Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8<SUP>+</SUP> T cells

Kusnadi, Anthony, Ramirez-Suastegui, Ciro, Fajardo, Vicente, Chee, Serena J, Meckiff, Benjamin J, Simon, Hayley, Pelosi, Emanuela, Seumois, Gregory, Ay, Ferhat, Vijayanand, Pandurangan
et al (show 1 more authors) (2021) Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8<SUP>+</SUP> T cells. SCIENCE IMMUNOLOGY, 6 (55). eabe4782-.

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The molecular properties of CD8<sup>+</sup> T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8<sup>+</sup> T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8<sup>+</sup> T cell response to SARS-CoV-2 was 'exhausted' or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8<sup>+</sup> T cell memory responses in patients with severe COVID-19 illness. CD8<sup>+</sup> T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8<sup>+</sup> T cells responding to SARS-CoV-2.

Item Type: Article
Uncontrolled Keywords: CD8-Positive T-Lymphocytes, Humans, NF-kappa B, Signal Transduction, Immunologic Memory, Glycolysis, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Single-Cell Analysis, COVID-19, SARS-CoV-2
Depositing User: Symplectic Admin
Date Deposited: 18 Feb 2021 11:12
Last Modified: 15 Mar 2024 17:19
DOI: 10.1126/sciimmunol.abe4782
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