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-.

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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: Biodefense, Vaccine Related, Pneumonia, Infectious Diseases, Prevention, Emerging Infectious Diseases, Lung, Pneumonia & Influenza, Clinical Research, 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: 15 Mar 2024 17:20
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