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



Ogbe, Ane, Kronsteiner, Barbara, Skelly, Donal T, Pace, Matthew, Brown, Anthony, Adland, Emily, Adair, Kareena ORCID: 0000-0001-9884-2094, Akhter, Hossain Delowar, Ali, Mohammad, Ali, Serat-E ORCID: 0000-0002-9806-8796
et al (show 70 more authors) (2021) T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses. NATURE COMMUNICATIONS, 12 (1). 2055-.

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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.

Item Type: Article
Uncontrolled Keywords: Oxford Immunology Network Covid-19 Response T Cell Consortium, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team, T-Lymphocytes, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Humans, Peptides, Immunoglobulin G, Cytokines, Antiviral Agents, Immunoassay, Cell Proliferation, Cross Reactions, Immunologic Memory, Health Personnel, Interferon-gamma, HEK293 Cells, Pandemics, COVID-19, SARS-CoV-2
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 04 Jun 2021 11:57
Last Modified: 18 Jan 2023 22:36
DOI: 10.1038/s41467-021-21856-3
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3125113