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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.

Original publication

DOI

10.1038/s41467-021-21856-3

Type

Journal article

Journal

Nat Commun

Publication Date

06/04/2021

Volume

12

Keywords

Antiviral Agents, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, COVID-19, Cell Proliferation, Cross Reactions, Cytokines, HEK293 Cells, Health Personnel, Humans, Immunoassay, Immunoglobulin G, Immunologic Memory, Interferon-gamma, Pandemics, Peptides, SARS-CoV-2, T-Lymphocytes