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

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, Carolina V. Arancibia-Cárcamo, Helen Brown, Senthil Chinnakannan, Christopher Conlon, Catherine Lara, Thushan Silva, Christina Dold, Tao Dong, Timothy Donnison, David Eyre, Amy Flaxman, Helen Fletcher, Joshua Gardner, James T. Grist, Carl-Philipp Hackstein, Kanoot Jaruthamsophon, Katie Jeffery, Teresa Lambe, Lian Lee, Wenqin Li, Nicholas Lim, Philippa C. Matthews, Alexander J. Mentzer, Shona C. Moore, Dean J. Naisbitt, Monday Ogese, Graham Ogg, Peter Openshaw, Munir Pirmohamed, Andrew J. Pollard, Narayan Ramamurthy, Patpong Rongkard, Sarah Rowland-Jones, Oliver Sampson, Gavin Screaton, Alessandro Sette, Lizzie Stafford, Craig Thompson, Paul J. Thomson, Ryan Thwaites, Vinicius Vieira, Daniela Weiskopf, Panagiota Zacharopoulou, Lance Turtle, Paul Klenerman (), Philip Goulder, John Frater, Eleanor Barnes and Susanna Dunachie
Additional contact information
Ane Ogbe: University of Oxford
Barbara Kronsteiner: University of Oxford
Donal T. Skelly: 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
Serat-E Ali: University of Liverpool
Adrienn Angyal: University of Sheffield
M. Azim Ansari: University of Oxford
Carolina V. Arancibia-Cárcamo: University of Oxford
Helen Brown: University of Oxford
Senthil Chinnakannan: University of Oxford
Christopher Conlon: University of Oxford
Catherine Lara: University of Oxford
Thushan Silva: University of Sheffield
Christina Dold: University of Oxford
Tao Dong: University of Oxford
Timothy Donnison: University of Oxford
David Eyre: Oxford University Hospitals NHS Foundation Trust
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
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
Alexander J. Mentzer: Oxford University Hospitals NHS Foundation Trust
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
Peter Openshaw: National Heart and Lung institute, Imperial College
Munir Pirmohamed: University of Liverpool
Andrew J. Pollard: University of Oxford
Narayan Ramamurthy: University of Oxford
Patpong Rongkard: University of Oxford
Sarah Rowland-Jones: University of Sheffield
Oliver Sampson: University of Oxford
Gavin Screaton: University of Oxford
Alessandro Sette: La Jolla Institute for Immunology
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
Daniela Weiskopf: La Jolla Institute for Immunology
Panagiota Zacharopoulou: University of Oxford
Lance Turtle: Veterinary and Ecological Sciences, University of Liverpool
Paul Klenerman: University of Oxford
Philip Goulder: University of Oxford
John Frater: University of Oxford
Eleanor Barnes: University of Oxford
Susanna Dunachie: University of Oxford

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21856-3

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