Transmission

By Bernd Sebastian Kamps
& Christian Hoffmann

Please find the figures
in the free PDF.

Update 13 July

Aerosol transmission

On 9 July, 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 other words, SARS-CoV-2 is not only transmitted via (macro-)droplets greater than 5 µm in size and fomites, but also via microdroplets smaller than 5 µm. If this shift is proven to be right, SARS-CoV-2 may go down in history as the virus that unified the almost century-old dichotomy of droplets vs. aerosol transmission (Wells 1934). The merit goes to Lidia Morawska, Donald K. Milton and 237 other scientists who published on 6 July 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.)

Viruses are released during exhalation, talking, and coughing in micro-droplets small enough to remain aloft in the air and pose a risk of exposure at distances beyond 1 to 2 m from an infected individual (Morawska 2020b). During the COVID-19 pandemic, some clusters in choirs (Hamner 2020, Miller 2020), shopping malls (Cai 2020), restaurants (Li Y 2020 + Lu J 2020) and meat processing plants (Gütersloh, The Guardian) were best explained by aerosol transmission. Morawska, Milton et al. suggest 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.
  • 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
Transmission route Prevention
1. (Macro-)Droplets (> 5 µm) Face masks + social distancing
2. Aerosol (micro-droplets, ≤ 5µm) ·     Face masks

·     Improved ventilation
(open doors and windows; upgrade ventilation systems)

·     Improved air filtering

·     Avoidance of crowded and closed spaces

3. Fomites Handwashing

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).

 

Recognizing that SARS-CoV-2 is transmitted via aerosol has immediate consequences for healthcare management. 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.

Recognizing that SARS-CoV-2 is transmitted via aerosol has even more far-reaching consequences – personal, 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. For everyday life, the following five rules of thumb are helpful:

  1. Wear face masks in public spaces.
  2. Keep a distance of 2 (two!) meters to other people.
  3. Avoid crowded places (more than 5-10 people).
  4. Avoid in particular crowded and closed spaces (even worse: air-conditioned closed places where air is being moved around).
  5. Avoid in any circumstances crowded, closed and noisy spaces where people must shout to communicate. These are SARS-CoV-2’s preferred playgrounds.

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 friend and family (probably less than 10). Religious services and recreational activities such as team sport and choir singing might not be possible.

At the economic level, all activities which bring numerous people from outside the “friends-and-family-bubbles” together might be banned during new community outbreaks. Instead of complete lockdowns like those enacted during the spring of 2020 – and which are not economically sustainable –, partial lockdowns would target places where foreigners, 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. Re-opening schools in September will be a world-wide challenge.

 

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Introduction

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).

The Virus

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 67). There is no doubt that SARS-CoV-2 has a bright future – at least until the scientific community develops a safe and efficient vaccine (see the chapter Immunology, page 101).

SARS-CoV-2 and its kin

SARS-CoV-2 is a coronavirus like

  • SARS-CoV (its cousin of 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) which account for 15 to 30% of common colds.

The CAR group viruses are highly transmissible and produce about 15 to 30% of the 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 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 to reduce mortality – despite tests on thousands of patients. After 35 years of research, there is still no vaccine to prevent HIV infection.

Ecology of SARS-CoV-2

SARS-CoV-2 is present at high concentrations in the upper and lower respiratory tract (Zhu N 2020, Wang 2020, Huang 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). 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

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 presymptomatic patients (He 2020).

A key factor in the transmissibility of SARS-CoV-2 is the high level of virus 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).

Routes of Transmission

Respiratory droplets vs aerosol

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). These droplets can then be inhaled or land on surfaces where they can 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). Other people may come into contact with these droplets and get infected when they touch their nose, mouth or eyes (Wang Y 2020).

SARS-CoV-2 was thought to be transmitted primarily through larger droplet particles, > 5-10 μm in diameter, commonly referred to as respiratory droplets, which fall to the ground due to gravity. It is now widely accepted that the virus can also be transmitted via smaller particles, < 5μm in diameter, which are referred to as droplet nuclei or aerosols; some COVID-19 clusters in choirs (Hamner 2020, Miller 2020), shopping malls (Cai J 2020), restaurants (Li Y 2020 + Lu J 2020) and meat processing plants (Gütersloh, The Guardian) were best explained by aerosol transmission.

 

Figure 1. Transmission of a respiratory virus. 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. The second – aerosol – transmission is now recognized as a possibly relevant transmission route in the SARS-CoV-2 pandemic (WHO 20200709). Adapted from Morawska 2020. Art work: Félix Prudhomme; YouTube: IYENSS. (This and the following illustration are under free license if credited correctly.)

 

The current 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).”

Experimental support for aerosol transmission of SARS-CoV-2 comes from studies that visualize 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 show that the lifetime of a droplet can 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).

If SARS-CoV-2 is transmitted airborne over several meters, previous prevention recommendations of frequent hand-washing and maintaining a distance of at least one meter (arm’s length) (WHO 20200329) will not be sufficient. Instead, adequate control measures would include wearing suitable masks whenever infected persons may be nearby and providing adequate ventilation of enclosed spaces where such persons are known to be or may recently have been (Morawska 2020, Somsen 2020, Meselson 2020). Infrastructure may have to be adjusted, for example, Heating, Ventilation and Air Conditioning Systems (HVAC) in buildings and on ships (Correia 2020, Gormley 2020). Most of all, tighter prevention recommendations will have unforeseeable consequences for all places where foreigners, strangers or simply unacquainted people meet. SARS-CoV-2 will thus continue to impact cultural and economic life – theaters, cinemas, bars, restaurants, shops, etc – for some time to come.

Fomites

It is currently unclear whether and to which extent transmission of via fomites (e.g., elevator buttons, hand rails, restroom taps) is epidemiologically relevant (Cai J 2020) or if the chance of transmission through inanimate surfaces is very small, and 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).  (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). There is some evidence that a protein-rich medium like airway secretions could protect the virus when it is expelled and may enhance its persistence and transmission by contaminated fomites (Pastorino 2020).

In my opinion, the chance of transmission through inanimate surfaces is very small, and 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).

Mother-to-child

Mother-to-child transmission doesn’t seem to be a prominent route of SARS-CoV-2 transmission. There is one report of a newborn with elevated SARS-CoV-2 IgM antibodies who was exposed for 23 days from the time of the mother’s diagnosis of COVID-19 to delivery (Dong L 2020). However, there was no evidence for intrauterine vertical transmission among another group of nine women with COVID-19 pneumonia in late pregnancy (Chen H 2020).

Vaginal (n=24) versus elective cesarean (n=16) was addressed in a study from Northern Italy. In one case a newborn had a positive test after a vaginal operative delivery.

Two women with COVID-19 breastfed without a mask because infection was diagnosed in the post-partum period; their new-borns tested positive for SARS-CoV-2 infection. The authors conclude that although post-partum infection cannot be excluded with 100% certainty, vaginal delivery seems to be associated with a low risk of intrapartum SARS-CoV-2 transmission (Ferrazzi 2020).

SARS-CoV-2 has been found in breast milk (Wu Y 2020, Groß 2020, Bastug 2020). As of May 2020, the Italian Society on Neonatology (SIN), endorsed by the Union of European Neonatal & Perinatal Societies (UENPS), recommended breastfeeding as advisable if a mother previously identified as COVID-19-positive or under investigation for COVID-19 was asymptomatic or paucisymptomatic at delivery. On the contrary, when a mother with COVID-19 is too sick to care for the newborn, the neonate should be managed separately and fed freshly expressed breast milk (Davanzo 2020, Davanzo 2020b [Italian]). This guidance may be subject to change in the coming months.

Stool, urine

Although no cases of fecal-oral transmission of SARS-CoV-2 have been reported thus far, a study from Zhuhai reports prolonged presence of SARS-CoV-2 viral RNA in fecal samples. Of the 41 (55%) of 74 patients with fecal samples that were positive for SARS-CoV-2 RNA, respiratory samples remained positive for SARS-CoV-2 RNA for a mean of 17 days and fecal samples remained positive for a mean of 28 days after first symptom onset (Wu Y 2020). In another study, 22/133 patients, SARS–CoV-2 was still detected in the sputum or feces (up to 39 and 13 days, respectively) after pharyngeal swabs became negative (Chen 2020). In still another study, seven out of ten children contained SARS-CoV-2 virus RNA in their fecal specimens, despite all patients showing negative results in respiratory tract specimens and the median time from onset to being negative results in respiratory tract and fecal specimens was 9 days and 34.43 days, respectively (Du W 2020).

Until proof of the contrary, the possibility of fecal-oral transmission should not be excluded. Strict precautions must be observed 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.

Blood products

SARS-CoV-2 is rarely detected in blood (Wang W 2020, Wolfel 2020). After screening of 2,430 donations in real-time (1,656 platelet and 774 whole blood), authors from Wuhan found plasma samples positive for viral RNA from 4 asymptomatic donors (Chang 2020). It remains unclear whether detectable RNA signifies infectivity.

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). More data are needed before transmission through transfusion can be declared safe.

Sexual 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).

Cats and dogs et al.

