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


Nature Communications

Contributing to research themes:


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.

Author list:

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-Carcamo, Helen Brown, Senthil Chinnakannan, Christopher P Conlon, Catherine de Lara, Thushan de Silva, Christina Dold, Tao Dong, Timothy Donnison, David W Eyre, Amy Flaxman, Helen A Fletcher, Joshua Gardner, James T Grist, Carl-Philipp Hackstein, Kanoot Jaruthamsophon, Katie Jeffrey, 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 L Sampson, Gavin Screaton, Alessandro Sette, Lizzie Stafford, Craig Thompson, Paul J Thomson, Ryan Thwaites, Vinicius Vieira, Daniela Weiskopf, Panagiota Zacharopoulou, Oxford Immunology Network Covid-19 Response T cell Consortium, Oxford Protective T cell Immunology for COVID-19 (OPTIC) Clinical team, Lance Turtle, Paul Klenerman, Philip Goulder, John Frater, Eleanor Barnes, Susanna Dunachie