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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    2. Microbiology and Infectious Disease
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    1. Epidemiology and Global Health
    Sean V Connelly, Nicholas F Brazeau ... Jeffrey A Bailey
    Research Article

    Background:

    The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission.

    Methods:

    To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018.

    Results:

    Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes.

    Conclusions:

    Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.

    Funding:

    This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel.