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Review
. 2020 Aug 5;10(8):e039856.
doi: 10.1136/bmjopen-2020-039856.

Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases

Andrew William Byrne  1 , David McEvoy  2 , Aine B Collins  3   4 , Kevin Hunt  5 , Miriam Casey  3 , Ann Barber  3 , Francis Butler  5 , John Griffin  4 , Elizabeth A Lane  3   4 , Conor McAloon  6 , Kirsty O'Brien  7 , Patrick Wall  8 , Kieran A Walsh  7 , Simon J More  3
Affiliations
Review

Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases

Andrew William Byrne et al. BMJ Open. .

Abstract

Objectives: Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach.

Design: Rapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics.

Information sources: Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases.

Results: There was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5-9.5 days. Median presymptomatic infectious period across studies varied over <1-4 days. Estimated mean time from symptom onset to two negative RT-PCR tests was 13.4 days (95% CI 10.9 to 15.8) but was shorter when studies included children or less severe cases. Estimated mean duration from symptom onset to hospital discharge or death (potential maximal infectious period) was 18.1 days (95% CI 15.1 to 21.0); time to discharge was on average 4 days shorter than time to death. Viral dynamic data and model infectious parameters were often shorter than repeated diagnostic data.

Conclusions: There are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.

Keywords: epidemiology; infectious diseases; public health; virology.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Simulation of the parameter distribution inferred for duration of infectious period for asymptomatic cases (T2); inferred infectious period for Davies et al, grey/blue curve, Davies et al pink curve (model priors). Green curve: Ma et al. Histogram is the distribution of asymptomatic cases to two clear tests reported by Hu et al. Reference lines are point estimates reported from Zhou et al, Li et al and Tuite et al.
Figure 2
Figure 2
Simulation of the parameter distribution used for T3 (the duration of the pre-symptomatic infectious period for those infected individuals who subsequently develop symptoms). Curves represent simulated approximations of distributions, given information provided from primary literature. Vertical lines represent point estimates where distributions could not be inferred (see table 2). 1. Peak et al (posterior); 2. Davies et al(prior); 3. Rothe et al; 4. He et al; 5. Davies et al (prior); 6. Wei et al.
Figure 3
Figure 3
Forest plot of the mean duration from onset of symptoms to death or recovery (T5) based on virological studies.
Figure 4
Figure 4
Frequency distribution of T5, time from onset of symptoms to recovery (here hospital discharge or death), using patient level raw data from Kraemer et al (pink bars), Linton et al (purple bars) and Tindale et al (green bars). Blue solid line is the kernel density of the aggregated dataset. Dashed lines represent the mean and 95% CI from a random effects regression model.
Figure 5
Figure 5
Composite inferred model for cycle threshold (CT) value changes from serial RT-PCR testing for SARS-CoV-2; currently uncertain whether peak viral load typically occurs prior to, on or postsymptom onset (primary literature informing this model includes. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
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