The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship
Abstract
A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.
Data availability
All data analysed during this study are included in the manuscript and supporting files. Model code is available through github.
Article and author information
Author details
Funding
European Research Council Starting Grant (Action Number 757699)
- Jon C Emery
- Rein M G J Houben
Wellcome (206250/Z/17/Z)
- Timothy W Russell
- Adam J Kucharski
Wellcome (208812/Z/17/Z)
- Stefan Flasche
Wellcome (210758/Z/18/Z)
- Joel Hellewell
- Sebastian Funk
Bill and Melinda Gates Foundation (INV-003174)
- Yang Liu
Bill and Melinda Gates Foundation (NTD Modelling Consortium OPP1184344)
- Carl AB Pearson
DFID/Wellcome Trust (Epidemic Preparedness Coronavirus research programme 221303/Z/20/Z)
- Carl AB Pearson
European Union Horizon 2020 (project EpiPose (101003688))
- Yang Liu
HDR UK (MR/S003975/1)
- Rosalind M Eggo
National Institute for Health Research (16/137/109)
- Yang Liu
Medical Research Council (MC_PC 19065)
- Rosalind M Eggo
Medical Research Council (MR/P014658/1)
- Gwenan M Knight
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Emery et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Background:
The role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD).
Methods:
Untargeted metabolomics was performed on serum samples of 5004 children aged 6–59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children’s milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥1. The interaction between significant metabolites and the child’s age was tested.
Results:
Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child’s nutritional status, diet quality, and infant age. Cresol sulfate (β=–0.07; adjusted-p <0.001), hippuric acid (β=–0.06; adjusted-p <0.001), phenylacetylglutamine (β=–0.06; adjusted-p <0.001), and trimethylamine-N-oxide (β=–0.05; adjusted-p=0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged –1 SD: β=–0.05; pP=0.01;+1 SD: β=0.05; p=0.02) and methylhistidine (–1 SD: β = - 0.04; p=0.04;+1 SD: β=0.04; p=0.03).
Conclusions:
Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding:
Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.