Addendum 19 April 2021
Airborne transmission of SARS-CoV-2
Greenhalgh T, Jimenez JL, Prather KA, Tufekci Z, Fisman D, Schooley R. Ten scientific reasons in support of airborne transmission of SARS-CoV-2. Lancet. 2021 Apr 15:S0140-6736(21)00869-2. PubMed: https://pubmed.gov/33865497. Full-text: https://doi.org/10.1016/S0140-6736(21)00869-2
Allen JG, Ibrahim AM. Indoor Air Changes and Potential Implications for SARS-CoV-2 Transmission. JAMA. 2021 Apr 16. PubMed: https://pubmed.gov/33861316. Full-text: https://doi.org/10.1001/jama.2021.5053
Bazant MZ, Bush JWM. A guideline to limit indoor airborne transmission of COVID-19. Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):e2018995118. PubMed: https://pubmed.gov/33858987. Full-text: https://doi.org/10.1073/pnas.2018995118
CDC 20210405. Science Brief: SARS-CoV-2 and Surface (Fomite) Transmission for Indoor Community Environments. Centers for Disease Control (CDC) 2021, published 5 April (accessed 19 April). Full text: https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/surface-transmission.html
The principal mode by which people are infected with SARS-CoV-2 (the virus that causes COVID-19) is through exposure to respiratory droplets carrying infectious virus. It is possible for people to be infected through contact with contaminated surfaces or objects (fomites), but the risk is generally considered to be low.
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Last revision: 15 December
- Respiratory transmission is the dominant mode of transmission.
- Vertical transmission occurs rarely; transplacental transmission has been documented.
- Direct contact and transmission through fomites (inanimate objects) are presumed but are likely only an unusual mode of transmission.
- Although live virus has been isolated from saliva and stool and viral RNA has been isolated from semen and blood donations, there are no reported cases of SARS-CoV-2 transmission via fecal–oral, sexual, or bloodborne routes. To date, there is one cluster of possible fecal–respiratory transmission.
- Cats and ferrets can be infected and transmit to each other, but there are no reported cases to date of transmission to humans; minks transmit to each other and to humans.
For everyday life, the following five rules of thumb are helpful:
- Avoid crowded places (more than 5-10 people). The more people are grouped together, the higher the probability that a superspreader (see page 84) is present who emits infectious particles tens or hundreds times more than a ‘normally’ contagious individual.
- Avoid in particular crowded and closed spaces (the worst: air-conditioned closed places where ‘old air’ is being moved around). In a room where a SARS-CoV-2 infected individual is coughing frequently, viable virus can be isolated from samples collected 2 to 4,8 meters away.
- Avoid in all circumstances crowded, closed and noisy spaces where people must shout to communicate. Noise from machines or music in a closed environment creates the perfect setting for a superspreader event.
- Outside crowded, closed or noisy spaces, keep a distance of 2 meters to other people.
- Always wear a fask mask in public spaces.
Viruses have substantially influenced human health, interactions with the ecosphere, and societal history and structures (Chappell 2019). In a highly connected world, microbial evolution is boosted and pathogens exploit human behaviors to their own benefit (Morens 2013). This was critically shown during the SARS epidemic in 2003 (Kamps-Hoffmann 2003), the outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) (Zaki 2012), the last great Ebola epidemic in West Africa (Arwady 2015, Heymann 2015) and the Zika epidemic in 2015-2017 (Fauci 2016). Over the same time period, more virulent strains of known respiratory pathogens – H5N1 influenza virus, tuberculosis, avian H7N9 influenza virus – have emerged (Kamps-Hoffmann 2006, Jassal 2009, Gao 2013).
SARS-CoV-2, Severe Acute Respiratory Syndrome coronavirus 2, is a highly transmissible ‘complex killer’ (Cyranoski 2020) that forced half of humanity, 4 billion people, to bunker down in their homes in the early spring of 2020. The respiratory disease rapidly evolved into a pandemic (Google 2020). In most cases, the illness is asymptomatic or paucisymptomatic and self-limited. A subset of infected individuals has severe symptoms and sometimes prolonged courses (Garner 2020). Around 10% of infected people need hospitalization and around one third of them treatment in intensive care units. The overall mortality rate of SARS-CoV-2 infection seems to be less than 1%.
Coronaviruses are tiny spheres of about 70 to 80 nanometers (a millionth of a millimeter) on thin-section electron microscopy (Perlman 2019). Compared to the size of a human, SARS-CoV-2 is as small as a big chicken compared to the planet Earth (El País). The raison d’être of SARS-CoV-2 is to proliferate, like that of other species, for example H. sapiens sapiens who has been successful in populating almost every corner of the world, sometimes at the expense of other species. SARS-CoV-2, for now, seems to be on a similarly successful track. By 7 June, only a handful of countries can claim to have been spared by the pandemic.
SARS-CoV-2’s global success has multiple reasons. The new coronavirus hijacks the human respiratory system to pass from one individual to another when people sneeze, cough, shout and speak. It is at ease both in cold and in warm climates; and, most importantly and unlike the two other deadly coronaviruses SARS-CoV and MERS-CoV, it manages to get transmitted to the next individual before it develops symptoms in the first one (see below, Asymptomatic Infection, page 85). There is no doubt that SARS-CoV-2 has a bright future – at least until the scientific community develops a safe vaccine (see the chapter Vaccines, page 173) and efficient drugs.
COVID Reference resources:
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SARS-CoV-2 and its kin
SARS-CoV-2 is a coronavirus like
- SARS-CoV (cousin from the 2002/2003 epidemic),
- MERS-CoV (Middle East Respiratory Syndrome coronavirus),
- and a group of so-called CAR coronoviruses (for Community-Acquired Respiratory CoVs: 229E, OC43, NL63, HKU1).
The CAR group of viruses are highly transmissible and produce about 15 to 30% of common colds, typically in the winter months. On the contrary, SARS-CoV and MERS-CoV have case fatality rates of 10% and 34%, respectively, but they never achieved pandemic spread. SARS-CoV-2, from a strictly viral point of view, is the shooting star in the coronavirus family: it combines high transmissibility with high morbidity and mortality.
SARS-CoV-2 is a virus like other commonly known viruses that cause human disease such as hepatitis C, hepatitic B, Ebola, influenza and human immunodeficiency viruses. (Note that the differences between them are bigger than those between humans and amebas.) With the exception of influenza, these viruses have a harder time infecting humans than SARS-CoV-2. Hepatitis C virus (HCV), a major cause of chronic and often fatal liver disease, is mainly transmitted by percutaneous exposure to blood, by unsafe medical practices and, less frequently, sexually. The human immunodeficiency virus (HIV), in addition to exposure to blood and perinatal transmission, also exploits sexual contact as a potent transmission route. Hepatitis B virus (HBV) is an even more versatile spreader than HCV and HIV as it can be found in high titers in blood, cervical secretions, semen, saliva, and tears; even tiny amounts of blood or contaminated secretions can transmit the virus. Ideal infection environments for HBV include, for example, schools, institutions and hospitals where individuals are in close and prolonged contact.
Of note, apart from HIV and hepatitis B and C, most viral diseases have no treatment. For example, there is no treatment for measles, polio, or smallpox. For influenza, decades of research have produced two specific drugs which have not been able to demonstrate reduced mortality – despite tests on thousands of patients. After 35 years of research, there is still no vaccine to prevent HIV infection.
