1. Epidemiology and Global Health
Download icon

High infectiousness immediately before COVID-19 symptom onset highlights the importance of continued contact tracing

  1. William Stephen Hart  Is a corresponding author
  2. Philip K Maini
  3. Robin N Thompson
  1. University of Oxford, United Kingdom
  2. University of Warwick, United Kingdom
Short Report
  • Cited 1
  • Views 967
  • Annotations
Cite this article as: eLife 2021;10:e65534 doi: 10.7554/eLife.65534


Background: Understanding changes in infectiousness during SARS-COV-2 infections is critical to assess the effectiveness of public health measures such as contact tracing.

Methods: Here, we develop a novel mechanistic approach to infer the infectiousness profile of SARS-COV-2 infected individuals using data from known infector-infectee pairs. We compare estimates of key epidemiological quantities generated using our mechanistic method with analogous estimates generated using previous approaches.

Results: The mechanistic method provides an improved fit to data from SARS-CoV-2 infector-infectee pairs compared to commonly used approaches. Our best-fitting model indicates a high proportion of presymptomatic transmissions, with many transmissions occurring shortly before the infector develops symptoms.

Conclusions: High infectiousness immediately prior to symptom onset highlights the importance of continued contact tracing until effective vaccines have been distributed widely, even if contacts from a short time window before symptom onset alone are traced.

Funding: Engineering and Physical Sciences Research Council (EPSRC).

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. A source data file has been provided for Figure 2, containing the SARS-CoV-2 transmission pair data used in our analyses. These data were originally reported in references (3,10,29-31), and the combined data were also considered in reference (4). Code for reproducing our results is available at https://github.com/will-s-hart/COVID-19-Infectiousness-Profile.

Article and author information

Author details

  1. William Stephen Hart

    Mathematical Institute, University of Oxford, Oxford, United Kingdom
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2504-6860
  2. Philip K Maini

    Mathematical Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Robin N Thompson

    Mathematics Institute, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.


Engineering and Physical Sciences Research Council (Excellence Award)

  • William Stephen Hart

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jennifer Flegg, The University of Melbourne, Australia

Publication history

  1. Received: December 7, 2020
  2. Accepted: April 25, 2021
  3. Accepted Manuscript published: April 26, 2021 (version 1)
  4. Version of Record published: June 11, 2021 (version 2)


© 2021, Hart 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.


  • 967
    Page views
  • 154
  • 1

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Ecology
    2. Epidemiology and Global Health
    Morgan P Kain et al.
    Research Article Updated

    Identifying the key vector and host species that drive the transmission of zoonotic pathogens is notoriously difficult but critical for disease control. We present a nested approach for quantifying the importance of host and vectors that integrates species’ physiological competence with their ecological traits. We apply this framework to a medically important arbovirus, Ross River virus (RRV), in Brisbane, Australia. We find that vertebrate hosts with high physiological competence are not the most important for community transmission; interactions between hosts and vectors largely underpin the importance of host species. For vectors, physiological competence is highly important. Our results identify primary and secondary vectors of RRV and suggest two potential transmission cycles in Brisbane: an enzootic cycle involving birds and an urban cycle involving humans. The framework accounts for uncertainty from each fitted statistical model in estimates of species’ contributions to transmission and has has direct application to other zoonotic pathogens.

    1. Epidemiology and Global Health
    2. Genetics and Genomics
    Mohd Anisul et al.
    Research Article Updated


    The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19.


    To identify host proteins that may contribute to the risk of severe COVID-19, we undertook proteome-wide genetic colocalisation tests, and polygenic (pan) and cis-Mendelian randomisation analyses leveraging publicly available protein and COVID-19 datasets.


    Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble Fas (colocalisation probability >0.9, p=1 × 10-4), implicating Fas-mediated apoptosis as a potential target for COVID-19 risk. The polygenic (pan) and cis-Mendelian randomisation analyses showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal is highly pleiotropic, and a look-up of proteins associated with the ABO signal revealed that the strongest association was with soluble CD209. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19.


    Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19.


    MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/4). JSh and GJW were funded by the Wellcome Trust Grant 206194. This research was funded in part by the Wellcome Trust [Grant 206194]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.