SARS-CoV-2 can be transmitted to cats and dogs. Two domestic cats with respiratory illnesses lasting 8 and 10 days were owned by persons with suspected or confirmed COVID-19 (Newman 2020). In one study, when inoculated with SARS-CoV-2, three cats transmitted the virus to three other cats. None of the cats showed symptoms, but all shedded virus for 4 to 5 days and developed antibody titers by day 24 (Halfmann 2020). 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).

Evidence of infection of animals with SARS-CoV-2 has been shown experimentally both in vivo and in vitro for monkeys, cats, 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).

Although it is too early to know if animals are potential intermediate hosts in chains of human–pet–human transmission, persons with COVID-19 should 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).

Transmission Event

Transmission of a virus from one person to another depends on four variables:

  1. The nature of the virus;
  2. The nature of the transmitter;
  3. The nature of the transmittee (the person who will become infected);
  4. The transmission setting.

Virus

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.

As mentioned above, SARS-CoV-2 can be viable for days (van Doremalen 2020). Environmental factors that might influence survival of the virus outside the human body will be discussed below (page 72).

The virologic determinants of more or less successful SARS-CoV-2 transmission are not yet fully understood.

Transmittor

Infectiousness seems to peak on or before symptom onset (He X 2020), with around half of secondary cases being possibly infected during the presymptomatic stage. The mean incubation 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, beyond that only in rare cases (Bai Y 2020).

In 230 HCW with non-severe COVID-19, viral loads declined by orders of magnitude within a few days of symptom onset. The only variable significantly associated with viral load was time from onset of symptoms (Shrestha 2020).

It is currently unknown if SARS-CoV-2 transmission correlates with the following characteristics of the index case (transmittor):

  • Symptom severity;
  • Large concentrations of virus in the upper and lower respiratory tract;
  • SARS-CoV-2 RNA in plasma;
  • In the future: reduced viral load due to drug treatment (as in people treated for HIV infection) [Cohen 2011, Cohen 2016, LeMessurier 2018])

SARS-CoV-2 transmission certainly correlates with a still ill-defined “super-spreader status” of the infected individual. For unknown reasons, some individuals – so-called super-spreaders – are remarkably contageous, 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 is more likely when the infected individual has few or no symptoms. 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); note that 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 presymptomatic or asymptomatic. Seventeen of 24 specimens (71%) from presymptomatic 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. It is assumed that about 50% of all infections occur through presymptomatic transmission (He X 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). Although the discovery of a pediatric inflammatory multisystem syndrome (PIMS) in SARS-CoV-2 infection in children (Verdoni 2020, Viner 2020, ECDC 15 May 2020) came as a surprise, the fact that children are susceptible to SARS-CoV-2 infection but frequently do not have notable disease raises the possibility that children could be an important source of viral transmission and amplification in the community. There is an urgent need for further investigation of the role children have in SARS-CoV-2 transmission chains (Kelvin 2020).

SARS-CoV-2 is highly transmissible, but given the right circumstances and the right prevention precautions, zero transmission can be achieved. 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).

Transmittee

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).

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). (The pathogenesis of COVID-19 will be discussed in an upcoming separate COVID Reference chapter.) Susceptibility to SARS-CoV-2 infection is probably influenced by the host genotype (Williams 2020). This would explain the higher percentage of severe COVID-19 in men (Piccininni 2020) and possibly the similar disease course in some twins in the UK (The Guardian, 5 May 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).

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 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
Soldiers 154 200 154 354
Tested* 88 130 51 181
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 suggest 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). Fools might soon extrapolate this thread of reasoning and envisage inoculation of infinitesimal amounts of SARS-CoV-2 in order to produce antibodies and develop a protective T cell response while remaining asymptomatic. Don’t tell your president!

Transmission setting

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 lead to the infection of an individual. High population density which facilitates super-spreading events (see also chapter Epidemiology, Transmission Hotspots, page 18) is key to widespread transmission of SARS-CoV-2.

Hospitals and other healthcare settings

In the early phase of the pandemic, hospitals and other health care centers have sometimes been hotspots of SARS-CoV-2 transmission, either because of ignorance or missing protective equipment. In a major London teaching hospital, 66/435 (15%) of COVID-19 inpatient cases between 2 March and 12 April 2020 were definitely or probably hospital-acquired through varied transmission routes (case fatality: 36%) (Rickman 2020).

In a prospective international multicentre cohort study of 1,718 healthcare workers participating in 5,148 at-risk tracheal intubation episodes, the overall incidence of the primary endpoint (lab‐confirmed COVID‐19 diagnosis or new symptoms requiring self‐isolation or hospitalisation) was 10.7% over a median follow‐up of 32 days (El-Boghdadly 2020).

In Greece, healthcare personnel represented approximately 10% of all notified COVID-19 cases. Those with high-risk occupational exposure to COVID-19 had increased probability of serious morbidity, healthcare seeking, hospitalization and absenteeism (Maltezou 2020).

In the University of Washington medical system and its affiliated organizations, between March 12 and April 23, a total of 3,477 symptomatic employees were tested; 185 (5.3%) employees tested positive for COVID-19. The prevalence of SARS-CoV-2 was similar when comparing frontline HCWs (5.2%) to non-frontline staff (5.5%) (Mani 2020).

Awaiting results from (difficult) randomised trials, the currently best available evidence suggests for all public and healthcare settings (Chu DK 2020) the FPE protection triad of

  • Physical distancing of at least 1 m, even better 2 m.
  • Face mask, ideally N95 or similar.
  • Eye protection (mandatory in health care settings and similar).

Find a helpful video, demonstrating the complex procedure for putting on and removing PPE as recommended by the CDC (Ortega 2020).

Indoor environments

Clusters of cases have been reported in many, predominantly indoor, settings. In a recent review, 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-habition 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).

The importance of indoor environments in SARS-CoV-2 infection has been shown beyond any doubt. In 318 clusters of three or more cases involving 1245 confirmed cases, only a single outbreak originated in an outdoor environment (Qian H 2020). In one study, the odds that a primary case transmitted COVID-19 in a closed environment was around 20 times greater compared to an open-air environment (Nishiura 2020).

Super-spreading events

Transmission of SARS-CoV and MERS-CoV 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). One group suggested that 80% of secondary transmissions could be caused by a small fraction of infectious individuals (around 10%). 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). 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 influenza (Endo 2020, Miller 2020, On Kwok 2020).

Transmission clusters, partly linked to super-spreader events, have been reported since the very beginning of the SARS-CoV-2 pandemic:

A study of 1,407 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).

Temperature and climate

Another variable still poorly understood is ambient temperature and humidity.

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): It is as yet 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 suggest that low temperature might enhance the transmissibility of SARS-CoV-2 (Triplett 2020; Wang 2020b, Tobías 2020) and that the arrival of summer in the northern hemisphere could reduce the transmission of the COVID-19. 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 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). In particular the current epidemics in Brazil and India and the southern US – areas with high temperatures – should temper hopes that COVID “simply disappears like a miracle”. Warm and humid summer conditions alone might be unlikely to limit substantially new important outbreaks (Luo 2020, Baker 2020, Collins 2020).

Outlook

Less than 6 months after the first SARS-CoV-2 outbreak in China, the transmission dynamics driving the pandemic are coming into focus.

It now appears that a high percentage (as high as 80%?) of secondary transmissions could be caused by a small fraction of infectious individuals (as low as 10%?; Endo 2020); if this is the case, then the more people are grouped together, the higher the probability that a superspreader is part of the group.

It is now acknowledged that aerosol transmission might play an important role in SARS-CoV-2 transmission (WHO 20200709, Prather 2020); if this is the case, then building a wall around this same group of people and putting a ceiling above them further enhances the probability of SARS-CoV-2 infection.

It finally appears that shouting and speaking loudly emits thousands of oral fluid droplets per second which could linger in the air for minutes (Anfinrud 2020, Stadnytskyi 2020, Chao 2020, Asadi 2019); if this is the case, then creating noise (machines, music) around people grouped in a closed environment would create the perfect setting for a superspreader event.

Over the coming months, the scientific community will try and

  • define more precisely the role of aerosols in the transmission of SARS-CoV-2;
  • unravel the secrets of super-spreading;
  • advance our understanding of host factors involved in the successful “seeding” of SARS-CoV-2 infection;
  • elucidate the role of children in the transmission of the virus at the community level;
  • continue to describe the conditions under which people should be allowed to gather in larger groups;

Without a coronavirus vaccine, nobody will return to a “normal” pre-2020 way of life. The most promising exit strategy for the coronavirus crisis is an efficient vaccine that can be rolled out safely and affordably to billions of people. Thousands of researchers are working around the clock, motivated by fame (becoming the next Dr. Salk?) and money (becoming the next Scrooge McDuck?). However, despite these efforts, it is not even certain that developing a COVID-19 vaccine is possible (Piot 2020, cited by Draulens). Until the worldwide availability of a vaccine, the only feasable prevention scheme is a potpourri of physical distancing (Kissler 2020), intensive testing, case isolation, contact tracing, quarantine (Ferretti 2020) and, as a last (but not impossible) resort, local lockdowns.

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