Circulating mitochondria! DNA is an early indicator of severe illness and mortality from COVID-19

BACKGROUND. Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined. METHODS. We measured circulating MT-DNA levels in...

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Veröffentlicht in:JCI insight 2021-02, Vol.6 (4), Article 143299
Hauptverfasser: Scozzi, Davide, Cano, Marlene, Ma, Lina, Zhou, Dequan, Zhu, Ji Hong, O'Halloran, Jane A., Goss, Charles, Rauseo, Adriana M., Liu, Zhiyi, Sahu, Sanjaya K., Peritore, Valentina, Rocco, Monica, Ricci, Alberto, Amodeo, Rachele, Aimati, Laura, Ibrahim, Mohsen, Hachem, Ramsey, Kreisel, Daniel, Mudd, Philip A., Kulkarni, Hrishikesh S., Gelman, Andrew E.
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container_issue 4
container_start_page
container_title JCI insight
container_volume 6
creator Scozzi, Davide
Cano, Marlene
Ma, Lina
Zhou, Dequan
Zhu, Ji Hong
O'Halloran, Jane A.
Goss, Charles
Rauseo, Adriana M.
Liu, Zhiyi
Sahu, Sanjaya K.
Peritore, Valentina
Rocco, Monica
Ricci, Alberto
Amodeo, Rachele
Aimati, Laura
Ibrahim, Mohsen
Hachem, Ramsey
Kreisel, Daniel
Mudd, Philip A.
Kulkarni, Hrishikesh S.
Gelman, Andrew E.
description BACKGROUND. Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined. METHODS. We measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19. RESULTS. Circulating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy. CONCLUSION. These results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.
doi_str_mv 10.1172/jci.insight.143299
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DNA is an early indicator of severe illness and mortality from COVID-19</title><source>DOAJ Directory of Open Access Journals</source><source>Web of Science - Science Citation Index Expanded - 2021&lt;img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /&gt;</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Scozzi, Davide ; Cano, Marlene ; Ma, Lina ; Zhou, Dequan ; Zhu, Ji Hong ; O'Halloran, Jane A. ; Goss, Charles ; Rauseo, Adriana M. ; Liu, Zhiyi ; Sahu, Sanjaya K. ; Peritore, Valentina ; Rocco, Monica ; Ricci, Alberto ; Amodeo, Rachele ; Aimati, Laura ; Ibrahim, Mohsen ; Hachem, Ramsey ; Kreisel, Daniel ; Mudd, Philip A. ; Kulkarni, Hrishikesh S. ; Gelman, Andrew E.</creator><creatorcontrib>Scozzi, Davide ; Cano, Marlene ; Ma, Lina ; Zhou, Dequan ; Zhu, Ji Hong ; O'Halloran, Jane A. ; Goss, Charles ; Rauseo, Adriana M. ; Liu, Zhiyi ; Sahu, Sanjaya K. ; Peritore, Valentina ; Rocco, Monica ; Ricci, Alberto ; Amodeo, Rachele ; Aimati, Laura ; Ibrahim, Mohsen ; Hachem, Ramsey ; Kreisel, Daniel ; Mudd, Philip A. ; Kulkarni, Hrishikesh S. ; Gelman, Andrew E.</creatorcontrib><description>BACKGROUND. Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined. METHODS. We measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19. RESULTS. Circulating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy. CONCLUSION. 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subjects Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
Science & