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Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality

Several predictive biomarkers for coronavirus disease (COVID-19)-associated mortality in critically ill patients have been described. Although mitochondrial DNA (mtDNA) is elevated in patients with COVID-19, the association with coagulation function and its predictive power for mortality is unclear....

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Autores principales: Edinger, Fabian, Edinger, Sophia, Koch, Christian, Markmann, Melanie, Hecker, Matthias, Sander, Michael, Schneck, Emmanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740249/
https://www.ncbi.nlm.nih.gov/pubmed/36498735
http://dx.doi.org/10.3390/jcm11237161
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author Edinger, Fabian
Edinger, Sophia
Koch, Christian
Markmann, Melanie
Hecker, Matthias
Sander, Michael
Schneck, Emmanuel
author_facet Edinger, Fabian
Edinger, Sophia
Koch, Christian
Markmann, Melanie
Hecker, Matthias
Sander, Michael
Schneck, Emmanuel
author_sort Edinger, Fabian
collection PubMed
description Several predictive biomarkers for coronavirus disease (COVID-19)-associated mortality in critically ill patients have been described. Although mitochondrial DNA (mtDNA) is elevated in patients with COVID-19, the association with coagulation function and its predictive power for mortality is unclear. Accordingly, this study investigates the predictive power of mtDNA for in-hospital mortality in critically ill patients with COVID-19, and whether combining it with thromboelastographic parameters can increase its predictive performance. This prospective explorative study included 29 patients with COVID-19 and 29 healthy matched controls. mtDNA encoding for NADH dehydrogenase 1 (ND1) was quantified using a quantitative polymerase chain reaction analysis, while coagulation function was evaluated using thromboelastometry and impedance aggregometry. Receiver operating characteristic (ROC) curves were used for the prediction of in-hospital mortality. Within the first 24 h, the plasma levels of mtDNA peaked significantly (controls: 65 (28–119) copies/µL; patients: 281 (110–805) at t(0), 403 (168–1937) at t(24), and 467 (188–952) copies/µL at t(72); controls vs. patients: p = 0.02 at t(0), p = 0.03 at t(24), and p = 0.44 at t(72)). The mtDNA levels at t(24) showed an excellent predictive performance for in-hospital mortality (area under the ROC curve: 0.90 (0.75–0.90)), which could not be improved by the combination with thromboelastometric or aggregometric parameters. Critically ill patients with COVID-19 present an early increase in the plasma levels of ND1 mtDNA, lasting over 24 h. They also show impairments in platelet function and fibrinolysis, as well as hypercoagulability, but these do not correlate with the plasma levels of fibrinogen. The peak plasma levels of mtDNA can be used as a predictive biomarker for in-hospital mortality; however, the combination with coagulation parameters does not improve the predictive validity.
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spelling pubmed-97402492022-12-11 Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality Edinger, Fabian Edinger, Sophia Koch, Christian Markmann, Melanie Hecker, Matthias Sander, Michael Schneck, Emmanuel J Clin Med Article Several predictive biomarkers for coronavirus disease (COVID-19)-associated mortality in critically ill patients have been described. Although mitochondrial DNA (mtDNA) is elevated in patients with COVID-19, the association with coagulation function and its predictive power for mortality is unclear. Accordingly, this study investigates the predictive power of mtDNA for in-hospital mortality in critically ill patients with COVID-19, and whether combining it with thromboelastographic parameters can increase its predictive performance. This prospective explorative study included 29 patients with COVID-19 and 29 healthy matched controls. mtDNA encoding for NADH dehydrogenase 1 (ND1) was quantified using a quantitative polymerase chain reaction analysis, while coagulation function was evaluated using thromboelastometry and impedance aggregometry. Receiver operating characteristic (ROC) curves were used for the prediction of in-hospital mortality. Within the first 24 h, the plasma levels of mtDNA peaked significantly (controls: 65 (28–119) copies/µL; patients: 281 (110–805) at t(0), 403 (168–1937) at t(24), and 467 (188–952) copies/µL at t(72); controls vs. patients: p = 0.02 at t(0), p = 0.03 at t(24), and p = 0.44 at t(72)). The mtDNA levels at t(24) showed an excellent predictive performance for in-hospital mortality (area under the ROC curve: 0.90 (0.75–0.90)), which could not be improved by the combination with thromboelastometric or aggregometric parameters. Critically ill patients with COVID-19 present an early increase in the plasma levels of ND1 mtDNA, lasting over 24 h. They also show impairments in platelet function and fibrinolysis, as well as hypercoagulability, but these do not correlate with the plasma levels of fibrinogen. The peak plasma levels of mtDNA can be used as a predictive biomarker for in-hospital mortality; however, the combination with coagulation parameters does not improve the predictive validity. MDPI 2022-12-01 /pmc/articles/PMC9740249/ /pubmed/36498735 http://dx.doi.org/10.3390/jcm11237161 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Edinger, Fabian
Edinger, Sophia
Koch, Christian
Markmann, Melanie
Hecker, Matthias
Sander, Michael
Schneck, Emmanuel
Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality
title Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality
title_full Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality
title_fullStr Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality
title_full_unstemmed Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality
title_short Peak Plasma Levels of mtDNA Serve as a Predictive Biomarker for COVID-19 in-Hospital Mortality
title_sort peak plasma levels of mtdna serve as a predictive biomarker for covid-19 in-hospital mortality
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740249/
https://www.ncbi.nlm.nih.gov/pubmed/36498735
http://dx.doi.org/10.3390/jcm11237161
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