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DNA methylation changes during acute COVID-19 are associated with long-term transcriptional dysregulation in patients' airway epithelial cells

Molecular changes underlying the persistent health effects after SARS-CoV-2 infection remain poorly understood. To discern the gene regulatory landscape in the upper respiratory tract of COVID-19 patients, we performed enzymatic DNA methylome and single-cell RNA sequencing in nasal cells of COVID-19...

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Main Authors: Messingschlager, Marey (Author) , Mackowiak, Sebastian D. (Author) , Voelker, Maria Theresa (Author) , Bieg, Matthias (Author) , Loske, Jennifer (Author) , Chua, Robert Lorenz (Author) , Liebig, Johannes (Author) , Lukassen, Sören (Author) , Thürmann, Loreen (Author) , Seegebarth, Anke (Author) , Twardziok, Sven (Author) , Dončević, Daria (Author) , Herrmann, Carl (Author) , Lorenz, Stephan (Author) , Klages, Sven (Author) , Steinbeis, Fridolin (Author) , Witzenrath, Martin (Author) , Kurth, Florian (Author) , Conrad, Christian (Author) , Sander, Leif E. (Author) , Ishaque, Naveed (Author) , Eils, Roland (Author) , Lehmann, Irina (Author) , Laudi, Sven (Author) , Trump, Saskia (Author)
Format: Article (Journal)
Language:English
Published: 21 March 2025
In: EMBO molecular medicine
Year: 2025, Volume: 17, Issue: 5, Pages: 923-937
ISSN:1757-4684
DOI:10.1038/s44321-025-00215-5
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44321-025-00215-5
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Author Notes:Marey Messingschlager, Sebastian D. Mackowiak, Maria Theresa Voelker, Matthias Bieg, Jennifer Loske, Robert Lorenz Chua, Johannes Liebig, Sören Lukassen, Loreen Thürmann, Anke Seegebarth, Sven Twardziok, Daria Doncevic, Carl Herrmann, Stephan Lorenz, Sven Klages, Fridolin Steinbeis, Martin Witzenrath, Florian Kurth, Christian Conrad, Leif E. Sander, Naveed Ishaque, Roland Eils, Irina Lehmann, Sven Laudi, Saskia Trump
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Summary:Molecular changes underlying the persistent health effects after SARS-CoV-2 infection remain poorly understood. To discern the gene regulatory landscape in the upper respiratory tract of COVID-19 patients, we performed enzymatic DNA methylome and single-cell RNA sequencing in nasal cells of COVID-19 patients (n = 19, scRNA-seq n = 14) and controls (n = 14, scRNA-seq n = 10). In addition, we resampled a subset of these patients for transcriptome analyses at 3 (n = 7) and 12 months (n = 5) post infection and followed the expression of differentially regulated genes over time. Genome-wide DNA methylation analysis revealed 3112 differentially methylated regions between COVID-19 patients and controls. Hypomethylated regions affected immune regulatory genes, while hypermethylated regions were associated with genes governing ciliary function. These genes were not only downregulated in the acute phase of the disease but sustained repressed up to 12 months post infection in ciliated cells. Validation in an independent cohort collected 6 months post infection (n  = 15) indicated symptom-dependent transcriptional repression of ciliary genes. We therefore propose that hypermethylation observed in the acute phase may exert a long-term effect on gene expression, possibly contributing to post-acute COVID-19 sequelae.
Item Description:Gesehen am 24.02.2026
Physical Description:Online Resource
ISSN:1757-4684
DOI:10.1038/s44321-025-00215-5

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