T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
;
BarbaraKronsteiner;
Donal T Skelly ;
MatthewPace;
Anthony Brown ;
EmilyAdland;
KareenaAdair;
Hossain DelowarAkhter;
Mohammad Ali ;
Serat-EAli;
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AdriennAngyal;
M AzimAnsari;
Carolina VArancibia-Cárcamo;
HelenBrown;
Senthil Chinnakannan ;
Christopher Conlon ;
Catherinede Lara;
Thushande Silva;
ChristinaDold;
TaoDong;
Timothy Donnison ;
DavidEyre;
Amy Flaxman ;
Helen Fletcher ;
JoshuaGardner;
James TGrist;
Carl-PhilippHackstein;
Kanoot Jaruthamsophon ;
Katie Jeffery ;
Teresa Lambe ;
Lian Lee ;
WenqinLi;
NicholasLim;
Philippa C Matthews ;
Alexander J Mentzer ;
Shona C Moore ;
Dean JNaisbitt;
MondayOgese;
GrahamOgg;
Peter Openshaw ;
MunirPirmohamed;
Andrew J Pollard ;
NarayanRamamurthy;
PatpongRongkard;
SarahRowland-Jones;
Oliver Sampson ;
GavinScreaton;
AlessandroSette;
LizzieStafford;
Craig Thompson ;
Paul JThomson;
Ryan Thwaites ;
Vinicius Vieira ;
DanielaWeiskopf;
PanagiotaZacharopoulou;
Oxford Immunology Network Covid-19 Response T Cell Consortium;
Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinica;
Lance Turtle ;
Paul Klenerman ;
PhilipGoulder;
John Frater ;
Eleanor Barnes ;
Susanna Dunachie ;
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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