapter 8 by K. Ranjan [24] of the data on viral persistence for SARS-CoV-2 on porous and non-porous surfaces, and in liquids and air, as these data inform the need for and the approaches that might be used for disinfection of environmental surfaces, air, and wastewater in healthcare and non-healthcare settings.

The editors appreciate the time taken by the various authors to contribute to this book. It is hoped that the assembled articles will provide value to the IPAC, research, and pharmaceutical/biopharmaceutical communities during the ongoing SARS-CoV-2 pandemic and during future viral outbreaks, which undoubtedly will occur! The editors also appreciate the patient assistance of the staff at IntechOpen, Zrinka Tomicic, Kristina Kardum Cvitan, and Lucija Tomicic-Dromgool.

> **Raymond W. Nims, Ph.D.** RMC Pharmaceutical Solutions, Inc., Longmont, CO, USA
