ArticleJCI insight2021
Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
101 citing papers in PubMed, 3 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- Systemic cytokines drive conserved severity-associated myeloid responses across bacterial and viral infections.Communications biology · 2025Pooled it
- Circulating free DNA as a diagnostic marker for echinococcosis: a systematic review and meta-analysis.Frontiers in microbiology · 2024Pooled it
- Cell-free DNA as diagnostic and prognostic biomarkers for adult sepsis: a systematic review and meta-analysis.Scientific reports · 2023Pooled it
- Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.The Journal of clinical investigation · 2024Trial
- Expanding role of cell-free DNA for the early diagnosis and monitoring of pulmonary diseases.Chinese medical journal · 2026Review
- Cell-free nucleic acids as a non-invasive biomarker for predicting COVID-19 disease severity and outcome: a retrospective cohort study.BMC infectious diseases · 2026Article
- Early post-transplant recipient tissue injury predicts allograft function, rejection and survival in lung transplant recipients: evidence from cell-free DNA.The European respiratory journal · 2026Article
- Activation and Cell Death of Mouse Eosinophils in Response to Different Microenvironmental Stimuli.Cells · 2026Article
- Deep Biological Clocks in Critical Care Medicine: A Scoping Review Toward Translational Precision Care.Journal of personalized medicine · 2026Review
- Cell-Free DNA Profiles End-Organ Injury and Predicts Outcomes in Advanced Heart Failure With Left Ventricular Assist Device Implantation.Circulation. Heart failure · 2026Observational
- Circulating cell-free mitochondrial DNA as a candidate marker of hyperinflammation and immune activation in pre-adolescents, adolescents and young adults with COVID-19 and comorbidities.Revista do Instituto de Medicina Tropical de Sao Paulo · 2026Article
- Plasma Cell-free DNA Associated With Risk of Mortality and Chronic Lung Allograft Dysfunction Among Lung Transplant Recipients WithTransplantation direct · 2026Article
- Quantifying endothelial damage by digital droplet polymerase chain reaction (PCR) of endothelial cell-free DNA in COVID-19 patients.Research and practice in thrombosis and haemostasis · 2026Article
- CfDNA as a surrogate marker for COVID-19 severity in patients with influenza-like symptoms with and without SARS-CoV-2 infection in general practice: a prospective cohort study.Virology journal · 2025Article
- Whole-genome profiling of age- and sex-associated DNA methylation signatures in human plasma cell-free DNA.Communications medicine · 2025Article
- Tracing the tissue origin of cell-free DNA through open chromatin footprint.Communications biology · 2025Article
- Article
- Epigenetic liquid biopsies reveal endothelial turnover and erythropoiesis in asymptomatic COVID-19.Life science alliance · 2025Article
- Extracellular DNA, hyaluronic acid, HIF pathways, and LncRNAs as predictive biomarkers of severe COVID-19.Virology journal · 2025Review
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
INTRODUCTIONThe clinical course of coronavirus 2019 (COVID-19) is heterogeneous, ranging from mild to severe multiorgan failure and death. In this study, we analyzed cell-free DNA (cfDNA) as a biomarker of injury to define the sources of tissue injury that contribute to such different trajectories.METHODSWe conducted a multicenter prospective cohort study to enroll patients with COVID-19 and collect plasma samples. Plasma cfDNA was subject to bisulfite sequencing. A library of tissue-specific DNA methylation signatures was used to analyze sequence reads to quantitate cfDNA from different tissue types. We then determined the correlation of tissue-specific cfDNA measures to COVID-19 outcomes. Similar analyses were performed for healthy controls and a comparator group of patients with respiratory syncytial virus and influenza.RESULTSWe found markedly elevated levels and divergent tissue sources of cfDNA in COVID-19 patients compared with patients who had influenza and/or respiratory syncytial virus and with healthy controls. The major sources of cfDNA in COVID-19 were hematopoietic cells, vascular endothelium, hepatocytes, adipocytes, kidney, heart, and lung. cfDNA levels positively correlated with COVID-19 disease severity, C-reactive protein, and D-dimer. cfDNA profile at admission identified patients who subsequently required intensive care or died during hospitalization. Furthermore, the increased cfDNA in COVID-19 patients generated excessive mitochondrial ROS (mtROS) in renal tubular cells in a concentration-dependent manner. This mtROS production was inhibited by a TLR9-specific antagonist.CONCLUSIONcfDNA maps tissue injury that predicts COVID-19 outcomes and may mechanistically propagate COVID-19-induced tissue injury.FUNDINGIntramural Targeted Anti-COVID-19 grant, NIH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.