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

Nature Communications, ISSN: 2041-1723, Vol: 12, Issue: 1, Page: 2055
2021
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Article Description

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.

Bibliographic Details

Ane Ogbe; Barbara Kronsteiner; Donal T. Skelly; Matthew Pace; Anthony Brown; Emily Adland; Hossain Delowar Akhter; Mohammad Ali; M. Azim Ansari; Helen Brown; Senthil Chinnakannan; Catherine de Lara; Timothy Donnison; Carl Philipp Hackstein; Lian Lee; Wenqin Li; Nicholas Lim; Philippa C. Matthews; Narayan Ramamurthy; Patpong Rongkard; Oliver Sampson; Vinicius Vieira; Panagiota Zacharopoulou; Prabhjeet Phalora; Anna Csala; Mathew Jones; Nicola Robinson; Rachael Brown; Claire Hutchings; Jeremy Ratcliff; Paul Klenerman; John Frater; Eleanor Barnes; Susanna Dunachie; Christopher Conlon; David Eyre; Katie Jeffery; Alexander J. Mentzer; Graham Ogg; Lizzie Stafford; Charlie Wells; Carolina V. Arancibia-Cárcamo; Kareena Adair; Serat E. Ali; Joshua Gardner; Kanoot Jaruthamsophon; Dean J. Naisbitt; Monday Ogese; Munir Pirmohamed; Paul J. Thomson; Adrienn Angyal; Thushan de Silva; Sarah Rowland-Jones; Martyna Borak; Bryn Horsington; Jordan Morrow; Yolanda Warren; Christina Dold; Andrew J. Pollard; James T. Grist; Tao Dong; Amy Flaxman; Teresa Lambe; Helen Fletcher; Gavin Screaton; Shona C. Moore; Lance Turtle; Peter Openshaw; Ryan Thwaites; Alessandro Sette; Daniela Weiskopf; Craig Thompson; Philip Goulder; Jeremy Chalk; Georgina Kerr; Nicholas Provine; Ali Amini; Stavros Dimitriadis; Thomas Fordwoh; Sile Johnson

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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