Transmission of SARS-CoV-2
This chapter includes an overview of the viral transmission and the phases of infection before providing specifics about SARS-CoV-2. Following the description of SARS-CoV-2 transmission dynamics, the next section will focus on the subject of masks, a topic that has been ubiquitous within COVID-19 discourse. Transmission follows the chain of infection, which begins with a pathogenic agent being released from a reservoir that eventually travels through a portal of exit. The pathogen is then conveyed by a mode of transmission before it infects a susceptible host via a portal of entry (see Figure 2.1). Laypersons and clinicians who would like a brief refresher will benefit from reviewing sections Reservoirs and Hosts, Routes of Transmission, Portals, and Phases of Infection.
Reservoirs and Hosts
A viral reservoir is an organism in which a virus lives, grows, and multiples. In some cases, a reservoir may harbor a virus and be clinically affected by the infection. In other cases, a reservoir may harbor a virus and be capable of transmitting it even if it may not show symptoms of infection. This may be because symptoms have yet to appear or because the individual has an asymptomatic infection, in which case that individual is known as a carrier. Entire species may harbor a virus and only develop limited clinical disease when infected. When this occurs, the organism is known as a reservoir host. Bats, for example, frequently serve as reservoir hosts and have been associated with more zoonotic viruses than any other mammalian order.1
 Figure 2.1 The chain of infection. (Centers for Disease Control and Prevention. Principles of epidemiology. 2nd ed. Atlanta: U.S. Department of Health and Human Services;1992. Reference to specific commercial products, manufacturers, companies, or trademarks does not constitute its endorsement or recommendation by the U.S. Government, Department of Health and Human Services, or Centers for Disease Control and Prevention.) |
There are potentially trillions of virus species and an estimated 1031 individual virions on Earth. Luckily, only an infinitesimally small percentage of them pose any threat to humans.2 Most viruses have a limited host range, meaning they have adapted to infect only a handful of species very well. Hosts are only susceptible to infection if the virus can access cells that express receptors to which the virus can bind (see Chapter 1, Section Viruses). Cells must also be permissive to infection, meaning they contain the intercellular mechanisms necessary to allow for viral replication and assembly. Tissue tropism refers to the cell types within an organism that a virus targets and uses for replication. Some viruses have demonstrated a broad tropism and can infect many kinds of cell tissues in multiple organs, while other viruses are more specific and only attack a narrow range of tissue types.
When a virus does manage to make the jump between an animal and a human, this is known as a spillover event. A disease that infects people by way of animals is known as zoonosis. Spillover events appear to be relatively common, but most cross-species infections are either transient or abortive.3 In other words, individual spillover events may lead to an infection and even a disease within a human host, but the virus is often incapable of then spreading to other humans. When a virus jumps from an animal reservoir to a human host on several separate occasions without resulting in human-to-human transmission, it is known as viral chatter.4
There have been at least two instances of limited viral chatter involving coronaviruses in the past 5 years. Surprisingly, neither has received a great deal of attention in the media. One was a canine-feline recombinant alphacoronavirus that infected at least eight individuals in Malaysia and caused cases of pneumonia from which all patients recovered.5 The other, described in a preprint article, was a deltacoronavirus that appears to have jumped from pigs to three children in Haiti and caused acute undifferentiated febrile illness.6
Routes of Transmission
Viruses can be spread through direct or indirect means and often through multiple routes (or modes) of transmission. Direct transmission includes person-to-person contact and large droplet spread. Indirect transmission occurs when there is an intermediary in the chain of infection and intermediaries can include dust or aerosolized particles that are smaller than droplets. It can also include vehicles (objects like food, water, or surfaces [fomites]) or vectors, which are organisms that carry and transmit pathogens into another organism (mosquitos, ticks, fleas, etc).
