Transmission of COVID-19

Viral shedding

Over the course of the infection, the RNA of the virus has been identified in respiratory tract specimens 1-2 days before the onset of symptoms and it can persist for up to eight days in mild cases [118], and for longer periods in more severe cases, peaking in the second week after infection [111,118]. Prolonged viral RNA shedding has been reported from nasopharyngeal swabs (up to 63 days among adult patients)[119] and in faeces (more than one month after infection in paediatric patients) [120]. 

Late viral RNA clearance (≥15 days after illness onset), is associated with male sex, old age, hypertension, delayed admission to hospital, severe illness at admission, invasive mechanical ventilation, and corticosteroid treatment [121]. 

Detection of viral RNA by PCR does not equate with infectivity, unless infectious virus particles have been confirmed through virus isolation and cultured from the particular samples. Viral load can however be a potentially useful marker for assessing disease severity and prognosis: a recent study indicated that viral loads in severe cases were up to 60 times higher than in mild cases [111].

In terms of viral load profile, SARS-CoV-2 is similar to that of influenza, which peaks at around the time of symptom onset [122,123], but contrasts with that of SARS-CoV, which peaks at around 10 days after symptom onset, and that of MERS-CoV which peaks at the second week after symptom onset. Older age has also been associated with higher viral loads [123]. The high viral load close to symptom onset suggests that SARS-CoV-2 can be easily transmissible at an early stage of infection [52]. 

Viral RNA has been detected in faeces [120] [124], whole blood [125,126], serum [76,127], saliva [76,127], nasopharyngeal specimens [128], urine [129]; ocular fluid [129,130], breastmilk [74] and in placental or foetal membrane samples [131]. A correlation has been suggested between the isolation of viable virus and the initial viral load (i.e. cycle threshold [Ct]) [132]. 

Data from Germany show that in symptomatic children, initial SARS-CoV-2 viral loads at diagnosis are comparable to those in adults [118], and that symptomatic children of all ages shed infectious virus in early acute illness [133]. 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. 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 [134]. 

Virus and substances of human origin (SoHO)

There were so far no reports of transmission of COVID-19 through substances of human origin (SoHO). More evidence is needed to assess the importance of recent findings of viral RNA in seminal fluid [135] and breast milk [74] for the safety of their donation, since the infectivity of detectable RNA in breast milk and seminal fluid has not been proven. Three organisations in reproductive medicine have jointly issued a statement on the resumption of fertility treatment that had been discontinued in March [136]. Recommendations in the first update of the ECDC’s technical document on the safety of SoHO supply in EU/EEA remain valid [137].

The collection and clinical use of convalescent plasma for the treatment of COVID-19 patients is ongoing in the EU/EEA and the USA within clinical studies or as an emergency compassionate use. In EU/EEA Members States, these activities are carried out according to EC guidance developed in collaboration with ECDC, national competent authorities and other stakeholders [138]. The early studies showed that convalescent plasma infusion to COVID-19 patients is safe and effective [139,140]. As of 29 May 17 674 units of convalescent plasma have been infused to COVID-19 patients in the USA [141]. 

Role of asymptomatic and pre-symptomatic individuals

Asymptomatic infection at time of laboratory confirmation has been reported from many settings [52,142-147]. Some of these cases developed some symptoms at a later stage of infection [148,149]. In a recent review, the proportion of positive cases that remained asymptomatic was estimated at 16%, with a range from 6 to 41% [150]. In another systematic review, the pooled proportion of asymptomatic cases at time of testing was 25% [151]. A majority of these cases developed symptoms later on, with only 8.4% of the cases remaining asymptomatic throughout the follow-up period [151]. There are also reports of asymptomatic cases with laboratory-confirmed viral shedding in respiratory and gastrointestinal samples [148,152,153]. Similar viral loads in asymptomatic versus symptomatic cases have been reported, indicating the potential of virus transmission from asymptomatic patients [154]. 

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 [151,155]. Mathematical modelling studies (not peer-reviewed) have suggested that asymptomatic individuals might be major drivers for the growth of the COVID-19 pandemic [156,157]. 
Although transmission from asymptomatic carriers has been reported [158,159], the risk of transmission from pre-symptomatic or symptomatic patients is considered to be higher. Viral RNA shedding is higher at the time of symptom onset and declines after days or weeks [127].
Pre-symptomatic transmission (i.e. when the infector develops symptoms after transmitting the virus to another person) has been reported [147,160,161]. Exposure of secondary cases occurred 1–3 days before the source patient developed symptoms [161]. 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 [162]. 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) [163]. 

Major uncertainties remain with regard to the influence of pre-symptomatic transmission on the overall transmission dynamics of the pandemic because the evidence on transmission from asymptomatic cases from case reports is suboptimal. 

Transmission risks in different settings

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 [164], 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, trough 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  [165]. 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 for airborne transmission is considered less robust than the evidence for direct contact transmission between infected animals and naïve animals. 

