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DNA Methylation Changes in COVID-19 Link to Long-Term Transcriptional Dysregulation in Airway Cells

ABSTRACT: 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 re-sampled 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 3,112 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 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 a 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.

SUBMITTER: Marey Messingschlager

PROVIDER: S-SCDT-10_1038-S44321-025-00215-5 | biostudies-other |

REPOSITORIES: biostudies-other

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