ArticleClinical epigenetics2024
Cell-free DNA methylation reveals cell-specific tissue injury and correlates with disease severity and patient outcomes in COVID-19.
Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- Dalpiciclib plus endocrine therapy in women with HRNature cancer · 2026Trial
- Circulating Cell-free DNA as a biomarker for radiation-induced injury: From mechanistic insights to clinical translation.Cancer metastasis reviews · 2026Review
- DNAm landscape up to 4 months post SARS-CoV-2 infection: insights from four population-based cohorts.Clinical epigenetics · 2026Article
- MethylSense: high accuracy machine learning-based diagnostics forJournal of clinical microbiology · 2026Article
- Placental DNA methylation dysregulation underlies fetal growth restriction associated with maternal pre-pregnancy underweight.BMC pregnancy and childbirth · 2026Article
- Cell-free DNA methylation-based detection of organ damage following proton versus photon radiotherapy: a case series.Translational pediatrics · 2026Article
- Comprehensive assessment of homologous recombination deficiency via simultaneous methylation and mutation analysis in epithelial ovarian cancer: implications for PARP inhibitors efficacy.Biomarker research · 2025Article
- Epigenetic liquid biopsies reveal endothelial turnover and erythropoiesis in asymptomatic COVID-19.Life science alliance · 2025Article
- Identification of reactive CpGs and RNA expression in early COVID-19 through cis-eQTM analysis reflecting disease severity and recovery.Communications biology · 2025Article
- Circulating Cell-Free DNA in Metabolic Diseases.Journal of the Endocrine Society · 2025Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe recently identified methylation patterns specific to cell type allows the tracing of cell death dynamics at the cellular level in health and diseases. This study used COVID-19 as a disease model to investigate the efficacy of cell-specific cell-free DNA (cfDNA) methylation markers in reflecting or predicting disease severity or outcome.
methodsWhole genome methylation sequencing of cfDNA was performed for 20 healthy individuals, 20 cases with non-hospitalized COVID-19 and 12 cases with severe COVID-19 admitted to intensive care unit (ICU). Differentially methylated regions (DMRs) and gene ontology pathway enrichment analyses were performed to explore the locus-specific methylation difference between cohorts. The proportion of cfDNA derived from lung and immune cells to a given sample (i.e. tissue fraction) at cell-type resolution was estimated using a novel algorithm, which reflects lung injuries and immune response in COVID-19 patients and was further used to evaluate clinical severity and patient outcome.
resultsCOVID‑19 patients had globally reduced cfDNA methylation level compared with healthy controls. Compared with non-hospitalized COVID-19 patients, the cfDNA methylation pattern was significantly altered in severe patients with the identification of 11,156 DMRs, which were mainly enriched in pathways related to immune response. Markedly elevated levels of cfDNA derived from lung and more specifically alveolar epithelial cells, bronchial epithelial cells, and lung endothelial cells were observed in COVID-19 patients compared with healthy controls. Compared with non-hospitalized patients or healthy controls, severe COVID-19 had significantly higher cfDNA derived from B cells, T cells and granulocytes and lower cfDNA from natural killer cells. Moreover, cfDNA derived from alveolar epithelial cells had the optimal performance to differentiate COVID-19 with different severities, lung injury levels, SOFA scores and in-hospital deaths, with the area under the receiver operating characteristic curve of 0.958, 0.941, 0.919 and 0.955, respectively.
conclusionSevere COVID-19 has a distinct cfDNA methylation signature compared with non-hospitalized COVID-19 and healthy controls. Cell type-specific cfDNA methylation signature enables the tracing of COVID-19 related cell deaths in lung and immune cells at cell-type resolution, which is correlated with clinical severities and outcomes, and has extensive application prospects to evaluate tissue injuries in diseases with multi-organ dysfunction.
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