Covid-19: Characterising The Distribution Of Incubation Time And Latency Time

Funders
Wellcome (OUCRU Core Grant)
University of Leiden

Principal Investigators:
Associate Professor Ronald Geskus
Dr Le Thanh Hoang Nhat
Dr Marc Choisy

Collaborator(s):
Dr Pham Quang Thai, National Institute of Hygiene and Epidemiology (NIHE)
Vera Arntzen, University of Leiden
Professor Marta Fiocco, University of Leiden

The length of the quarantine period is based on estimates of the incubation time distribution because data on the latency time is lacking. Our project filled this gap by estimating the latency time distribution. Furthermore, latency time and incubation time are important components for mathematical models that quantify and predict the spread of SARS-CoV-2.

Background

The time from infection to becoming infectious (latency time) and to developing symptoms (incubation time) are key characteristics of any infection. For SARS-CoV-2, data to estimate both quantities have not been collected in a systematic way. As a consequence, information is incomplete, and there is a high risk of bias. For most individuals, the exact time of infection is not known. At most, we have information on the exposure interval during which someone became infected. Also, a large percentage of individuals remains asymptomatic, and these individuals are more likely to be missed in data collection.

Study design

From the start of the pandemic until July 2021, Viet Nam has performed active contact tracing of all community infected individuals and quarantined these “F1 contacts” in supervised locations. Since March 2020, all individuals that entered Viet Nam have been quarantined. Vietnam has had four major outbreaks, caused by at least three different variants, the original variant, the alpha variant and the Delta variant. In collaboration with NIHE and the Ho Chi Minh City Centre for Disease Control, we combine data from different sources and outbreaks to create a unique data set with representative information on the initial stages of the SARS-CoV-2 infection and disease process.

Contact tracing data provides information on the window of exposure. For the latency time, we assume that individuals become infectious when SARS-CoV-2 RNA becomes detectable. This information is obtained from the longitudinal polymerase chain reaction (PCR) test results.

For the incubation time, we use the time when patients first report symptoms that are suggestive of SARS-CoV-2 infection; individuals that remain asymptomatic are excluded. Data on the latency time are doubly interval-censored. Not only the time origin (infection) but also the event time (detectable RNA) is at best known to lie within an interval: the presence of detectable RNA is known each time a PCR test is done. For the incubation time, we have exact information on the time of becoming symptomatic for most individuals; then, only the time origin is interval-censored. We estimate both distributions by maximising the likelihood for (doubly) interval-censored data. We compare estimates for the different variants.

Publications

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Thai Quang Pham, Maia Rabaa, Luong Huy Duong, Tan Quang Dang, Quang Dai Tran, Ha Linh Quach, Ngoc Anh Hoang, Dinh Cong Phung, Nghia Duy Ngu, Anh Tu Tran, Ngoc Quang La, My Phuc Tran, Chau Vinh, Khanh Cong Nguyen, Duc Anh Dang, Duong Nhu Tran, Guy E Thwaites, H Rogier van Doorn, Marc Choisy, OUCRU COVID-19 Research Group
Clin Infect Dis
August 1, 2020
DOI: 10.1093/cid/ciaa1130
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