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10.1172/jci.insight.147610

http://scihub22266oqcxt.onion/10.1172/jci.insight.147610
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suck abstract from ncbi


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pmid33651717      JCI+Insight 2021 ; 6 (7): ä
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  • Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury #MMPMID33651717
  • Andargie TE; Tsuji N; Seifuddin F; Jang MK; Yuen PS; Kong H; Tunc I; Singh K; Charya A; Wilkins K; Nathan S; Cox A; Pirooznia M; Star RA; Agbor-Enoh S
  • JCI Insight 2021[Apr]; 6 (7): ä PMID33651717show ga
  • 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.
  • |*COVID-19/blood/complications/diagnosis/mortality[MESH]
  • |*Cell-Free Nucleic Acids/analysis/blood[MESH]
  • |*Multiple Organ Failure/blood/diagnosis/etiology[MESH]
  • |*SARS-CoV-2/isolation & purification/pathogenicity[MESH]
  • |Biomarkers/analysis/blood[MESH]
  • |Cohort Studies[MESH]
  • |DNA Methylation[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Organ Specificity/*genetics[MESH]
  • |Outcome Assessment, Health Care[MESH]
  • |Prognosis[MESH]
  • |Prospective Studies[MESH]
  • |Reproducibility of Results[MESH]
  • |Severity of Illness Index[MESH]


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