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Temporal multi-omics analysis of COVID-19 in end-stage kidney disease

Lookup NU author(s): Dr Emily StephensonORCiD, Dr Win Tun, Professor Muzlifah Haniffa

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2025 The Author(s). Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. We performed longitudinal single-cell immune profiling of ESKD patients with COVID-19. Transcriptome, surface proteome, and immunoreceptor sequencing data were generated on 580,040 high-quality cells, derived from 187 samples from 61 patients. For a subset of individuals, we obtained samples before and during infection, allowing intra-individual comparison. Longitudinal profiling demonstrated distinct temporal gene expression trajectories in severe/critical versus mild/moderate COVID-19. We identified a population of transcriptionally distinct monocytes that emerged in peripheral blood following glucocorticoid treatment. Evaluation of clonal T cell dynamics showed that the fastest expanding clones were enriched in known SARS-CoV-2-specific sequences and shared across multiple patients. Comparison with external datasets revealed upregulation of immune cell TGF-β pathway expression in ESKD, irrespective of COVID-19 status. Our data delineate the temporal dynamics of the immune response in COVID-19 in a high-risk population.


Publication metadata

Author(s): Stephenson E, Macdonald-Dunlop E, Dratva LM, Lindeboom RGH, Tuong ZK, Tun WM, Kretschmer L, Buang NB, Ballereau S, Cabantaus M, Penalver A, Prigmore E, Ferdinand JR, Stewart BJ, Gisby J, Malik TH, Clarke CL, Medjeral-Thomas N, Prendecki M, McAdoo S, Portet A, Willicombe M, Sandhu E, Pickering MC, Botto M, Teichmann SA, Haniffa M, Clatworthy MR, Thomas DC, Peters JE

Publication type: Article

Publication status: Published

Journal: Cell Genomics

Year: 2025

Volume: 5

Issue: 8

Print publication date: 13/08/2025

Online publication date: 17/06/2025

Acceptance date: 16/05/2025

Date deposited: 10/07/2025

ISSN (electronic): 2666-979X

Publisher: Cell Press

URL: https://doi.org/10.1016/j.xgen.2025.100918

DOI: 10.1016/j.xgen.2025.100918

Data Access Statement: De-identified patient single-cell count matrix and associated metadata are available at the COVID-19 Cell Atlas web portal as an h5ad file (on covid19cellatlas.org/index.patient.html, link for direct download at https://covid19.cog.sanger.ac.uk/eskd_covid19.h5ad). Original code has been deposited on Zenodo at https://doi.org/10.5281/zenodo.15358026. All are publicly available as of the date of publication. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.


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Funding

Funder referenceFunder name
Lister Institute of Preventive Medicine
Newcastle Biomedical Research Centre
NIHR
NIHR Imperial Biomedical Research Centre
UK Coronavirus Immunology Consortium
UKRI-DHSC COVID-19 Rapid Response Rolling Call (grant no. MR/V027638/1)
Wellcome (grant nos. 221052/Z/20/Z and 215116/Z/18/Z)
Wellcome Human Cell Atlas Strategic Science Support (grant no. WT211276/Z/18/Z)

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