Severely ill COVID-19 patients display augmented functional properties in SARS-CoV-2-reactive CD8 + T cells.



Kusnadi, Anthony, Ramírez-Suástegui, Ciro, Fajardo, Vicente, Chee, Serena J, Meckiff, Benjamin J, Simon, Hayley, Pelosi, Emanuela, Seumois, Grégory, Ay, Ferhat, Vijayanand, Pandurangan
et al (show 1 more authors) (2020) Severely ill COVID-19 patients display augmented functional properties in SARS-CoV-2-reactive CD8 + T cells. bioRxiv, 1 (07-14). 2020.07.09.194027-. ISSN 2692-8205, 2692-8205

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Abstract

The molecular properties of CD8 + 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 + T cells from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8 + 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 non-exhausted subsets 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 + T cell memory responses in patients with severe COVID-19 illness. CD8 + T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features. Cells with such features were mostly absent in SARS-CoV-2 responsive 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 + T cells responding to SARS-CoV-2.

Item Type: Article
Uncontrolled Keywords: 32 Biomedical and Clinical Sciences, 3202 Clinical Sciences, Emerging Infectious Diseases, Coronaviruses Therapeutics and Interventions, Clinical Research, Coronaviruses, Lung, Cancer, Infectious Diseases, 2.1 Biological and endogenous factors, Inflammatory and immune system, Infection, 3 Good Health and Well Being
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 22 Dec 2021 09:33
Last Modified: 07 Dec 2024 11:59
DOI: 10.1101/2020.07.09.194027
Open Access URL: https://www.ncbi.nlm.nih.gov/pubmed/32676602
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3145790