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. 2020 Jun 22:9:e57149.
doi: 10.7554/eLife.57149.

Evidence for transmission of COVID-19 prior to symptom onset

Lauren C Tindale #  1 , Jessica E Stockdale #  2 , Michelle Coombe  1 , Emma S Garlock  2 , Wing Yin Venus Lau  2 , Manu Saraswat  1 , Louxin Zhang  3 , Dongxuan Chen  4   5 , Jacco Wallinga  4   5 , Caroline Colijn  2
Affiliations

Evidence for transmission of COVID-19 prior to symptom onset

Lauren C Tindale et al. Elife. .

Abstract

We collated contact tracing data from COVID-19 clusters in Singapore and Tianjin, China and estimated the extent of pre-symptomatic transmission by estimating incubation periods and serial intervals. The mean incubation periods accounting for intermediate cases were 4.91 days (95%CI 4.35, 5.69) and 7.54 (95%CI 6.76, 8.56) days for Singapore and Tianjin, respectively. The mean serial interval was 4.17 (95%CI 2.44, 5.89) and 4.31 (95%CI 2.91, 5.72) days (Singapore, Tianjin). The serial intervals are shorter than incubation periods, suggesting that pre-symptomatic transmission may occur in a large proportion of transmission events (0.4-0.5 in Singapore and 0.6-0.8 in Tianjin, in our analysis with intermediate cases, and more without intermediates). Given the evidence for pre-symptomatic transmission, it is vital that even individuals who appear healthy abide by public health measures to control COVID-19.

Keywords: COVID19; Sars-CoV-2; coronavirus; epidemiology; global health; incubation; serial interval; transmission.

Plain language summary

The first cases of COVID-19 were identified in Wuhan, a city in Central China, in December 2019. The virus quickly spread within the country and then across the globe. By the third week in January, the first cases were confirmed in Tianjin, a city in Northern China, and in Singapore, a city country in Southeast Asia. By late February, Tianjin had 135 cases and Singapore had 93 cases. In both cities, public health officials immediately began identifying and quarantining the contacts of infected people. The information collected in Tianjin and Singapore about COVID-19 is very useful for scientists. It makes it possible to determine the disease’s incubation period, which is how long it takes to develop symptoms after virus exposure. It can also show how many days pass between an infected person developing symptoms and a person they infect developing symptoms. This period is called the serial interval. Scientists use this information to determine whether individuals infect others before showing symptoms themselves and how often this occurs. Using data from Tianjin and Singapore, Tindale, Stockdale et al. now estimate the incubation period for COVID-19 is between five and eight days and the serial interval is about four days. About 40% to 80% of the novel coronavirus transmission occurs two to four days before an infected person has symptoms. This transmission from apparently healthy individuals means that staying home when symptomatic is not enough to control the spread of COVID-19. Instead, broad-scale social distancing measures are necessary. Understanding how COVID-19 spreads can help public health officials determine how to best contain the virus and stop the outbreak. The new data suggest that public health measures aimed at preventing asymptomatic transmission are essential. This means that even people who appear healthy need to comply with preventive measures like mask use and social distancing.

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Conflict of interest statement

LT, JS, MC, EG, WL, MS, LZ, DC No competing interests declared, JW, CC Reviewing editor, eLife

Figures

Figure 1.
Figure 1.. Singapore COVID-19 cases.
(a) Daily hospitalized cases and cumulative hospitalized and discharged cases. (b) Daily incidence with probable source of infection. (C) Disease timeline, including dates at which each case is unexposed, exposed, symptomatic, hospitalized, and discharged. Not all cases go through each status as a result of missing dates for some cases.
Figure 2.
Figure 2.. Tianjin COVID-19 cases.
(a) Daily and cumulative confirmed cases, cumulative discharges and daily death cases. (b) Daily incidence with probable source of infection. (c) Disease progression timeline; not all cases go through each status as a result of missing dates for some cases.
Figure 3.
Figure 3.. Fitted gamma COVID-19 incubation period distributions (without intermediates).
Cases are defined as ‘early’ if they have symptom onset on or prior to January 31, and are classified ‘late’ otherwise.
Figure 4.
Figure 4.. COVID-19 incubation period Kaplan-Meier curves for (a) Singapore and (b) Tianjin.
Top panels show unstratified data (all cases with symptom onset given). Bottom panels show ‘early’ and ‘late’ cases, where early cases are defined as those with symptom onset on or prior to January 31, and late otherwise.
Figure 5.
Figure 5.. Mean incubation period and generation time estimates from the incubation period intermediates analysis, under the assumption that the scale parameter for both distributions is equal, shown with dependence on the mean number of unknown intermediate cases per day of the empirical time elapsed between exposure and symptom onset.
The incubation period is longer than the generation time, so this analysis suggests that symptom onset occurs after infectiousness begins. Top: Singapore. Bottom: Tianjin. The means are the scale times the shape, which is fixed at 2.1 in Singapore and 2.2 in Tianjin. Varying this fixed value for the shape parameter was not found to significantly impact the results.
Figure 6.
Figure 6.. Serial intervals of possible case pairs in (a) Singapore and (b) Tianjin.
Pairs represent a presumed infector and their presumed infectee plotted by date of symptom onset. Cases are defined as 'early' if they have symptom onset on or prior to January 31st.
Figure 7.
Figure 7.. Network diagram for (a) Singapore (b) Tianjin.
Figure 8.
Figure 8.. Pre-symptomatic infection as estimated by samples of (serial interval - incubation period), accounting for covariation.
Top: Singapore. Bottom: Tianjin. Left: without intermediates. Right: accounting for intermediates. Grey vertical line: 0. Samples below zero indicate pre-symptomatic transmission. In all cases there is substantial pre-symptomatic transmission.
Appendix 1—figure 1.
Appendix 1—figure 1.. Bootstrap values of the mean serial interval for (left) Singapore and (right) Tianjin, based on 100 replicates using the first four cases in each cluster.
See this image and copyright information in PMC

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