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

Title: T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses
Authors: Ogbe, A
Kronsteiner, B
Skelly, DT
Pace, M
Brown, A
Adland, E
Adair, K
Akhter, HD
Ali, M
Ali, S-E
Angyal, A
Ansari, MA
Arancibia-Carcamo, CV
Brown, H
Chinnakannan, S
Conlon, C
De Lara, C
De Silva, T
Dold, C
Dong, T
Donnison, T
Eyre, D
Flaxman, A
Fletcher, H
Gardner, J
Grist, JT
Hackstein, C-P
Jaruthamsophon, K
Jeffery, K
Lambe, T
Lee, L
Li, W
Lim, N
Matthews, PC
Mentzer, AJ
Moore, SC
Naisbitt, DJ
Ogese, M
Ogg, G
Openshaw, P
Pirmohamed, M
Pollard, AJ
Ramamurthy, N
Rongkard, P
Rowland-Jones, S
Sampson, O
Screaton, G
Sette, A
Stafford, L
Thompson, C
Thomson, PJ
Thwaites, R
Vieira, V
Weiskopf, D
Zacharopoulou, P
Chalk, J
Kerr, G
Phalora, P
Csala, A
Jones, M
Robinson, N
Brown, R
Hutchings, C
Provine, N
Ratcliff, J
Amini, A
Borak, M
Dimitriadis, S
Fordwoh, T
Horsington, B
Johnson, S
Morrow, J
Warren, Y
Wells, C
Turtle, L
Klenerman, P
Goulder, P
Frater, J
Barnes, E
Dunachie, S
Item Type: Journal Article
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.
Issue Date: 6-Apr-2021
Date of Acceptance: 15-Feb-2021
URI: http://hdl.handle.net/10044/1/92429
DOI: 10.1038/s41467-021-21856-3
ISSN: 2041-1723
Publisher: Nature Research
Start Page: 1
End Page: 14
Journal / Book Title: Nature Communications
Volume: 12
Issue: 1
Copyright Statement: © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
VIRUS
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
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
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
VIRUS
Publication Status: Published
Article Number: ARTN 2055
Online Publication Date: 2021-04-06
Appears in Collections:National Heart and Lung Institute
Imperial College London COVID-19



This item is licensed under a Creative Commons License Creative Commons