Currently available evidence indicates that COVID-19 may be transmitted from person to person through several different routes. In the scoping review published by La Rosa et al [1], the human coronaviruses primary transmission mode is person-to-person contact through respiratory droplets generated by breathing, sneezing, coughing, etc., as well as contact (direct contact with an infected subject or indirect contact, through hand-mediated transfer of the virus from contaminated fomites to the mouth, nose, or eyes). Infection is understood to be mainly transmitted via large respiratory droplets containing the SARS-CoV-2 virus. Transmission through aerosols has also been implicated but the relative role of large droplets and aerosols is still unclear. Indirect transmission through fomites that have been contaminated by respiratory secretions is considered possible, although, so far, transmission through fomites has not been documented.

Evidence on SARS-CoV-2 transmission is available from a recent animal study on ferrets, which are considered suitable animal models for human respiratory infections, that assessed transmission in an experimental setting [2]. The findings suggest that direct transmission occurs between the animals, and the virus can be shed through multiple routes with rapid transmission to naive hosts in close contact with the infected hosts. The evidence of airborne transmission is considered less robust than the evidence of direct contact transmission between infected animals and naïve animals.

Role of asymptomatic and pre-symptomatic individuals

Asymptomatic infection at time of laboratory confirmation has been reported from many settings[3,24-30]. Some of these cases developed some symptoms at a later stage of infection [31,32]. In a recent review, the proportion of positive cases that remained asymptomatic was estimated at 16%, with a range from 6 to 41% [33]. In another systematic review, the pooled proportion of asymptomatic cases at time of testing was 25% [34]. A majority of these cases developed symptoms later on, with only 8.4% of the cases remaining asymptomatic throughout the follow-up period [34]. There are also reports of asymptomatic cases with laboratory-confirmed viral shedding in respiratory and gastrointestinal samples [30,31,35,36].

Asymptomatic infection in children has been described in several large case series from China, which reported 4% to 28% asymptomatic paediatric cases among cases tested based on symptoms, signs or contact tracing [37,38]. A systematic review presenting data on 2 914 paediatric patients with COVID-19 from China, Spain, Iran, the Republic of Korea and the United States identified 14.9% asymptomatic cases in children [39]. Others have reported 18% asymptomatic cases in a meta-analysis of 551 laboratory-confirmed cases in children [40] and 16% asymptomatic cases among a European cohort of 582 children [41].

Similar viral loads in asymptomatic versus symptomatic cases have been reported, indicating the potential of virus transmission from asymptomatic patients [30,42]. A community treatment center study (n=303) from Republic of Korea showed that RT-PCR Ct values for SARS-CoV-2 in asymptomatic patients (n=110, 36.3%) were similar to those in symptomatic patients [30]. The median time from diagnosis to the first negative RT-PCR conversion was 17 days for asymptomatic patients and 19.5 days for symptomatic (including pre-symptomatic) patients. Viral loads in asymptomatic patients from diagnosis to discharge tended to decrease more slowly than those in symptomatic (including pre-symptomatic) patients [30].

Asymptomatic transmission (i.e. when the infector has no symptoms throughout the course of the disease), is difficult to quantify. Available data, mainly derived from observational studies, vary in quality and seem to be prone to publication bias [34,43]. Mathematical modelling studies (not peer-reviewed) have suggested that asymptomatic individuals might be major drivers for the growth of the COVID-19 pandemic [44,45].

Pre-symptomatic transmission (i.e. when the infector develops symptoms after transmitting the virus to another person) has been reported [29,46,47]. Exposure of secondary cases occurred 1–3 days before the source patient developed symptoms [47]. It has been inferred through modelling that, in the presence of control measures, pre-symptomatic transmission contributed to 48% and 62% of transmissions in Singapore and China, respectively [48]. Pre-symptomatic transmission was deemed likely based on a shorter serial interval of COVID-19 (4.0 to 4.6 days) than the mean incubation period (five days) [49].

Major uncertainties remain with regard to the impact of pre-symptomatic transmission on the overall transmission dynamics of the pandemic, which is mainly based on the limited evidence on transmission from asymptomatic cases from case reports and modelling.

Transmission in children

Available evidence to date indicates that children most probably contract COVID-19 in their households or through contact with infected family members, particularly in countries where school closures and strict physical distancing has been implemented [50-55].

