ABSTRACT
ObjectiveTo estimate the proportion of pre-symptomatic transmission of SARS-CoV-2 infection that can occur and timing of transmission relative to symptom onset. Setting/designSecondary analysis of international published data. Data sourcesMeta-analysis of COVID-19 incubation period and a rapid systematic review of serial interval and generation time, which are published separately. ParticipantsStudies were selected for analysis if they had transparent methods and data sources and they provided enough information to simulate full distributions of serial interval or generation time. Twenty-three estimates of serial interval and five of generation time from 17 publications were included. MethodsSimulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset were calculated and the proportion of pre-symptomatic transmission was estimated. Outcome measuresTransmission time of SARS-CoV-2 relative to symptom onset and proportion of pre-symptomatic transmission. ResultsTransmission time ranged from a mean of 2.91 (95% CI: 3.18-2.64) days before symptom onset to 1.20 (0.86-1.55) days after symptom onset. Unweighted pooling of estimates of transmission time based on serial interval resulted in a mean of 0.60 days before symptom onset (3.01 days before to 1.81 days after). Proportion of pre-symptomatic transmission ranged from 42.8% (39.8%-45.9%) to 80.6% (78.1%-83.0%). The proportion of pre-symptomatic transmission from pooled estimates was 56.4% (34.9%-78.0%). ConclusionsWhilst contact rates between symptomatic infectious and susceptible people are likely to influence the proportion of pre-symptomatic transmission, there is substantial potential for pre-symptomatic transmission of SARS-CoV-2 in a range of different contexts. Our work suggests that transmission is most likely in the day before symptom onset whereas estimates suggesting most pre-symptomatic transmission highlighted mean transmission times almost three days before symptom onset. This highlights the need for rapid case detection, contact tracing and quarantine. Strengths and weaknesses of this studyO_LIWe estimate the extent and variation of pre-symptomatic transmission of SARS-CoV-2 infection across a range of contexts. This provides important information for development and targeting of control policies and for the parameterisation of transmission models. C_LIO_LIThis is a secondary analysis using simulations based on published data, some of which is in pre-print form and not yet peer-reviewed. There is overlap in the contact tracing data that informed some of our source publications. We partially address this by summarising data at source location level as well as at study level. C_LIO_LIPopulations where symptomatic people are rapidly isolated are likely have relatively more pre-symptomatic transmission. This should be borne in mind whilst interpreting our results, but does not affect our finding that there is substantial potential for pre-symptomatic transmission of SARS-CoV-2 infection. C_LIO_LIA strength of our approach is that it builds an understanding of pre-symptomatic transmission from a range of estimates in the literature, facilitates discussion for the drivers of variation between them, and highlights the consistent message that consideration of pre-symptomatic transmission is critical for COVID-19 control policy. C_LI
ABSTRACT
ObjectivesOur objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by SARS-COV-2 virus, and provide an overview of the variation depending on the methodological approach. DesignRapid scoping review. Literature review with fixed search terms, up to 1st April 2020. Central tendency and variation of the parameter estimates for infectious period in (a) asymptomatic (b) symptomatic cases from (i) virological studies (repeated testing), (ii) tracing studies (iii) modelling studies were gathered. Narrative review of viral dynamics. Information sourcesSearch strategies developed and the following searched: PubMed, Google Scholar, MedRxiv, BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was utilised, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, HRB open databases. ResultsThere 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 pre-symptomatic 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: 10.9-15.8), 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: 15.1-21.0); 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. ConclusionsThere 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 provides a preliminary evidence base to inform models of central tendency for key parameters, and variation for exploring parameter space and sensitivity analysis. Some current models may be underestimating infectious period.
