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