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

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-21856-3

2041-1723

Ane Ogbe, Barbara Kronsteiner, Donal 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 P. Conlon, Catherine de Lara, Thushan I. 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 Jeffery, Teresa Lambe, Lian Ni Lee, Wenqin Li, Nicholas Lim, Philippa C. Matthews, Alexander J. Mentzer, Shona C. Moore, Dean J. Naisbitt, Monday O. Ogese, Graham S. 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 Thomson, Ryan S. Thwaites, Vinícius Vieira, Daniela Weiskopf, Panagiota Zacharopoulou, Jeremy Chalk, Georgina Kerr, Prabhjeet Phalora, Anna Csala, Mathew Jones, Nicola Robinson, Brent Brown, Claire Hutchings, Nicholas M. Provine, Jeremy Ratcliff, Ali Amini, Martyna Borak, Stavros Dimitriadis, Thomas Fordwoh, Bryn Horsington, Síle A. Johnson, Jordan Morrow, Yolanda Warren, Charlie Wells, Lance Turtle, Paul Klenerman, Philip Goulder, John Frater, Eleanor Barnes, Susanna Dunachie,

Long-Term Effects of COVID-19

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.