Transmission in children and in school

Children most likely 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 [49,54,166,167]. 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 [46], 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 [47]. Two studies on household transmission estimated the household secondary attack rate (SAR) to be 16.3% [168] and 13.8% [169]. Age-stratified analysis showed that the SAR in children was 4.7% compared with 17.1% in adults (≥ 20 years of age) [168], and that the odds of infection in children was 0.26 times (95%CI 0.13-0.54) of that among the elderly (≥ 60 years of age) [169]. 

Child-to-adult transmission appears to be uncommon. There are few case reports, with poorly documented data, describing a paediatric case as potential source of infection for adults [120,170]. 

Crowded and confined indoor spaces

Several outbreak investigation reports have shown that COVID-19 transmission can be particularly effective in crowded, confined indoor spaces such as workplaces including factories, churches, restaurants, ski resorts, shopping centres, worker dormitories, cruise ships and vehicles, or events occurring indoor such as, parties,  and dance classes, [171]. They indicated that transmission can be linked with specific activities, such as singing in a choir [172] or religious services that may be characterised by increased production of respiratory droplets through loud speech and singing. 
In a study of 318 outbreaks in China, transmission in all cases except one occurred in indoor spaces [173]. The only case of outdoor transmission identified in this study involved two persons. However, outdoor events have also been implicated in the spread of COVID-19, typically those associated with crowding such as carnival celebrations [174] and football matches [175] suggesting a risk of transmission linked to crowding even at outdoor events. However, exposure in crowded indoor spaces is also very common during such events.  

The duration that people stay in indoor settings appears also to be associated with the attack rate. For example, 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%)[172]. 
An epidemiological investigation at a call centre in South Korea showed an attack rate of 43.5% among 216 employees on the 9th floor of the call centre indicating high transmission in crowded indoor workplace environment [176]. Most of the infected employees were sitting at the same side of the 9th floor which suggests the influence of proximity, but there was no obvious relation of risk of transmission and distance from the index case on this side of the 9th floor. The authors also conclude that the duration of contact played the most important role in spreading of COVID-19, since the cases were limited almost exclusively to the 9th floor despite interaction with colleagues in other settings (such as the elevators and lobby).
It is not possible to disentangle in these reports the role of physical proximity and direct contact through handshaking, or indirect transmission through contaminated objects and surfaces or longer distance transmission through aerosols. However, they illustrate the risk of transmission in crowded indoor settings and the importance of bundled prevention measures.
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 [177]. Distances of two metres provided an even larger protective effect and the use of respirators was found to be more protective than medical masks in this review.
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 [128].
Similarly, two other outbreaks from China in January 2020 attribute air conditioning systems using a re-circulating mode as a likely aid to transmission [178]. 

Schools

In the investigation of the first outbreak in France, one infected child attended three different schools while symptomatic and despite 112 contacts identified (including children and teachers), no symptomatic secondary cases were detected [179]. In a recent study from New South Wales, Australia, 863 close contacts of 18 COVID-19 cases (9 students and 9 staff) from 15 schools (10 high schools and 5 primary schools) were tested. Of these 863 close contacts, only two students have been identified as secondary cases. The secondary case in high school was presumed to have been infected following close contact with two student cases. The other secondary case was presumed to have been infected by a teacher who was a case. The investigation found no evidence of children infecting teachers [180]. 

Sports

Sporting events pose a potential risk from SARS-CoV-2 infection to athletes, coaches and spectators alike [181-184].  This is particularly an issue in certain settings where athletes train in groups, engage in contact sports, share equipment or use common areas, including locker rooms.  Moreover, community and individual-level recreational sport activities could also potentially heightened risk of spreading the coronavirus. Transmission could occur through person-to-person contact, exposure to a common-source or aerosols/droplets from an infected individual. 

Whether physical exertion per se increases the risk of infections to the athlete is controversial.  It has been speculated that vigorous exercise can temporarily suppress the immune function but this assertion has been questioned [185].  The return to vigorous exercise during convalescence has raised the concern of cardiac complications [183] but an association with SARS-CoV-2 infections has not been documented to date.  In light of the benefits of regular physical activity to physical and mental health it is important to remain active during the COVID-19 pandemic while respecting the physical distancing and personal hygiene recommendations [186]. 

Neither waterborne transmission of SARS-CoV-2 virus in humans, nor occurrence of SARS-CoV-2 virus in the seawater environment has been proven to date. Scientists from the Spanish National Research Council (CSIC) have released a report on the current state of knowledge about the transmission of the novel coronavirus in recreational areas used for bathing and other aquatic activities [36,37]. The report reviews the available scientific literature to give a series of recommendations. According to the CSIC findings, infection by SARS-CoV-2 through contact with water under usual bathing conditions is very unlikely during recreational activities.

 

References