Shifting Approach to Environmentally Mediated Pathways for Mitigating COVID-19: A Review of Literature on Airborne Transmission of SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has been confirmed in over 10,000,000 individuals worldwide and has resulted in more than 500,000 deaths in a few months since it first surfaced. With such a rapid spread it is no surprise that there has been a massive effort around the world to collectively elucidate the mechanism by which the virus is transmitted. Despite this, there is still no definitive consensus regarding droplet versus airborne transmission of SARS-CoV-2. Public health officials around the world have introduced guidelines within the scope of droplet transmission. However, increasing evidence and comparative analysis with similar coronaviruses, such as severe acute respiratory syndrome (SARS-CoV-1) and middle eastern respiratory syndrome (MERS), suggest that airborne transmission of SARS-CoV-2 cannot be effectively ruled out. As the data supporting COVID-19 airborne transmission grows, there needs to be an increased effort in terms of technical and policy measures to mitigate the spread of viral aerosols. These measures can be in the form of broader social distancing and facial covering guidelines, exploration of thermal inactivation in clinical settings, low-dose UV-C light implementation, and greater attention to ventilation and airflow control systems. This review summarizes the current evidence available about airborne transmission of SARS-CoV-2, available literature about airborne transmission of similar viruses, and finally the methods that are already available or can be easily adapted to deal with a virus capable of airborne transmission.


INTRODUCTION
On March 11th, 2020, coronavirus disease 2019  was designated by the World Health Organization (WHO) as a pandemic. It has since been confirmed in over 10 million cases worldwide and has resulted in more than 500,000 deaths. [1] Despite the widespread investigation of COVID-19, many aspects of the disease such as the severity, demographic preference, and transmission of the disease, are still under contention. The Centers for Disease Control and Prevention (CDC) characterizes the transmission of infectious agents via three mechanisms: direct or indirect contact, droplet, or airborne route.
[2] While efficient human to human transmission of COVID-19 is undisputed, [3] the extent of this mode of transmission has yet to be fully confirmed. Current guidelines from the WHO and CDC have resigned to treat COVID-19 as a droplet transmitted disease, thereby recommending facial coverings and a distance of 2 meters between individuals. [4,5] However, analysis of previous coronaviruses, increasing evidence by way of case study, and incoming, but limited, empirical data shows that not only are droplet precautions inadequate, but airborne precautions merit aggressive implementation. [6,7,8] There is commonly known evidence related to the aerosol transmission of various viral pathogens, such as Influenza virus, Rhinovirus, Adenovirus, Measles virus, Respiratory Syncytial virus, and Ebola virus. Of more importance, is the wealth of evidence concerning coronaviruses such as SARS-CoV and MERS. Given the high level of genetic conservation between the novel SARS-CoV-2 and previously studied coronaviruses, [9] there is mounting reason to infer that SARS-CoV-2 may also be distributed via aerosol transmission. Transmission via airborne particles 5 micrometer (μm) or less in size from asymptomatic carriers can help understand the unprecedented spread of this novel disease. [10] Although the current evidence regarding airborne transmission needs to be interpreted with caution, it should at least encourage the adoption of simple measures that can mitigate aerosol dispersion. At a general population level, the use of face masks should be universal, as it has been associated with a decline in new cases where implemented. [11] Resourceful attempts have been made to repurpose surgical personal protective equipment (PPE), but to our knowledge, none have been successful in preventing the inhalation of potentially virulent aerosols. [12] Because of the documented susceptibility to heat of coronaviruses, [13] promising strides have been made in deactivating COVID-19 by applying high, yet tolerable, temperatures to the upper respiratory tract. [14] Because of the potential of ultraviolet light, particularly type C (UVC), in deactivating pathogenic microbes [15][16][17], low dose UVC is a candidate for widespread implementation in hospitals, doctors' offices, and other high-risk areas [18]. Lastly, properly designed ventilation systems inside buildings can be an effective tool to curtail airborne infection.
Inventive approaches to developing portable, low cost, negative pressure systems are beginning to appear regularly. [19,20] Critical elements of ventilation that influence airborne transmission include ventilation rate, flow direction, and airflow pattern. [21] The objective of this review has been to explore and summarize the rapidly emerging literature regarding airborne transmission of SARS-CoV-2, the available literature regarding airborne transmission of related viruses that have been involved in previous outbreaks, and finally the methods and technologies that are already available or can be easily adapted to deal with a virus capable of airborne transmission.

Transmission of Viral Pathogens
The CDC characterizes the transmission of infectious agents via three mechanisms: direct or indirect contact, droplet, or airborne route.[2] Direct or indirect contact involves transmitting the pathogen from one person to another with or without a contaminated intermediate, respectively. [22] Droplet transmission involves the expulsion of droplet particles, 5 µm or greater in diameter, from the respiratory tract. These projected droplets can directly settle on the mucosae of an exposed individual or they can reside on surfaces, such as door knobs, to be picked up later by hand. [23] In contrast, airborne transmission results from the inhalation of droplet nuclei. These small particles are distinguished by having a diameter of 5 μm or less. Notable infectious agents that spread via the airborne route include Influenza, Measles, and Tuberculosis, among others. [23] The formation of infectious bioaerosols, in the general public, are linked to multiple processes such as expiratory activities of humans, showering or use of tap water, sewage aerosolization from toilets, and sewage transport through pipe systems, wet-cleaning of indoor surfaces, and agricultural spraying of 'gray' water. [24] Aerosol formation in healthcare settings, as listed by the CDC, is possible via specific procedures such as open suctioning of airways, sputum induction, cardiopulmonary resuscitation, endotracheal intubation and extubation, noninvasive ventilation (e.g., BiPAP, CPAP), bronchoscopy, and manual ventilation. [5] Currently, the WHO applies the greater or less than 5 μm size of droplet nuclei to differentiate between droplet transmission and airborne transmission. [25] However, this dichotomy comes with limitations.
Particles capable of projecting from the respiratory tract and being inhaled by a susceptible individual can be both greater and lesser than 5 μm in size. Aerosol plumes generated from coughing, sneezing, or speaking, can range from less than 0.1 μm to greater than 100 μm and lodge directly into airway, tracheobronchial, or alveolar locations. [26] These aerosols are capable of remaining suspended in gas or air for extended periods. Furthermore, a recent review by Bahl et al. addresses various studies exploring horizontal droplet distance by presenting evidence that infectious particles may travel distances up to 26 feet. [4] While large droplets may typically settle within 3 to 6 feet of an individual, other smaller droplets are capable of remaining suspended, traveling through a room or to other rooms, and landing 20 to 26 feet away. [27] There is already ample evidence related to the aerosol transmission of common viruses, such as Rhinovirus, Adenovirus, Measles virus, Respiratory Syncytial Virus, and Ebola Virus. [28][29][30][31][32] Indeed, literature regarding the aerosol transmission of Influenza virus and Coronavirus has become extensively available following the 2003 outbreak of SARS-CoV-1. [33] In the case of Influenza virus, a study by Francoise et al. confirmed the presence of airborne transmission by collecting aerosol samples in different areas of an emergency department. Their study found that, throughout the healthcare environment, airborne virus particles were present, and approximately 53% of these particles were 4 μm in size or below. [34] In the case of MERS, a viral presence was found in 4 of 7 air samples from 2 patient rooms, a patient restroom, and a common corridor. Given the high level of genetic conservation between the novel SARS-CoV-2 and the viruses mentioned above-particularly MERS and SARS-CoV-there is mounting reason to infer that SARS-CoV-2 may also be distributed via aerosol transmission. [9]

Evidence/Characteristics of SARS-CoV-2 Airborne Transmission
Recent literature has suggested that an increasing number of SARS-CoV-2 cases occur via inhalation of aerosols produced by asymptomatic carriers. Indeed a small but growing number of case reports are beginning to appear in support of airborne transmission. [8] Many of these reports originate in China, which experienced a high caseload early in the pandemic, while a few high profile "superspreading" events appear in the United States. [43][44][45][46] Of note, was a choir practice event that resulted in 45 of 60 choir members being infected. [45] Interestingly, choirs have been linked to multiple outbreak events in the United States, possibly due to both an increase in droplet projection and an increase in droplet nuclei dissemination through aerosolization. [47] These "superspreading" events are likely the result of a few asymptomatic individuals, presumably in the early pharyngeal shedding stage, expelling aerosolized droplet nuclei while simply speaking or breathing. As asymptomatic individuals, it is less likely that these "silent shedders" are coughing or sneezing at a rate to justify only droplet transmission. [10] A plausible explanation for their high infectivity lies in the ability of SARS-CoV-2 to aerosolize in droplets smaller than 5 μm. Indeed, a study by Leung et al. showed that seasonal coronaviruses were more commonly emitted as aerosols, even in ordinary tidal breathing. [48] Furthermore, it is estimated that merely 1 minute's worth of loud speaking, let alone singing, could create over 1000 virion-containing aerosol particles. [49] A report published by Li et al., found that 79% of SARS-CoV-2 cases in China were via an asymptomatic carrier, which makes it unlikely that they were producing large infectious droplets and further support aerosolization as a mechanism for the transmission of SARS-CoV-2. [50] As stated in a commentary of aerosolized transmission by Anderson et al., little empirical data exists, and a broader initiative is needed regarding the exact aerodynamics of SARS-CoV-2 airborne transmission. [8] This is bolstered by a statement made by the National Academy of Science that while little SARS-CoV-2 specific research is available for airborne transmission, the current studies comply with the idea that the virus is aerosolized via normal tidal breathing. [51]

Mitigation of Airborne Transmission
Methods to mitigate the spread of infectious SARS-CoV-2 aerosols are wide-ranging in ease, time, cost, and universality of implementation. Currently, the CDC, WHO, and European Centre for Disease Prevention and Control have issued guidelines primarily intended to limit the spread of SARS-CoV-2 droplets. [4] While the CDC has recommended precautions for airborne transmission, it only advocates for them in healthcare settings during aerosol-generating procedures. [5] For the general public, a 2-meter spatial separation is recommended to limit the possibility of droplet transmission. Unfortunately, even droplets (> 5 μm) have been shown to spread up to 8 meters, [4,52] suggesting that the current recommendation of 2-meter distance may have limited effectiveness even for droplet transmission.

Methods of Viral Inactivation
One pathway to eliminate aerosol transmission of SARS-CoV-2 is available via heat inactivation.  characteristics will find a place in future pandemics.

Data Availability
No data are associated with this article