It should be noted that the distinction between droplets and aerosols (see Figure 2.2) is not categorical, but rather determined by particle size (typically 5 microns [µm]), and that there is some debate about the cutoff mark between the two. However, droplets are usually defined as large particles and greater than 5 µm. Moreover, particles that fall in the twilight
between aerosol and droplet can behave a bit like both. To elaborate, particles in the range of 5 to 20 µm are not only capable of lingering in the air for longer than their larger counterparts; they have also demonstrated some ability to penetrate deep into the alveolar tissues of the lower respiratory tract.7 Despite these concerns, the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) have both maintained that the lower limit for droplet size is 5 µm.7
between aerosol and droplet can behave a bit like both. To elaborate, particles in the range of 5 to 20 µm are not only capable of lingering in the air for longer than their larger counterparts; they have also demonstrated some ability to penetrate deep into the alveolar tissues of the lower respiratory tract.7 Despite these concerns, the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) have both maintained that the lower limit for droplet size is 5 µm.7
 Figure 2.2 When viruses are shed from the respiratory tract of an infected individual, they may be transmitted by multiple routes. This illustration shows how the virus may be spread via aerosolized particles and larger droplets that tend to be quickly pulled down by gravity. (Illustration courtesy of Zhang R, Li Y, Zhang AL, Wang Y, Molina MJ. Identifying airborne transmission as the dominant route for the spread of COVID-19. PNAS. 2020;117(26):14857-14863. doi:10.1073/pnas.2009637117) |
Person-to-Person
Contact Person-to-person transmission occurs when a pathogen is spread from one person to another. Person-to-person contact is when an infection occurs following physical contact with an infected person. Transmission may occur when body fluids are exchanged or through skin-to-skin contact. Sexually transmitted diseases represent the most notorious examples of pathogen spread through person-to-person contact but are by no means the only ones. Human rhinoviruses, for example, have been shown to spread very efficiently following hand-to-hand contact.8
Droplet
Droplet spread occurs when an individual has a respiratory infection and expels virions while talking, coughing, sneezing, or singing.9 These virions travel within large droplets (>≈5 µm), and the distance and length of time they remain in the air depends on several factors, particularly relative humidity and temperature. Larger particles from the respiratory tract have been shown to travel farthest in environments with low temperatures and high levels of relative humidity.10
When an individual coughs or sneezes, very large droplets (measured in millimeters instead of microns) rarely travel more than 2 m. Consequently, many social distancing guidelines that were put in place recommended that people remain 2 m or 6 ft apart to prevent the spread of the coronavirus, which was initially believed to be transmitted primarily via large respiratory droplets.
Smaller droplets (ranging from 5 to 1000 µm) are capable of traveling beyond this range and in cool and humid conditions may travel up to 4.5 m (14.7 ft) or 8 m (26 ft) when an infected individual either coughs or sneezes, respectively.7 It should be noted, however, that approximately 95% of virions carried by respiratory droplets travel 1.4 m (4.5 ft) or less even in extremely cool and humid conditions and that ventilation matters.10 In outdoor settings, droplets dissipate relatively quickly, thereby making the risk of infection via this mode of transmission relatively low, particularly if individuals are more than 2 m apart. Risk is significantly higher when indoors, especially if the area is not well ventilated and is cool and damp. A preprint study found the odds of a primary case transmitting SARS-CoV-2
in a closed environment to be 18.7 times higher than in an open-air environment.11 (In addition to dispersing the virus, being outdoors in the sunlight may be safer than the indoors because simulated sunlight has been found to inactivate SARS-CoV-2 in a matter of minutes.12)
in a closed environment to be 18.7 times higher than in an open-air environment.11 (In addition to dispersing the virus, being outdoors in the sunlight may be safer than the indoors because simulated sunlight has been found to inactivate SARS-CoV-2 in a matter of minutes.12)
Infection occurs when virions are inhaled or make direct contact with mucous membranes (see Portal of Entry). In some cases, droplets from an infected individual may contaminate another individual’s hands, and then cause infection if that person touches their eyes, nose, or mouth (hence the reason why good hand hygiene is so important). Droplets may also land on and contaminate surfaces. These contaminated surfaces are referred to as fomites.
