T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
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Barbara
Kronsteiner
;
Donal T
Skelly
;
Matthew
Pace
;
Anthony
Brown
;
Emily
Adland
;
Kareena
Adair
;
Hossain Delowar
Akhter
;
Mohammad
Ali
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Serat-E
Ali
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+53 more...
Adrienn
Angyal
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M Azim
Ansari
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Carolina V
Arancibia-Cárcamo
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Helen
Brown
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Senthil
Chinnakannan
;
Christopher
Conlon
;
Catherine
de Lara
;
Thushan
de Silva
;
Christina
Dold
;
Tao
Dong
;
Timothy
Donnison
;
David
Eyre
;
Amy
Flaxman
;
Helen
Fletcher
;
Joshua
Gardner
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James T
Grist
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Carl-Philipp
Hackstein
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Kanoot
Jaruthamsophon
;
Katie
Jeffery
;
Teresa
Lambe
;
Lian
Lee
;
Wenqin
Li
;
Nicholas
Lim
;
Philippa C
Matthews
;
Alexander J
Mentzer
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Shona C
Moore
;
Dean J
Naisbitt
;
Monday
Ogese
;
Graham
Ogg
;
Peter
Openshaw
;
Munir
Pirmohamed
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Andrew J
Pollard
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Narayan
Ramamurthy
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Patpong
Rongkard
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Sarah
Rowland-Jones
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Oliver
Sampson
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Gavin
Screaton
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Alessandro
Sette
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Lizzie
Stafford
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Craig
Thompson
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Paul J
Thomson
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Ryan
Thwaites
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Vinicius
Vieira
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Daniela
Weiskopf
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Panagiota
Zacharopoulou
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Oxford Immunology Network Covid-19 Response T Cell Consortium
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Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinica
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Lance
Turtle
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Paul
Klenerman
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Philip
Goulder
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John
Frater
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Eleanor
Barnes
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Susanna
Dunachie
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Oxford Immunology Network Covid-19 Response T Cell Consortium, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinica;
(2021)
T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
Nature communications, 12 (1).
2055-.
ISSN 2041-1723
DOI: 10.1038/s41467-021-21856-3
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.
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