In a publication from Italy, exposure to SARS-CoV-2 from an unknown source or from a source outside the child’s family accounted for 55% of the cases of infection [54], while in another Italian cohort, contact with a SARS-CoV-2 infected person outside the family was rarely reported and 67.3% (113/168) of children had at least one parent who tested positive for SARS-CoV-2 infection [55]. Two studies on household transmission estimated the household secondary attack rate  to be 16.3% [56] and 13.8% [57]. Age-stratified analysis showed that the secondary attack rate   in symptomatic children was 4.7% compared with 17.1% in adults (≥ 20 years of age) [56], and that the probability of infection in children was 0.26 times lower (95%CI 0.13-0.54) than in elderly people (≥ 60 years of age) [57].

In a manuscript (as yet not peer reviewed) relating to contact tracing efforts carried out during school closures in Trento, Italy, the attack rate among contacts of 0-14 year old cases was 22.4%, which is higher than that of working-age adults (approximately 13.1%) [58]. In this study, not all asymptomatic contacts were tested. South Korea has permissive testing recommendations for contacts identified during contact tracing, meaning that more secondary cases are identified among children than in other settings. The attack rate among household contacts of index cases aged 0-9 years and 10-19 years was 5.3% and 18.6%, respectively, indicating transmission potential in both children and adolescents, and possibly more effective transmission in adolescents than in adults [59]. These results support the transmission potential of children, in household settings.

A recent report from US provides additional evidence of the role of children and adolescents in transmission. This study reported an overall attack rate of 44% among attendees (i.e. children, adolescents and adults) of an overnight camp where a teenage staff was the index case [60]. The age-stratified attack rates were 51% among those aged 6-10 years; 44% among those aged 11-17 years and 33% among those aged 18-21 years [60]. Asymptomatic infections were observed in 26% of those with available test results and symptom data[60]. These findings indicate that children and adolescents can spread efficiently the virus, particularly in an indoor and overnight setting.

Data from Germany showed that in symptomatic children, initial SARS-CoV-2 viral loads at diagnosis are comparable to those in adults [4], and that symptomatic children of all ages shed infectious virus in early acute illness. In this study, also infectious virus isolation success was comparable to that of adults. The youngest patient from whom SARS-CoV-2 was isolated was a seven-day old neonate [61]. In another non peer-reviewed publication, it was also shown that there is no significant difference between viral loads in persons 1-20 years of age in comparison to adults 21-100 years of age [62]. Further, another study suggests that the viral load in children below 5 years of age with mild to moderate COVID-19 symptoms is higher compared to older children and adults [39].

Transmission risks in different settings

Several outbreak investigation reports have shown that COVID-19 transmission can be particularly effective in crowded, confined indoor spaces[63] . Transmission can be linked with to specific activities, such as singing in a choir [64]. In a 2.5 hour choir practice in Washington, US, there were 32 confirmed and 20 probable secondary COVID-19 cases among 61 participants (85.2%)[64]. The duration of the indoor activity and the increased production of respiratory droplets through loud speech and singing, likely increased the risk of transmission.

Poor ventilation in confined indoor spaces is associated with increased transmission of respiratory infections and COVID-19 in particular [65]. In a restaurant outbreak of 10 cases in three families in Guangzhou, China,  transmission was attributed to the spread of respiratory droplets carrying SARS-CoV-2 by the airflow generated by the air-conditioning [15]. Similarly, two other outbreaks from China in January 2020 attribute air conditioning systems using a re-circulating mode as a likely aid to transmission [66]. Well-maintained, heating, ventilation, and air conditioning systems may have a complementary role in decreasing transmission in indoor spaces by increasing the rate of air change, decreasing recirculation of air and increasing the use of outdoor air [65].

Occupational settings

Multiple outbreaks of COVID-19 have been observed in several occupational settings within and beyond the EU/EEA and the UK, including slaughterhouses, meat processing plants, mines and building sites [63,67,68].  Possible factors contributing to clusters and outbreaks in occupational settings are:

• Working in confined indoor spaces: Studies have shown that in Europe >80% of working time is spent indoors and that variations in the socioeconomic and demographic status lead to different work-day patterns indoors [69]. Participating in meetings and sharing the same office space has been reported in literature as a risk factor for contracting COVID-19 [70,71].
• Lack of social distancing: Outbreaks in different workplaces have been described when there were difficulties maintaining the recommended distance of at least two metres [71,72]. Sharing facilities (e.g. canteen and dressing rooms ), transport and accommodation may also contribute to transmission [73].
• Close/direct contact with COVID-19 cases: Healthcare workers are known to be at greater risk of occupational exposure to biological agents, particularly infectious pathogens such as TB, influenza, SARS, measles etc. [74,75]. In a UK study of more than 120 000 employed persons, the risk of healthcare workers testing positive for COVID-19 was over seven times higher than for non-essential workers, and those in social care had a risk that was three times higher [76]. Further specific occupations which are probably at risk of exposure to COVID-19 include transport workers (taxi and bus drivers), sales people, postal/package delivery workers and domestic cleaners, due to the fact that they are exposed to multiple clients. A study from Sweden that looked at cases of COVID-19 diagnosed in different occupations found the highest risk among taxi drivers, with a relative risk of being diagnosed with COVID-19 that was 4.8 times higher than in all other professions (95% confidence interval 3.9-6) followed by bus and tram drivers (RR 4.3, 95% CI 3.6–5.1) [77].
• Insufficient or incorrect use of protective personal equipment (PPE): Some work sites where outbreaks have occurred have been slow to implement appropriate infection control and hygiene standards or have done so inadequately [78].  Insufficient access to PPE has been identified as an additional risk factor [79]. A systematic review and meta-analysis of 172 observational studies both in healthcare settings and the community, that looked into the effect of distance from the source patient and the use of respiratory and eye protection in the risk of transmission of SARS-CoV, MERS-CoV and SARS-CoV-2, concluded that physical distancing of at least one metre, use of face masks and eye protection were associated with a much lower risk of transmission [80].
• ‘Presenteeism” (i.e. reporting to work despite being symptomatic for a disease): Fear of losing their job or inability to reduce their working hours in order to stay home may lead to continued commuting and working, even when the employee or a family member are exhibiting symptoms compatible with COVID-19 [78].

Further information on outbreaks in occupational settings in the EU/EEA can be found in the ECDC technical report on this topic [81].

School settings

Child-to-child transmission: Available evidence appears to suggest that transmission among children in schools is less efficient for SARS-CoV-2 than for other respiratory viruses such as influenza [82]. However, this evidence is mainly derived from school outbreaks, which tend to rely on detecting symptomatic cases only and will therefore underestimate the number of infected, asymptomatic, and potentially infectious children in these outbreaks. No evidence of secondary cases among child or adult contacts of confirmed paediatric cases was found in contact tracing studies from France [83], Ireland [84] and Finland [85]. In Australia, a contact tracing study in 15 primary and high schools, where nine student COVID-19 cases were detected, found one secondary positive case in a primary school student (out of 735 close child contacts who were followed up) [86].

In Singapore, two preschools and one secondary school identified child index cases and tested close contacts. In a case where a preschool child was the index case (mean age 4.9 years), 34 preschool student contacts developed potential COVID-19 symptoms during the incubation period, however all 34 symptomatic cases tested negative for SARS-CoV-2. In a case where the index child was in secondary school (mean age 12.8 years), a total of eight out of 77 students developed symptoms and were screened for SARS-CoV-2 during the incubation period. All eight symptomatic student contacts from the school tested negative [87,88].

In Israel, a first large school outbreak emerged ten days after re-opening all schools with requirement for daily health reports, hygiene, face masks, social distancing and minimal interaction between classes. The first two cases were registered on 26 May and 27 May, having no epidemiological link. Testing of the complete school community revealed 153 students (attack rate: 13.2%) and 25 staff members (attack rate: 16.6%) who were COVID-19 positive. Overall, some 260 persons were infected (students, staff members, relatives and friends) [88].

Child-to-adult transmission: Currently available evidence indicates that children are not the primary drivers of SARS-CoV-2 transmission to adults in the school setting. Where COVID-19 in children was detected and contacts followed-up, no adult contacts in the school setting have been detected as SARS-CoV-2 positive during the follow-up period [84,86,89].

Adult-to-child transmission: There is very little documented evidence of potential transmission from adults to children within the school setting. In Ireland, three adult cases had a total of 102 child contacts that did not result in detection of any secondary child cases although, only symptomatic individuals were referred for follow-up testing [84]. The outbreak in a high school in Israel did not specify the age of the index cases, making identification of adult-to-student transmission within the school setting impossible without further information [88]. In Australia, a contact tracing study in 15 primary and high schools where nine staff-member-COVID-19 cases were detected found one secondary positive case in a secondary school student (among 735 child close contacts who were followed up) [86]. In Finland, following exposure to an infected teacher, seven out of 42 exposed students developed antibodies or were PCR positive, however household or community transmission may have been the source in some of these [85].

Adult-to-adult transmission: There is limited evidence within the peer-reviewed literature documenting transmission between adults within the school setting. Studies from Sweden [77] and Chile [90] indicate that adults are not at higher risk of SARS-CoV-2 within the school setting than the risk in the community or household.

Further information on role of children and school settings in COVID-19 transmission can be found in the ECDC technical report on this topic [91].

Source: ECDC