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

  1. Jon C Emery

    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Timothy W Russell

    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Yang Liu

    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Joel Hellewell

    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Carl AB Pearson

    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. CMMID COVID-19 Working Group

  7. Gwenan M Knight

    IDE, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7263-9896
  8. Rosalind M Eggo

    Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Adam J Kucharski

    Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8814-9421
  10. Sebastian Funk

    Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2842-3406
  11. Stefan Flasche

    Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Rein M G J Houben

    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
    For correspondence
    rein.houben@lshtm.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4132-7467

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.

Reviewing Editor

  1. Marc Lipsitch, Harvard TH Chan School of Public Health, United States

Version history

  1. Received: May 8, 2020
  2. Accepted: August 23, 2020
  3. Accepted Manuscript published: August 24, 2020 (version 1)
  4. Version of Record published: September 30, 2020 (version 2)

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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  1. Jon C Emery
  2. Timothy W Russell
  3. Yang Liu
  4. Joel Hellewell
  5. Carl AB Pearson
  6. CMMID COVID-19 Working Group
  7. Gwenan M Knight
  8. Rosalind M Eggo
  9. Adam J Kucharski
  10. Sebastian Funk
  11. Stefan Flasche
  12. Rein M G J Houben
(2020)
The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship
eLife 9:e58699.
https://doi.org/10.7554/eLife.58699

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https://doi.org/10.7554/eLife.58699

Further reading

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    Yuchen Zhang, Yitang Sun ... Kaixiong Ye
    Research Article

    Background:

    Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.

    Methods:

    We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.

    Results:

    Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.

    Conclusions:

    Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.

    Funding:

    Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.