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T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Author

Listed:
  • Ane Ogbe

    (University of Oxford)

  • Barbara Kronsteiner

    (University of Oxford
    University of Oxford)

  • Donal T. Skelly

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust
    University of Oxford)

  • Matthew Pace

    (University of Oxford)

  • Anthony Brown

    (University of Oxford)

  • Emily Adland

    (University of Oxford)

  • Kareena Adair

    (University of Liverpool)

  • Hossain Delowar Akhter

    (University of Oxford)

  • Mohammad Ali

    (University of Oxford
    University of Oxford)

  • Serat-E Ali

    (University of Liverpool)

  • Adrienn Angyal

    (University of Sheffield)

  • M. Azim Ansari

    (University of Oxford)

  • Carolina V. Arancibia-Cárcamo

    (University of Oxford
    University of Oxford)

  • Helen Brown

    (University of Oxford)

  • Senthil Chinnakannan

    (University of Oxford)

  • Christopher Conlon

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

  • Catherine Lara

    (University of Oxford)

  • Thushan Silva

    (University of Sheffield)

  • Christina Dold

    (University of Oxford
    University of Oxford)

  • Tao Dong

    (University of Oxford
    Chinese Academy of Medical Science Oxford Institute (COI), University of Oxford)

  • Timothy Donnison

    (University of Oxford)

  • David Eyre

    (Oxford University Hospitals NHS Foundation Trust
    University of Oxford)

  • Amy Flaxman

    (Jenner Institute, University of Oxford)

  • Helen Fletcher

    (London School of Hygiene and Tropical Medicine)

  • Joshua Gardner

    (University of Liverpool)

  • James T. Grist

    (University of Oxford
    University of Oxford
    University of Birmingham)

  • Carl-Philipp Hackstein

    (University of Oxford)

  • Kanoot Jaruthamsophon

    (University of Liverpool)

  • Katie Jeffery

    (Oxford University Hospitals NHS Foundation Trust)

  • Teresa Lambe

    (Jenner Institute, University of Oxford)

  • Lian Lee

    (University of Oxford)

  • Wenqin Li

    (University of Oxford)

  • Nicholas Lim

    (University of Oxford)

  • Philippa C. Matthews

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

  • Alexander J. Mentzer

    (Oxford University Hospitals NHS Foundation Trust
    University of Oxford)

  • Shona C. Moore

    (Veterinary and Ecological Sciences, University of Liverpool)

  • Dean J. Naisbitt

    (University of Liverpool)

  • Monday Ogese

    (University of Liverpool)

  • Graham Ogg

    (Oxford University Hospitals NHS Foundation Trust
    University of Oxford
    University of Oxford)

  • Peter Openshaw

    (National Heart and Lung institute, Imperial College)

  • Munir Pirmohamed

    (University of Liverpool)

  • Andrew J. Pollard

    (University of Oxford
    University of Oxford)

  • Narayan Ramamurthy

    (University of Oxford)

  • Patpong Rongkard

    (University of Oxford
    University of Oxford
    Mahidol-Oxford Tropical Medicine Research Unit)

  • Sarah Rowland-Jones

    (University of Sheffield
    University of Oxford)

  • Oliver Sampson

    (University of Oxford)

  • Gavin Screaton

    (University of Oxford)

  • Alessandro Sette

    (La Jolla Institute for Immunology
    University of California)

  • Lizzie Stafford

    (Oxford University Hospitals NHS Foundation Trust)

  • Craig Thompson

    (University of Oxford)

  • Paul J. Thomson

    (University of Liverpool)

  • Ryan Thwaites

    (National Heart and Lung institute, Imperial College)

  • Vinicius Vieira

    (University of Oxford
    University of Oxford)

  • Daniela Weiskopf

    (La Jolla Institute for Immunology
    University of California)

  • Panagiota Zacharopoulou

    (University of Oxford)

  • Lance Turtle

    (Veterinary and Ecological Sciences, University of Liverpool
    Liverpool University Hospitals NHS Foundation Trust, Member of Liverpool Health Partners)

  • Paul Klenerman

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust
    University of Oxford
    University of Oxford)

  • Philip Goulder

    (University of Oxford)

  • John Frater

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust
    University of Oxford)

  • Eleanor Barnes

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust
    University of Oxford)

  • Susanna Dunachie

    (University of Oxford
    University of Oxford
    Oxford University Hospitals NHS Foundation Trust
    University of Oxford)

Abstract

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.

Suggested Citation

  • Ane Ogbe & Barbara Kronsteiner & Donal T. Skelly & Matthew Pace & Anthony Brown & Emily Adland & Kareena Adair & Hossain Delowar Akhter & Mohammad Ali & Serat-E Ali & Adrienn Angyal & M. Azim Ansari &, 2021. "T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21856-3
    DOI: 10.1038/s41467-021-21856-3
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