Viruses typically do not survive on skin for very long. A sample of influenza A virus was found to survive for approximately 1.82 hours on a sample of human skin, while the same study showed that the SARS-CoV-2 virus survived on human skin for an average of 9 hours.13 SARS-CoV-2 and influenza A virions have been shown to remain viable on stainless steel for upward of 72 hours.14, 15
Airborne
Like droplet spread, airborne spread occurs when an infected individual expels virions while talking, singing, coughing, or sneezing, but this is not the sole manner in which aerosols are released. Certain medical procedures and fast-running water (particularly after toilet flushes) can produce aerosols, and these aerosols can provide a means of conveyance for virions. According to a scientific brief published by the WHO, medical procedures that can produce aerosols include “endotracheal intubation, bronchoscopy, open suctioning, administration of nebulized treatment, manual ventilation before intubation, turning the patient to the prone position, disconnecting the patient from the ventilator, noninvasive positive-pressure ventilation, tracheostomy, and cardiopulmonary resuscitation.”16
As is the case with droplet transmission, the range of smaller, virus-laden particles is also affected by environmental conditions, but conversely, they spread farthest when temperatures are high and humidity levels are low.10 They can also linger in the air for a matter of hours. SARS-CoV-2, for example, was found to remain viable in the air for 3 hours and to have a half-life as an aerosol of 1.1 hour.15
Like droplet spread, infection occurs when virus-laden aerosols are inhaled or make direct contact with mucous membranes.
Vehicles and Vectors
Vehicles refer to nonliving substances that can harbor virions or bacteria and indirectly spread disease. Some examples include contaminated surfaces (fomites), water, blood, and food. Vectors are living intermediaries that
transmit bacteria or viruses. Bloodsucking insects, especially mosquitoes, ticks, and fleas, are some of the most common vectors and are responsible for the spread of the Zika virus, Lyme disease, and bubonic plague, respectively.
transmit bacteria or viruses. Bloodsucking insects, especially mosquitoes, ticks, and fleas, are some of the most common vectors and are responsible for the spread of the Zika virus, Lyme disease, and bubonic plague, respectively.
Portals
Portals refer to the point of entry and point of exit of a virus. They include the skin, the respiratory tract, the gastrointestinal tract, the genital tract, or through fluids like blood.
Portal of Exit
The portal of exit is the means through which a pathogen leaves a reservoir or host. The release of infectious virions from a host is known as the shedding of virus, and viruses are typically shed from the site of infection. Consequently, skin infections are spread by skin-to-skin contact; respiratory infections are shed via droplets or aerosols released through secretions that escape through the nose and mouth; and gastrointestinal viruses are shed when the host either vomits or has diarrhea, which allows the virus to be conveyed via aerosols or vehicles to a new host. If multiple types of tissues have been infected, then shedding can occur from multiple sites.17
Portal of Entry
Once a virus has been shed, it must then find a new and susceptible host. To infect this host, it must first pass through a portal of entry, oftentimes by exploiting a vulnerability in the host’s epithelium—the protective layer of cells that line an organism’s outer surface (its skin) and internal surfaces, including the respiratory tract, gastrointestinal (GI) tract, and genital tract. Natural defenses exist to prevent infection. The skin is made of a shield of dead cells that viruses cannot penetrate. The internal surfaces of the body—the GI tract, genital tract, and respiratory tract—are coated with a layer of mucus that traps pathogens and prevents them from reaching the epithelium below.
Viral transmission may also occur following the direct penetration of the skin due to an animal or insect bite, transplantation of a virally infected organ, or via placenta between mother and fetus.
Skin
The skin is composed of two layers of tissue: the epidermis and the dermis. The outer layer, the epidermis, is constantly being replaced by a new supply of cells from the inner layer, the dermis. As skin cells rise from the dermis layer, they become saturated with keratin filaments that are produced within the cell. Keratins are found in all vertebrates and form not just the
outer layer of our skin but also our nails and hair. In other animals, keratins form horns, claws, and hooves for other animals.
outer layer of our skin but also our nails and hair. In other animals, keratins form horns, claws, and hooves for other animals.
As the cell keratinizes, it dies via programmed cell death (known as apoptosis) before reaching the epidermis, and then forms the outermost layer of the epidermis, which is known as the stratum corneum. This process, known as cornification, creates a physical barrier of dead cells (corneocytes) that pathogens cannot penetrate. As this layer of cells is no longer alive, viruses cannot use the intercellular mechanisms to replicate. However, viruses can gain entry to lower strata of the epidermis and dermis through abrasions or cuts, or they can be transported from the skin to a more permeable portal of entry, such as one’s eyes, nose, or mouth.
Respiratory Tract
The respiratory tract includes the mouth, nose, throat, and lungs. Like other internal surfaces in the body, the respiratory epithelium is protected by a layer of mucus that traps pathogens, dust, and debris. Small structures known as cilia, which look like tiny hairs, then move in a sweeping motion to carry the debris-laden mucus away. Plentiful in the upper respiratory tract (nasal cavities, sinuses, pharynx, and larynx), cilia and mucus become increasingly less abundant as one moves deeper into the lower respiratory tract (trachea, bronchi, and, finally, the lungs). Pathogens that make it this deep into the respiratory tract and into the lungs are intercepted primarily by immune cells known as alveolar macrophages. Like sentries, they roam around the lungs looking for substances and pathogens that should not be there and eliminate them. They make up 95% of the white blood cells (leukocytes) that occupy airspace in the lungs.18
GI Tract
Much of the epithelia of the GI tract is also coated in a layer of mucus, including the mouth, esophagus, and stomach. Mucus in the latter protects the organ’s lining from both pathogens and the acids produced to aid with digestion. The contents of the stomach then enter the small intestine for additional digestion and the absorption of nutrients through fingerlike projections known as villi, which are coated in membrane protrusions known as microvilli. These structures look like the teeth of a comb.
Villi and microvilli significantly increase the surface area of the intestinal epithelia to allow for more nutrient absorption, but they are also a potential liability because of increased exposure to potential viral or bacterial infections. To offer extra protection beyond mucus, the intestines possess a sophisticated defense network that relies on a healthy biota teeming with microbial life and an innate immune response system housed in the intestinal epithelia.19 The large intestine and colon lack villi and microvilli but are home to a similar defense network of microorganisms and immune system cells.
Genital Tract
Viruses that are transmitted through the genital tract come almost solely from sexual activity. In addition to the mucosal lining of the male genital tract and the female genital tract, each system is home to a microenvironment that is regulated by microorganisms, sex hormones, and innate immune system defenses.20
Phases of Infection
From the time the pathogen invades the host, it rapidly multiplies and simultaneously the body’s immune system mounts a defense to eliminate the infection (see Figure 2.3). In some cases, the body’s immune system may clear the infection quickly enough so that the individual never experiences symptoms. The time period from the point of exposure to the onset of disease symptoms is known as the incubation period. Following this is the prodromal period, which is when early, nonspecific signs and symptoms emerge and before the major symptoms begin to affect the host. Some examples include flulike symptoms such as fatigue, muscle aches, fever, or congestion. Afterward is the illness period, which is when symptoms that are more specific to the disease present themselves. Usually, at this point, the immune system is highly active and mounts a defensive response to
decrease the viral load. Subsequently, the infection subsides and the host begins to feel better. This is known as the convalescent period. The length of each period is dependent on the virus.
decrease the viral load. Subsequently, the infection subsides and the host begins to feel better. This is known as the convalescent period. The length of each period is dependent on the virus.
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