SARS-CoV-2 is present at the highest concentrations in the respiratory tract early in disease and then increases in the lower respiratory tract (Zhu N 2020, Wang 2020, Huang 2020, Wölfel 2020). The virus has also been found, albeit at low levels, in the kidney, liver, heart, brain, and blood (Puelles 2020). Outside the human body, the virus is more stable at low temperature and low humidity conditions, whereas warmer temperatures and higher humidity shorten the half-life (Matson 2020). It has also been shown to be detectable as an aerosol (in the air) for up to three hours, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel (van Doremalen 2020). As expected, viral RNA was more likely to be found in areas immediately occupied by COVID-19 patients than in other hospital areas (Zhou J 2020). Another study documented contamination of toilets (toilet bowl, sink, and door handle) and air outlet fans (Ong SWX 2020). This is in line with the experience from MERS where many environmental surfaces of patients’ rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV (Bin 2016).
Person-to-person transmission of SARS-CoV-2 was established within weeks of identification of the first cases (Chan JF 2020, Rothe 2020). Shortly after, it was suggested that asymptomatic individuals would probably account for a substantial proportion of all SARS-CoV-2 transmissions (Nishiura 2020, Li 2020). Viral load can be high 2-3 days before the onset of symptoms and almost half of all secondary infections are supposed to be caused by pre-symptomatic patients (He 2020).
A key factor in the transmissibility of SARS-CoV-2 is the high level of viral shedding in the upper respiratory tract (Wolfel 2020), even among paucisymptomatic patients. Pharyngeal virus shedding is very high during the first week of symptoms, with a peak at > 7 x 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung. That distinguishes it from SARS-CoV, where replication occured mainly in the lower respiratory tract (Gandhi 2020); SARS-CoV and MERS-CoV infect intrapulmonary epithelial cells more than cells of the upper airways (Cheng PK 2004, Hui 2018).
The shedding of viral RNA from sputum appears to outlast the end of symptoms and seroconversion is not always followed by a rapid decline in viral load (Wolfel 2020). This contrasts with influenza where persons with asymptomatic disease generally have lower quantitative viral loads in secretions from the upper respiratory tract than from the lower respiratory tract and a shorter duration of viral shedding than persons with symptoms (Ip 2017).
A recently published review summarized the evidence of human SARS-CoV-2 transmission (Meyerowitz 2020):
- Respiratory transmission is the dominant mode of transmission.
- Vertical transmission occurs rarely; transplacental transmission has been documented.
- Direct contact and fomite transmission are presumed but are likely only an unusual mode of transmission.
- Although live virus has been isolated from saliva and stool and viral RNA has been isolated from semen and blood donations, there are no reported cases of SARS-CoV-2 transmission via fecal–oral, sexual, or bloodborne routes. To date, there is 1 cluster of possible fecal–respiratory transmission.
- Cats and ferrets can be infected and transmit to each other, but there are no reported cases to date of transmission to humans; minks transmit to each other and to humans.
SARS-CoV-2 is spread predominantly via virus-containing droplets through sneezing, coughing, or when people interact with each other for some time in close proximity (usually less than one metre) (ECDC 2020, Chan JF 2020, Li Q 2020, Liu Y 2020, Lu J 2020). Direct contact or fomite transmission is suspected and may occur in some cases. Sexual, fecal–oral, and bloodborne transmission are theorized but have not been documented (Meyerowitz 2020).
The upper respiratory tract is the usual initial site of viral replication, with subsequent descending infection (Wölfel 2020). The ideal transmission setting for SARS-CoV-2 is a crowded, closed and noisy space where people must shout to communicate. Shouting or speaking loudly emits a continuous flow of large droplets or fine aerosols laden with virions. Although aerosol lingers in the air for minutes, capable of infecting people at a distance, the ideal transmission setting (the ‘SARS-CoV-2 jackpot’ from the virus’s point of view) are people shouting at one another at a short distance, inhaling deep into theirs lungs the exhalations of the person they are speaking to/shouting at for 5, 10, 20 minutes or longer. Noisy machines, loud music or high spirits during exuberant gatherings in crowded and closed environments are therefore the perfect conditions for exceptionally efficient SARS-CoV-2 transmission.
Figure 1. Transmission of SARS-CoV-2. 1) After coughing, sneezing, shouting and even after speaking – particularly loud speaking–, large droplets (green) drop to the ground around the young man. 2) In addition, some droplets, small and lightweight enough (red), are transported by air currents over longer distances (WHO 20200709). The second – aerosol – transmission is now recognized as a possibly relevant transmission route in SARS-CoV-2. Adapted from Morawska 2020. Art work: Félix Prudhomme – IYENSS.
SARS-CoV-2 is transmitted via (macro-)droplets greater than 5-10 μm in diameter, commonly referred to as respiratory droplets, and via smaller particles, < 5μm in diameter, which are referred to as droplet nuclei or aerosols. The almost century-old dichotomy (Wells 1934) “droplets vs. aerosol transmission” has been challenged by SARS-CoV-2. It is now accepted that there is no real evidence that SARS-CoV-2 pathogens should be carried only in large droplets (Fennelly 2020). At the beginning of the pandemic, aerosol transmission of SARS-CoV-2 was generally not accepted; however, within months, it became evident that some COVID-19 clusters, for example in choirs (Hamner 2020, Miller 2020), shopping malls (Cai J 2020), restaurants (Li Y 2020 + Lu J 2020), meat processing plants (Günter 2020, The Guardian) or vertically aligned flats connected by drainage pipes in the master bathrooms (Kang M 2020, Gormley 2020), were best explained by aerosol transmission (Ma J 2020).
On July 9 2020, WHO updated its information about SARS-CoV-2 transmission (WHO 20200709), “There have been reported outbreaks of COVID-19 in some closed settings, such as restaurants, nightclubs, places of worship or places of work where people may be shouting, talking, or singing. In these outbreaks, aerosol transmission, particularly in these indoor locations where there are crowded and inadequately ventilated spaces where infected persons spend long periods of time with others, cannot be ruled out.” In the preceding days, a group of more than 200 scientists led by Lidia Morawska and Donald K. Milton had published a three-page warning: It is Time to Address Airborne Transmission of COVID-19 (see also LM’s first alert on 10 April and the overviews by Prather, Wang and Schooley as well as Jayaweera 2020 et al.).
A single cough from a person with a high viral load in respiratory fluid (2,35 × 109 copies per ml) may generate as many as 1,23 × 105 copies of viruses that can remain airborne after 10 seconds, compared to 386 copies of a normal patient (7,00 × 106 copies per ml) (Wang Y 2020). (And masking can block around 94% of the viruses that may otherwise remain airborne after 10 seconds). A recent demonstration of aerosol production visualizes speech-generated oral fluid droplets and underlines that even normal speaking may be an important mode of transmission (Bax 2020). The authors provide videos showing speech droplets emitted by four people, when speaking the phrase “spit happens” with the face positioned about 10–15 cm behind a thin sheet of intense green laser light (video: https://www.youtube.com/watch?v=ooVjNth4ut8). Previously, experimental support for aerosol transmission of SARS-CoV-2 came from studies that visualized droplet formation at the exit of the mouth during violent expiratory events such as sneezing and coughing (Scharfman 2016, Bourouiba 2020; see also the video). These studies showed that the lifetime of a droplet could be considerably longer than previously assumed. When analyzed with highly sensitive laser light scattering, loud speech was found to be able to emit thousands of oral fluid droplets per second which could linger in the air for minutes (Anfinrud 2020, Stadnytskyi 2020; see also the movies showing the experimental setup and the critical comment by Abbas 2020). Loud and persistent shouting as would be usual in noisy, closed and stagnant air environments (meat packing facilities, discos, pubs, etc.) is now believed to produce the same number of droplets as produced by coughing (Chao 2020). Speech and other vocal activities such as singing have also been shown to generate air particles, with the rate of emission corresponding to voice loudness (Asadi 2019).
Of note, during the 2003 SARS epidemic, an airborne route of transmission also appeared to be a plausible explanation for the so-called Amoy Garden outbreak. On that occasion, the virus was aerosolized within the confines of very small bathrooms and may have been inhaled, ingested or transmitted indirectly by contact with fomites as the aerosol settled (WHO 2003).
Morawska, Milton et al. suggested the following measures to mitigate airborne transmission of SARS-CoV-2:
- Provide sufficient and effective ventilation (supply clean outdoor air, minimize recirculating air) particularly in public buildings, workplace environments, schools, hospitals, and retirement care homes
Infrastructure may have to be adjusted, for example, Heating, Ventilation and Air Conditioning Systems (HVAC) in buildings and on ships (Correia 2020, Gormley 2020). In one study, viral RNA was detected in ventilation exhaust filters located at least 50 m from patient room vent openings (Nissen 2020).
- Supplement general ventilation with airborne infection controls such as local exhaust, high efficiency air filtration, and germicidal ultraviolet lights.
- Avoid overcrowding, particularly in public transport and public buildings.
A precautionary approach to COVID-19 prevention is shown in Table 1.
|Table 1. Reducing the transmission of SARS-CoV-2|
|1. (Macro-)Droplets (> 5 µm)||Face masks + social distancing|
|2. Aerosol (micro-droplets, ≤ 5µm)||· Face masks
· Improved ventilation
· Improved air filtering
· Avoidance of crowded and closed spaces
For mechanical systems, organizations such as ASHRAE (the American Society of Heating, Ventilating, and Air Conditioning Engineers) and REHVA (the Federation of European Heating, Ventilation and Air Conditioning Associations) have provided guidelines based on the existing evidence of airborne transmission (Morawska 2020b).
The evidence for aerosol transmission and resulting recommendations for prevention have been sublimely summarized by Prather et al. in five sentences: “Respiratory infections occur through the transmission of virus-containing droplets (>5 to 10 μm) and aerosols (≤5 μm) exhaled from infected individuals during breathing, speaking, coughing, and sneezing. Traditional respiratory disease control measures are designed to reduce transmission by droplets produced in the sneezes and coughs of infected individuals. However, a large proportion of the spread of coronavirus disease 2019 (COVID-19) appears to be occurring through airborne transmission of aerosols produced by asymptomatic individuals during breathing and speaking (Morawska 2020, Anderson 2020, Asadi 2019). Aerosols can accumulate, remain infectious in indoor air for hours, and be easily inhaled deep into the lungs. For society to resume, measures designed to reduce aerosol transmission must be implemented, including universal masking and regular, widespread testing to identify and isolate infected asymptomatic individuals (Prather 2020).”
Recognizing that SARS-CoV-2 is transmitted via aerosol has far-reaching consequences – personal, professional, societal and economic – in situations of community COVID-19 outbreaks. At the personal level (reminder: 20% of infected individuals are thought to transmit 80% of SARS-CoV-2 cases, so minimizing the probability of coming close to such super-spreader invidivuals is imperative), people might wish to avoid prolonged meetings with people from outside their inner-core “friends-and-family-bubble”; inside the bubble, meetings should be restricted to a handful of people.
At the professional level, healthcare workers will require nothing short of optimal protection. As N95 respirators achieve better filtration of airborne particles than medical masks, they should be recommended for all inpatient care of patients with COVID-19, not only during aerosol generating procedures (Dau 2020). Guideline recommendations that do not support N95 use for all inpatient COVID-19 management should consider reevaluating the existing data.
At the societal level, the attendance of important biographic events such as weddings, baptisms, circumcisions and funerals may need to be limited to a handful of intimate friends and family (probably less than 10). Religious services and recreational activities such as team sport and choir singing may not be possible.
At the economic level, all activities which bring numerous people from outside the “friends-and-family-bubbles” together may be banned during new community outbreaks. Future curfews or lockdowns would target places where strangers or simply unacquainted people meet: discos, amusement parks, bars, restaurants, brothels and many more. Other activities such as meat processing plants might need major restructuring before resuming work. Foreigners, strangers or simply unacquainted people may not meet for some time. SARS-CoV-2 will thus continue to impact cultural and economic life – theaters, cinemas, bars, restaurants, shops, etc – for some time to come.
In the meantime, the discussion about SARS-CoV-2 and aerosols continues. Even the droplet/aerosol terminology has recently been questioned by advocates of a new distinction between aerosols and droplets using a size threshold of 100 μm, not the historical 5 μm (Prather 2020). The authors argue that this size more effectively separates their aerodynamic behavior, ability to be inhaled, and efficacy of interventions. Viruses in droplets (larger than 100 μm) typically fall to the ground in seconds within 2 m of the source and can be sprayed like tiny cannonballs onto nearby individuals. Recently, a fourth transmission route has been hypothesized: aerosolized fomites. In this case, virus would remain viable in the environment, on materials like paper tissues and on the bodies of living animals, long enough to be aerosolized on non-respiratory dust particles that can transmit infection through the air to new mammalian hosts (Asadi 2020). In retrospective, we will one day understand that transmission of viruses is not the only conceptual framework upset by the SARS-CoV-2 virus.
At the beginning of the SARS-CoV-2 pandemic, it was unclear to what extent transmission via fomites (e.g., elevator buttons, hand rails, restroom taps) were epidemiologically relevant. [A fomite is any inanimate object that, when contaminated with or exposed to infectious agents such as a virus, can transfer a disease to another person.] SARS-CoV-2 seemed omnipresent in the spaces inhabited by infected individuals where a protein-rich medium like airway secretions could protect the virus when it was expelled and could enhance its persistence and transmission by contaminated fomites (Pastorino 2020). The transmission sequence included virus-laden droplets from SARS-CoV-2 infected people land on surfaces; there the virus would be detectable for up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel (van Doremalen 2020, Aboubakr 2020, Joonaki 2020); and finally, other people coming into contact with these droplets, touching their nose, mouth or eyes (Wang Y 2020, Deng W 2020) and getting infected. Some studies reported that SARS-CoV-2 environmental contamination around COVID-19 patients was extensive, and hospital infection prevention and control procedures should account for the risk of fomite, and potentially airborne, transmission of the virus (Santarpia 2020). On a cruise ship, SARS-CoV-2 RNA was detected in 10% from cabins 1-17 days after SARS-CoV-2 infected individuals left their cabins (Yamagishi 2020). Find an overview of studies assessing viral RNA on surfaces and in air samples in Meyerowitz 2020, Table 1.
However, in real-world settings, SARS-CoV-2 RNA levels are markedly lower on environmental surfaces than in the human nasopharynx (Lui G 2020, Jiang FC 2020) and in the rare cases where fomite transmission has been discussed, respiratory transmission could not be excluded (Cai J 2020, Bae SH 2020). Some authors now question the role of fomites in SARS-CoV-2 transmission and suggest that the chance transmission through inanimate surfaces might be less frequent than hitherto assumed (Mondelli 2020) and less likely to occur in real-life conditions, provided that standard cleaning procedures and precautions are enforced. Transmission through fomites would occur only in instances where an infected person coughs or sneezes on the surface, and someone else touches that surface soon after the cough or sneeze (within 1–2 h) (Goldman 2020). Another group estimated risk of infection from touching a contaminated surface at less than 5 in 10.000 after repeatedly sampling 33 surfaces in public places like liquor and grocery stores, banks, gas stations, laundromats, restaurants and on metro doors and crosswalk buttons (Harvey 2020). Twenty-nine of 348 (8.3 %) surface samples were positive for SARS-CoV-2. These authors suggest that fomites might play only a minimal role in SARS-CoV-2 community transmission.
In conclusion, direct contact and fomite transmission are likely to be only an unusual mode of transmission and on the basis of currently available data, we should assume that the levels of viral RNA or live virus transiently remaining on surfaces are unlikely to cause infection, especially outside of settings with known active cases (Meyerowitz 2020). It is important to stress that this finding should not persuade anyone to refrain from the ritual of regular and thorough handwashing; however, it could calm fears of people who are anxious about touching things in everyday life (doorknobs, keys, money, smartphones, etc.).
Vertical transmission occurs rarely. SARS-CoV-2 IgM has been reported in neonates (Zeng H 2020, Dong L 2020) but there is no consensus on the interpretation of this finding (Kimberlin 2020). Although SARS-CoV-2 was detected in breast milk (Groß 2020), no confirmed transmissions to infants from breast milk have been reported (Marín Gabriel 2020, Chambers 2020). Find more information in the chapter Pediatrics, page 382.
SARS-CoV-2 can infect domestic animals, including cats, dogs, and ferrets (Shi J 2020, Richard 2020, Garigliany 2020). SARS-CoV-2 has been transmitted from their owners to cats and dogs (Newman 2020, Garigliany 2020) but there is currently no evidence of transmission from domestic pets to humans. When inoculated with SARS-CoV-2, cats could transmit the virus to other cats (Halfmann 2020) and although none of the cats showed symptoms, all shed virus for 4 to 5 days and developed antibody titers by day 24. In another report, two out of fifteen dogs from households with confirmed human cases of COVID-19 in Hong Kong were found to be infected. The genetic sequences of viruses from the two dogs were identical to the virus detected in the respective human cases (Sit 2020). In still another paper, 919 companion animals in northern Italy at the height of the spring 2020 epidemic were tested for SARS-CoV-2. Although no animals tested PCR positive, 3.3% of dogs and 5.8% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households (Patterson 2020).
Evidence of infection of animals with SARS-CoV-2 has been shown experimentally both in vivo and in vitro for monkeys, ferrets, rabbits, foxes, and hamsters (Edwards 2020). While computational models also predicted infectivity of pigs and wild boar (Santini 2020), a recent study suggested that pigs and chickens could not be infected intranasally or oculo-oronasally by SARS-CoV-2 (Schlottau 2020).
At present, it seems unlikely that animals are potential intermediate hosts in the chain of human–pet–human transmission. Only special circumstances, such as the high animal population densities encountered on mink farms, might put humans at risk of animal-to-human transmission (Oreshkova 2020).
Persons with COVID-19 should be advised to avoid contact with animals. Companion animals that test positive for SARS-CoV-2 should be monitored and separated from persons and other animals until they recover (Newman 2020).
Hypothetical modes of transmission
Live virus can rarely be isolated from stool and saliva and SARS-CoV-2 RNA has been isolated from semen and blood donations; however, in early December 2020, there were no reported cases of SARS-CoV-2 transmission via fecal–oral, sexual, or bloodborne routes.
There is currently no evidence for relevant fecal–oral SARS-CoV-2 transmission. Although a high concentration of ACE2 receptors in the small bowel (Gu J 2020) and prolonged presence of SARS-CoV-2 viral RNA in fecal samples have been reported (Wu Y 2020, Chen 2020, Du W 2020), live virus has only rarely been detected in stool (Wang W 2020, van Doorn 2020, Sun J 2020, Parasa 2020). This finding should not interfere with the usual precautions when handling the stools of patients infected with coronavirus. Sewage from hospitals should also be properly disinfected (Yeo 2020). Fortunately, antiseptics and disinfectants such as ethanol or bleach have good activity on human coronaviruses (Geller 2012). During the SARS-CoV outbreak in 2003, where SARS-CoV was shown to survive in sewage for 14 days at 4°C and for 2 days at 20°C (Wang XW 2005), environmental conditions could have facilitated this route of transmission.
Recently, immunofluorescence and immunohistochemical analyses detected SARS-CoV-2 spike proteins in three of five patients. In these cases, the virus resided primarily in the sweat glands and sweat ducts with apparently higher amounts in the former than in the latter; in contrast, the virus was rarely detected in the epidermis or sebaceous glands (Liu J 2020). The authors concluded that it was “important to further assess the potential risk of viral transmission via perspiration and skin contact.” (Editor’s note: This paper will not change my standard protection measures.)
SARS-CoV-2 is rarely detected in blood (Wang W 2020, Wolfel 2020). After screening of 2430 donations in real-time (1656 platelet and 774 whole blood), authors from Wuhan found plasma samples positive for viral RNA from 4 asymptomatic donors (Chang 2020). In a Korean study, seven asymptomatic blood donors were later identified as COVID-19 cases. None of 9 recipients of platelets or red blood cell transfusions tested positive for SARS-CoV-2 RNA (Kwon 2020). In early December 2020, there was no evidence of replication-competent virus isolated from blood samples and no documented case of bloodborne transmission.
It is unknown whether purely sexual transmission is possible. Scrupulously eluding infection via fomites and respiratory droplets during sexual intercourse would suppose remarkable acrobatics many people might not be willing to perform. Reassuringly, SARS-CoV-2 doesn’t seem to be present in semen (Guo L 2020). Studies published until today showed viral RNA, but no infectious virus in semen (Li 2020) and viral RNA in vaginal fluid on only one occasion (Scorzolini 2020, Qiu L 2020). In a small study from Orléans, France, there was no transmission among discordant partners among five couples who continued sex while one partner was in the period of infectiousness (Prazuck 2020).
Transmission of a virus from one person to another depends on four variables:
- The nature of the virus;
- The nature of the transmitter;
- The nature of the transmittee (the person who will become infected);
- The transmission setting.
In order to stay in the evolutionary game, all viruses have to overcome a series of challenges. They must attach to cells; fuse with their membranes; release their nucleic acid into the cell; manage to make copies of themselves; and have the copies exit the cell to infect other cells. In addition, respiratory viruses must make their host cough and sneeze to get back into the environment again. Ideally, this happens before the hosts realize that they are sick. This is all the more amazing as SARS-CoV-2 is more like a piece of computer code than a living creature in sensu strictu (its 30,000 DNA base pairs are a mere 100,000th of the human genetic code). That doesn’t prevent the virus from being ferociously successful:
- It attaches to the human angiotensin converting enzyme 2 (ACE2) receptor (Zhou 2020) which is present not only in nasopharyngeal and oropharyngeal mucosa, but also in lung cells, such as in type II pneumocytes. SARS-CoV-2 thus combines the high transmission rates of the common coronavirus NL63 (infection of the upper respiratory tract) with the severity of SARS in 2003 (lower respiratory tract);
- It has a relatively long incubation time of around 5 days (influenza: 1-2 days), thus giving it more time to spread;
- It is transmitted by asymptomatic individuals.
All viruses mutate. Mutations within coronaviruses, and indeed all RNA viruses, can arrive as a result of three processes. First, mutations arise intrinsically as copying errors during viral replication, a process which may be reduced in SARS-CoV-2 relative to other RNA viruses, due to the fact that coronavirus polymerases include a proof-reading mechanism (van Dorp 2020). Second, genomic variability might arise as the result of recombination between two viral lineages co-infecting the same host. Third, mutations can be induced by host RNA-editing systems, which form part of natural host immunity. Based on epidemiological data, a SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has been associated with increased infectivity (Korber 2020). In one study, the D614G also exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection (Hou YJ 2020). However, after analyzing 46.723 SARS-CoV-2 genomes isolated from patients worldwide, one group could not identify a single recurrent mutation which was convincingly associated with increased viral transmission. The debate on the significance of the D614G mutation goes on (van Dorp 2020).
The mean incubation of SARS-CoV-2 infection is around 5 days (Lauer 2020, Li 2020, Zhang J 2020, Pung 2020), comparable to that of the coronaviruses causing SARS or MERS (Virlogeux 2016). Almost all symptomatic individuals will develop symptoms within 14 days of infection (Bai Y 2020). Both symptomatic and asymptomatic individuals can transmit SARS-CoV-2 (Bai Y 2020, Qian G 2020, Chau NVV 2020, Luo L 2020). About half of secondary cases are acquired from persons who are presymptomatic at the time of transmission (Shresta 2020, Yang L 2020, Xu XK 2020). Viral shedding may not be distinguishable between symptomatic and asymptomatic individuals (Lee S 2020, Long QX 2020).
Infectiousness, measured by the detection of cultivatable virus, seems to start around two days before symptom onset, peaks around a day before symptom onset, and declines rapidly within a week (He X 2020, Lauer 2020). It is still unknown how many days infected people can transmit the virus, although some authors suggest that the infectivity window might be as short as one day (Goyal 2020) as SARS-CoV-2 viral load in the respiratory tract rapidly decreases after symptom onset (Wölfel 2020, Guo L 2020, To KK 2020). The duration of SARS-CoV-2 RNA shedding may go on for weeks and sometimes for months (Sun J 2020); however, multiple studies have found virtually no viable virus in patients with mild or moderate disease after 10 days of symptoms despite frequent ongoing RNA shedding (Wölfel 2020, Singanayagam 2020, Perera 2020). Ten days after symptom onset, the probability of culturing virus declined to 6.0% (Singanayagam 2020). In other studies, no viable virus was detected beyond 8 or 9 days after symptom onset and with SARS-CoV-2 RT-PCR cycle threshold (Ct) values > 24 (Bullard 2020, Arons 2020). In a study from Taiwan, there was zero transmission to 852 contacts who were exposed to the index case after day 6 of symptom onset (Cheng HY 2020). Requiring a negative RNA test as late as 21 days after the onset of symptoms to declare the end of quarantine as practised has no scientific basis.
The minimum human infectious dose is unknown. A phylogenetic-epidemiological model estimated the number of virions needed to start an infection at around 101-103 (Popa 2020).
Symptom severity of the index may have an impact on transmission probability. In one study of 3410 close contacts of 391 SARS-CoV-2 infected index cases, the secondary attack rate increased with the severity of index cases, from 0.3% for asymptomatic to 3,3% for mild, 5,6% for moderate, and 6,2% for severe or critical cases (Luo L 2020). Fever and expectoration were associated with an increased risk for infection in their close contacts (6,7% and 13,6%, respectively). SARS-CoV-2 transmission probably correlates with higher viral loads which in turn is associated with more frequent isolation of infectious virus (Singanayagam 2020).
SARS-CoV-2 transmission certainly correlates with a still ill-defined “super-spreader status” of the infected individual. For unknown reasons, some individuals are remarkably contagious, capable of infecting dozens or hundreds of people, possibly because they breathe out many more particles than others when they talk (Asadi 2019), shout, cough or sneeze. Transmission of SARS-CoV and MERS-CoV as well occurred to a large extent by means of super-spreading events (Peiris 2004, Hui 2018). Super-spreading has been recognized for years to be a normal feature of disease spread (Lloyd-Smith 2005). Several groups suggest that 80% of secondary transmissions could be caused by around 10% to 20% of infectious individuals (Bi Q 2020, Adam 2020, Miller 2020, Sun 2020). A value called the dispersion factor (k) describes this phenomenon. The lower the k is, the more transmission comes from a small number of people (Kupferschmidt 2020, Tufekci 2020; if you like the FT, read also To beat Covid-19, find today’s superspreading ‘Typhoid Marys’). While SARS was estimated to have a k of 0.16 (Lloyd-Smith 2005) and MERS of 0.25, in the flu pandemic of 1918, in contrast, the value was about one, indicating that clusters played less of a role (Endo 2020). For the SARS-CoV-2 pandemic, the dispersion factor (k) is currently thought to be higher than for SARS and lower than for the 1918 influenza (Endo 2020, Miller 2020, On Kwok 2020, Wang L 2020). A study of 1407 transmission pairs that formed 643 transmission clusters in mainland China identified 34 super-spreaders, with 29 super-spreading events occurring outside households (Xu XK 2020).
Recently, a mobility network model mapped the hourly movements of 98 million people from neighborhoods to points of interest (POIs) such as restaurants and religious establishments. After connecting 57.000 neighborhoods to 553.000 POIs, the model predicted that a small minority of “superspreader” POIs account for a large majority of infections (Chang S 2020) and that restricting maximum occupancy at each POI (for example, restaurants, gyms, cafes, etc.) (Ma KC 2020, Cyranoski 2020) is more effective than uniformly reducing mobility. [The model also correctly predicted higher infection rates among disadvantaged racial and socioeconomic groups: disadvantaged groups cannot reduce mobility as sharply as other groups and the POIs they visit are more crowded.]
Transmission is more likely when the infected individual has few or no symptoms because while people experiencing symptoms may self-isolate or seek medical care, those with no or mild symptoms may continue to circulate in the community. Asymptomatic individuals have therefore an outsized influence on maintaining the epidemic (Lee EC 2020). Asymptomatic transmission of SARS-CoV-2 – proven a few weeks after the beginning of the pandemic (Bai Y 2020) – has justly been called the Achilles’ heel of the COVID-19 pandemic (Gandhi 2020). As shown during an outbreak in a skilled nursing facility, the percentage of asymptomatic individuals can be as high as 50% early (Arons 2020; most of these individuals would later develop some symptoms). Importantly, SARS-CoV-2 viral load was comparable in individuals with typical and atypical symptoms, and in those who were pre-symptomatic or asymptomatic. Seventeen of 24 specimens (71%) from pre-symptomatic persons had viable virus by culture 1 to 6 days before the development of symptoms (Arons 2020), suggesting that SARS-CoV-2 may be shed at high concentrations before symptom development.
Note that although SARS-CoV-2 is highly transmissible, given the right circumstances and the right prevention precautions, zero transmission is possible. In one case report, there was no evidence of transmission to 16 close contacts, among them 10 high-risk contacts, from a patient with mild illness and positive tests for up to 18 days after diagnosis (Scott 2020).
To what extent children contribute to the spread of SARS-CoV-2 infection in a community is unknown. Infants and young children are normally at high risk for respiratory tract infections. The immaturity of the infant immune system may alter the outcome of viral infection and is thought to contribute to the severe episodes of influenza or respiratory syncytial virus infection in this age group (Tregoning 2010). Until now, however, there is a surprising absence of pediatric patients with COVID-19, something that has perplexed clinicians, epidemiologists, and scientists (Kelvin 2020). In particular, children younger than 10 years seem to be less susceptible than adults (around 50%) (Zhang J 2020, Jing QL 2020, Li W 2020, Gudbjartsson 2020, Davies 2020, Rosenberg 2020).
Although a retrospective study among individuals hospitalized in Milan showed that only about 1% of children and 9% of adults without any symptoms or signs of SARS-CoV-2 infection tested positive for SARS-CoV-2 (Milani 2020) – suggesting a minor role of children in transmission –, children can be the source for important outbreaks. Twelve children who acquired SARS-CoV-2 infection in child-care facilities – all with mild or no symptoms – transmitted the virus to at least 12 (26%) of 46 non-facility contacts (Lopez 2020). Family gatherings are well-known settings for widespread SARS-CoV-2 transmission. In an outbreak that occurred during a 3-week family gathering of five households, an adolescent aged 13 years was the suspected primary patient. Among the 14 persons who stayed in the same house, 12 experienced symptoms (Schwartz 2020). Of note, none of the additional six family members who maintained outdoor physical distance without face masks during two longer visits (10 and 3 hours) to the family gathering developed symptoms.
In any potential transmission setting, face coverings reduce the transmission of SARS-CoV-2. Among 139 clients exposed to two symptomatic hair stylists with confirmed COVID-19 while both the stylists and the clients wore face masks, not a single symptomatic secondary case was observed; among 67 clients tested for SARS-CoV-2, all tests were negative (Hendrix 2020). At least one hair stylist was infectious: all four close household contacts (presumably without masks) became ill. In Germany, face masks may have reduced the daily growth rate of reported infections by around 47% (Mitze 2020). Unfortunately, face masks don’t work everywhere – and not for everyone. In some countries, infected individuals claimed the right to not wear face coverings in the name of liberty (they forgot that an individual’s liberty ends where it infringes on the liberties of others). Interestingly, social distancing compliance might be predicted by individual differences in working memory (WM) capacity. WM retains a limited amount of information over a short period of time at the service of other ongoing mental activities. Limited WM capacity constrains mental functions while extended capacities are often associated with better cognitive and affective outcomes. The hidden message in the paper by Weizhen Xie et al: if the guy sitting next to you in the bus does not wear a mask, don’t insist. His working memory capacity is poor (Xie W 2020). Change seats.
Upon exposure to SARS-CoV-2, the virus may come in contact with cells of the upper or lower respiratory tract of an individual. After inhalation, larger respiratory droplets are filtered by the nose or deposited in the oropharynx, whereas smaller droplet nuclei are carried by the airstream into the lungs where their site of deposition depends on their mass, size and shape and is governed by various mechanisms (Dhand 2020).
A high percentage of SARS-CoV-2 seronegative individuals have SARS-CoV-2 reactive T cells. This is explained by previous exposure to other coronaviruses (“common cold” coronaviruses) which have proteins that are highly similar to those of SARS-CoV-2. It is still unclear whether these cross-reactive T cells confer some degree of protection, are inconsequential or even potentially harmful if someone who possesses these cells becomes infected with SARS-CoV-2 (Braun 2020, Grifoni 2020, Sagar 2020, Meyerholz 2020b).
Numerous cell entry mechanisms of SARS-CoV-2 have been identified that potentially contribute to the immune evasion, cell infectivity, and wide spread of SARS-CoV-2 (Shang J 2020). Susceptibility to SARS-CoV-2 infection is probably influenced by the host genotype. This would explain the higher percentage of severe COVID-19 in men (Bastard 2020, Zhang Q 2020, Piccininni 2020) and possibly the similar disease course in some twins in the UK (The Guardian, 5 May 2020).
The “right” genotype may not be sufficient in the presence of massive exposure, for example by numerous infected people and on multiple occassions as might happen, for example, in health care institutions being overwhelmed during the beginning of an epidemic. It is known from other infectious diseases that viral load can influence the incidence and severity of disease. Although the evidence is limited, high infection rates among health workers have been attributed to more frequent contact with infected patients, and frequent exposure to excretia with high viral load (Little 2020).
Recently, it has been shown that rigorous social distancing not only slowed the spread of SARS-CoV-2 in a cohort of young, healthy adults but also prevented symptomatic COVID-19 while still inducing an immune response (Bielecki 2020). After an outbreak in two Swiss army companies (company 2 and 3, see Table 2), 62% of tested soldiers were found to have been exposed to SARS-CoV-2 and almost 30% had COVID-19 symptoms. In company 1 where strict distancing and hygiene measures (SDHMs) had been implemented after the outbreak in companies 2 and 3, only 15% had exposure to SARS-CoV-2, but none of them had COVID-19 symptoms. (The Swiss army SDHMs: keep a distance of at least 2 m from each other at all times; wear a surgical face mask in situations where this can not be avoided [e.g., military training]; enforce a distance of 2 m between beds and during meals; clear and disinfect all sanitary facilities twice daily; separate symptomatic soldiers immediately.)
|Table 2: Baseline characteristics of the study population on March 31, 2020|
|Company 1||Company 2||Company 3||Company 2+3|
|Exposed to SARS-CoV-2**||13/88 (15%)||83/130 (64%)||30/51 (59%)||113/181 (62%)|
|COVID-19***||0 (0%)||54/200 (27%)||48/154 (31%)||102/354 (29%)|
* More than 50% of the soldiers of all companies were sampled on April 14.
** On April 14, detection of SARS-CoV-2 in nasopharyngeal swabs or by positive serology test for immunoglobulin A, G or M.
*** Symptomatic patients between March 11 and May 3, 2020.
The authors cautiously suggested that quantitatively reducing the viral inoculum received by SARS-CoV-2 virgin recipients not only reduced the probability of infection but also could have caused asymptomatic infections in others while still being able to induce an immunological response (Bielecki 2020), and idea that was later echoed by Monica Gandhi and George W. Rutherford (Ghandi 2020).
If genes offer no protection, behavior may. In the coming winter 2020/2021 months, face covering is paramount. After a year of SARS-CoV-2 experience, masks have been shown to decrease transmission both in health care settings and in the wider community (Chu DK 2020, Chou R 2020, Lee JK 2020). In March 2020, the Mass General Brigham, the largest health care system in Massachusetts (12 hospitals, > 75,000 employees), implemented universal masking of all HCWs and patients with surgical masks. During the pre-intervention period, the SARS-CoV-2 positivity rate increased exponentially, with a case doubling time of 3.6 days. During the intervention period, the positivity rate decreased linearly from 14.65% to 11.46% (Wang X 2020). In Paris, in a 1500-bed adult and a 600-bed pediatric setting of a university hospital, the total number of HCW cases peaked on March 23rd, then decreased slowly, concomitantly with a continuous increase in preventive measures (including universal medical masking and PPE) (Contejean 2020). In Chennai, India, before the introduction of face shields, 12/62 workers were infected while visiting 5880 homes with 31,164 persons (222 positive for SARS-CoV-2). After the introduction of shields among 50 workers (previously uninfected) who continued to provide counseling, visiting 18,228 homes with 118,428 persons (2682 positive), no infection occurred (Bhaskar 2020). These preventive measures are not new to medicine – surgeons have been using personal protective equipment (PPE) for more than a century (Stewart 2020). The wearing of masks by adults also remains critical to reducing transmission in child-care settings (Link-Gelles 2020). Under certain circumstances, it is even recommended between household members (Wang Y 2020).
Masks work even with super-emittors. By measuring outward emissions of micron-scale aerosol particles by healthy humans performing various expiratory activities, one group found that both surgical masks and unvented KN95 respirators reduced the outward particle emission rates by 90% and 74% on average during speaking and coughing. These masks similarly decreased the outward particle emission of a coughing super-emitter, who for unclear reasons emitted up to two orders of magnitude more expiratory particles via coughing than average (Asadi 2020).
After visualizing the flow fields of coughs under various mouth covering scenarios, a recently published study (Simha 2020) found that
- N95 masks are the most effective at reducing the horizontal spread of a cough (spread: 0.1 and 0.25 meters).
- A simple disposable mask can reduce the spread to 0.5 meters, while an uncovered cough can travel up to 3 meters.
- Coughing into the elbow is not very effective. Unless covered by a sleeve, a bare arm cannot form the proper seal against the nose necessary to obstruct airflow and a cough is able to leak through any openings and propagate in many directions.
Although the data regarding the effectivity of face masks is now clear, will everyone understand, i.e., even individuals with a still functioning working memory? If some individuals continue to put themselves at risk of SARS-CoV-2 infection (as well as their friends and relatives in case of infection), what factors might influence risk for COVID-19 exposure among young adults? In a remote US county, the drivers of behaviors were low severity of disease outcome; peer pressure; and exposure to misinformation, conflicting messages, or opposing views regarding masks (Wilson 2020). A scientifically inspired national prevention policy will be needed to counter misinformation and – let’s speak frankly for just two seconds! – address human stupidity. First, public health officials need to ensure that the public understands clearly when and how to wear cloth face coverings properly. Second, innovation is needed to extend physical comfort and ease of use. Third, the public needs consistent, clear, and appealing messaging that normalizes community masking (Brooks 2020). A small adaption in our daily lives relies on a highly effective low-tech solution that can help turn the tide.
The transmission setting, i.e., the actual place where the transmission of SARS-CoV-2 occurs, is the final element in the succession of events that leads to the infection of an individual. High population density that facilitates super-spreading events is key to widespread transmission of SARS-CoV-2. Transmission clusters, partly linked to super-spreader events, have been reported since the very beginning of the SARS-CoV-2 pandemic. For detailed information about SARS-CoV-2 hotspots, see the chapter Epidemiology, Transmission Hotspots, page 23. Suffice it to present here a list of important outbreaks which have beem reported in predominantly indoor settings:
- Hospitals (at the beginning of the pandemic; Houlihan 2020)
- Nursing facility, King County, Washington, 28 February (McMichael 2020)
- Business meeting, Southern Germany, 20-21 January (Rothe 2020)
- Medical advisory board meeting, Munich, Germany, 20-21 (Hijnen 2020)
- Cruise Ship, Yokohoma, Japan, 4 February (Rocklov 2020)
- Church meeting, Daegu, Korea, 9 and 16 February (Kim 2020)
- Religious gathering, Mulhouse, France, 17-24 February (Kuteifan 2020, Gerbaud 2020)
- Aircraft carriers: Theodore Roosevelt (Payne 2020) + Charles-de-Gaulle, March (Le Monde)
- Prisons (Kennedy 2020, Maxmen 2020, Wang EA 2020)
- Meat-processing and livestock plants (Günther 2020, Waltenburg 2020, Taylor 2020)
- Homeless shelters (Baggett 2020, Mosites 2020)
- Call center (Park SY 2020)
- Marriage (Mahale 2020)
- Funeral (Kant 2020)
- Choir (Hamner 2020, Alsveld 2020)
- Concert (Plautz 2020)
- Nightclubs (Kang 2020, Muller 2020)
- Bars (Chau NVV)
- Restaurants (Lu J 2020)
- Sports meetings (Atrubin 2020)
As with other respiratory viruses, the majority of SARS-CoV-2 infections occur at home where people live in close contact many hours a day, meeting multiple individuals (Read 2014). In a study from South Korea, household contacts accounted for 57% of identified secondary infections, despite exhaustive tracking of community contacts (Park YJ 2020). Globally, the secondary attack-rates (SARs) in households is around 20% (Madewell 2020), spouses being twice as likely to be infected as other adult household members. Household SARs also seem to be higher from symptomatic index cases than asymptomatic index cases, and to adult contacts than child contacts. With suspected or confirmed infections referred to isolate at home, household transmission will continue to be a significant source of transmission (Madewell 2020). Other settings which favor daily close and prolonged contact include nursing homes, prisons (Njuguna 2020), homeless shelters and worker dormitories where infection rates in excess of 60% have been reported. The risk of indoor transmission may be up to 20 times higher that transmission of SARS-CoV-2 in an outdoor setting (Bulfone 2020).
Indoor environments are SARS-CoV-2’s preferred playgrounds. In one modeling study, the authors estimated that viral load concentrations in a room with an individual who was coughing frequently were very high, with a maximum of 7,44 million copies/m3 from an individual who was a high emitter (Riediker 2020). However, regular breathing from an individual who was a high emitter was modeled to result in lower room concentrations of up to 1248 copies/m3. They conclude that the estimated infectious risk posed by a person with typical viral load who breathes normally was low and that only a few people with very high viral load posed an infection risk in the poorly ventilated closed environment simulated in this study.
Viable virus from air samples was isolated from samples collected 2 to 4.8 meters away from two COVID-19 patients (Lednicky 2020). The genome sequence of the SARS-CoV-2 strain isolated was identical to that isolated from the NP swab from the patient with an active infection. Estimates of viable viral concentrations ranged from 6 to 74 TCID50 units/L of air. During the first months of the pandemic, most clusters were found to involve fewer than 100 cases, with the exceptions being in healthcare (hospitals and elderly care), large religious gatherings and large co-habitation settings (worker dormitories and ships). Other settings with examples of clusters between 50–100 cases in size were schools, sports, bars, shopping centers and a conference (Leclerc 2020).
Closed doors and windows and poor ventilation favored SARS-CoV-2 transmission in churches and bars (James 2020, Furuse Y 2020). Opening windows and allowing better air movement may lead to lower secondary household transmission (Wang Y 2020).
Transportation in closed spaces – by bus, train or aircraft – has been shown to transmit SARS-CoV-2 at various degrees, depending on face mask use and time of travel. One paper describes a bus ride in a vehicle 11.3 meters long and 2.5 meters wide with 49 seats, fully occupied with all windows closed and the ventilation system on during the 2,5-hour trip. Among the 49 passengers (including the driver) who shared the ride with the index person, eight tested positive and eight developed symptoms. The index person sat in the second-to-last row, and the infected passengers were distributed over the middle and rear rows (Luo K 2020). An even more informative paper describes 68 individuals (including the source patient) taking a bus on a 100-minute round trip to attend a worship event. In total, 24 individuals (35%) received a diagnosis of COVID-19 after the event. The authors were able to identify seats for each passenger and divided bus seats into high-risk and low-risk zones (Shen Y 2020). Passengers in the high-risk zones had moderately but non-significantly higher risk of getting COVID-19 than those in the low-risk zones. On the 3-seat side of the bus, except for the passenger sitting next to the index patient, none of the passengers sitting in seats close to the bus window developed infection. In addition, the driver and passengers sitting close to the bus door also did not develop infection, and only 1 passenger sitting by an operable window developed infection. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Lesson learned for the future? If you take the bus, choose seats near a window – and open it!
To answer the question how risky train traveling is in the COVID-19 era, one group analyzed passengers in Chinese high-speed trains. They quantified the transmission risk using data from 2334 index patients and 72,093 close contacts who had co-travel times of 0–8 hours from 19 December 2019 through 6 March 2020. Unsurprisingly, travelers adjacent to an index patient had the highest attack rate (3.5%) and the attack rate decreased with increasing distance but increased with increasing co-travel time. The overall attack rate of passengers with close contact with index patients was 0.32% (Hu M 2020).
A review about in-flight transmission of SARS-CoV-2 found that the absence of large numbers of confirmed and published in-flight transmissions of SARS-CoV was encouraging but not definitive evidence that fliers are safe (Freedman 2020). At present, based on circumstantial data, strict use of masks appears to be protective. In previous studies, SARS-CoV-2 transmission has been described onboard aircrafts (Chen J 2020, Hoehl 2020). Note that if you don’t wear a mask, business class will not protect you from infection. A Vietnamese group report on a cluster among passengers on VN54 (Vietnam Airlines), a 10-hour commercial flight from London to Hanoi on March 2, 2020 (at that time, the use of face masks was not mandatory on airplanes or at airports) (Khanh 2020). Affected persons were passengers, crew, and their close contacts. The authors traced 217 passengers and crew to their final destinations and interviewed, tested, and quarantined them. Among the 16 persons in whom SARS-CoV-2 infection was detected, 12 (75%) were passengers seated in business class along with the only symptomatic person (attack rate 62%). Seating proximity was strongly associated with increased infection risk (risk ratio 7.3, 95% CI 1.2–46.2). Even more intriguing: a 7.5 h flight to Ireland, with a passenger occupancy of 17% (49/283 seats). The flight-associated attack rate was 9.8–17.8%, leading to 13 cases (Murphy 2020). A mask was worn during the flight by nine cases, not worn by one (a child), and unknown for three. Spread to 46 non-flight cases occurred country-wide.
Temperature and climate
SARS-CoV-1 (2003): The transmission of coronaviruses can be affected by several factors, including the climate (Hemmes 1962). Looking back to the 2003 SARS epidemic, we find that the stability of the first SARS virus, SARS-CoV, depended on temperature and relative humidity. A study from Hong Kong, Guangzhou, Beijing, and Taiyuan suggested that the SARS outbreak in 2002/2003 was significantly associated with environmental temperature. The study provided some evidence that there was a higher possibility for SARS to reoccur in spring than in autumn and winter (Tan 2005). It was shown that SARS-CoV remained viable for more than 5 days at temperatures of 22–25°C and relative humidity of 40–50%, that is, typical air-conditioned environments (Chan KH 2011). However, viability decreased after 24 h at 38°C and 80–90% relative humidity. The better stability of SARS coronavirus in an environment of low temperature and low humidity could have facilitated its transmission in subtropical areas (such as Hong Kong) during the spring and in air-conditioned environments. It might also explain why some Asian countries in the tropics (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community SARS outbreaks (Chan KH 2011).
SARS-CoV-2 (2020): At the beginning of the pandemic, is was unclear as to whether and to what extent climatic factors influence virus survival outside the human body and might influence local epidemics. SARS-CoV-2 is not readily inactivated at room temperature and by drying like other viruses, for example herpes simplex virus. One study mentioned above showed that SARS-CoV-2 can be detectable as an aerosol (in the air) for up to three hours, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel (van Doremalen 2020). A few studies suggested that low temperature might enhance the transmissibility of SARS-CoV-2 (Wang 2020b, Tobías 2020) and that the arrival of summer in the northern hemisphere could reduce the transmission of the COVID-19. In one study, after comparing 50 cities with (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain ; n=8) and without an important SARS-CoV-2 epidemic (n=42) in the first 10 weeks of 2020, areas with substantial community transmission of the virus had distribution roughly along the 30° N to 50° N latitude corridor with consistently similar weather patterns, consisting of mean temperatures of 5 to 11 °C combined with low specific and absolute humidity (Sajadi 2020). Cold working environments have been proposed to be considered as an occupational risk factor for COVID-19 (Cunningham 2020).
A possible association of the incidence of COVID-19 and both reduced solar irradiance and increased population density has been discussed (Guasp 2020). It was also reported that simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel plates while no significant decay was observed in darkness over 60 minutes (Ratnesar-Shumate 2020). However, another study concluded that transmission was likely to remain high even at warmer temperatures (Sehra 2020) and the epidemics in Brazil and India and the southern US – areas with high temperatures – soon tempered hopes that COVID “simply disappears like a miracle”. Warm and humid summer conditions alone are not sufficient to limit substantially new important outbreaks (Luo 2020, Baker 2020, Collins 2020).
Recently, one group found a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of Ultraviolet-B (UVB) in mitigating COVID-19 deaths (Moozhipurtath 2020). If confirmed via clinical studies, the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention would be attractive.
Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented (Meyerowitz 2020). After suspected or confirmed SARS-CoV-2 infection, people should quarantine until
- 10 days since symptoms first appeared
- 24 hours with no fever without the use of fever-reducing medications
- Other symptoms of COVID-19 are improving (exception: loss of taste and smell which may persist for weeks or months after recovery and need not delay the end of isolation).
(Note that these recommendations do not apply to immunocompromised persons or persons with severe COVID-19. Find more information at https://bit.ly/3qB62IR [CDC]).
Health authorities should know that SARS-CoV-2 infected individuals do not need to be quarantined for weeks. Persistently positive RT-PCRs generally do not reflect replication-competent virus. SARS-CoV-2 infectivity rapidly decreases to near-zero after about 10 days in mild-to-moderately-ill patients and 15 days in severely-to-critically-ill and immunocompromised patients (Rhee 2020). Of note, RT-PCR cycle threshold (Ct) values (a measure for viral load) correlated strongly with cultivable virus. In one study, the probability of culturing virus declined to 8% in samples with Ct > 35 and to 6% (95% CI: 0.9–31.2%) 10 days after onset; it was similar in asymptomatic and symptomatic persons (Singanayagam 2020). A recently published meta-analysis of 79 studies (5340 individuals) concluded that no study detected live virus beyond day 9 of illness, despite persistently high viral loads (Cevik 2020). In individuals who had mildly or moderately symptomatic SARS-CoV-2 infection and who present no symptoms for at least two days, a positive RT-PCR test 10 days or more after the first symptoms does not indicate infectiousness (‘post-infectious PCR-positivity’; Mina 2020).
In most countries (for example, Germany, USA), health authorities do not require a negative SARS-CoV-2 RT-PCR test to end the quarantine. Autorities in Italy or other countries that even in late November continued quarantining people at home for two, three, four weeks or longer because of continuously positive RT-PCR results should take note.
Find a detailed discussion of SARS-CoV-2 prevention in the corresponding chapter on page 119.
For everyday life, the following five rules of thumb are helpful:
- Avoid crowded places (more than 5-10 people). The more people are grouped together, the higher the probability that a superspreader is present who emits infectious particles tens or hundreds times more than a ‘normally’ contagious individual. Avoid funerals, and postpone religious services including weddings, baptisms, circumcisions, as well as team sports and choir singing until after the pandemic.
- Avoid in particular crowded and closed spaces (even worse: air-conditioned closed places where ‘old air’ is being moved around). In a room where a SARS-CoV-2 infected individual is coughing frequently, viable virus can be isolated from samples collected 2 to 4,8 meters away. Strangers or unacquainted persons should not meet in crowded or closed spaces.
- Avoid in all circumstances crowded, closed and noisy spaces where people must shout to communicate. Shouting or speaking loudly emits a continuous flow of aerosols that linger in the air for minutes. Intimate conversation in a noisy and crowded room, with people shouting at one another at a distance of 30 centimeters, inhaling deep into theirs lungs the exhalations of the person they are speaking to/shouting at for 5, 10, 20 minutes or longer is, from the virus’s point of view, the best conceivable transmission setting. Noise from machines or music around people grouped in a closed environment also creates the perfect setting for a superspreader event.
- Outside crowded, closed or noisy spaces, keep a distance of 2 meters to other people.
- Always wear a fask mask in public spaces. A face mask is a highly effective low-tech solution that can help contain local SARS-CoV-2 outbreaks. Face masks are not new to medicine – surgeons have been using them for more than a century. Next time you are unhappy when wearing a face mask, watch this video and enjoy the fact that unlike the doctors who might one day treat you for COVID-19 or other ailments, you won’t never have to put on and remove protective gear in a hospital.
Those who doubt the effectiveness of face masks might extract precious information from Figure 2. The cumulative number of confirmed COVID-19 cases in different countries – presented per million population – is intriguing. What did Japan, South Korea, Taiwan and Vietnam right that the other countries didn’t? The most probable explanation is
- Better testing
- Efficient contract tracing and isolation
- Early use of face masks
Figure 2. Cumulative confirmed COVID-19 cases per million people. What did Japan, South Korea, Taiwan and Vietnam do right that the other countries didn’t? Better testing, efficient contract tracing and isolation, and early use of face masks. Source: Our World in Data.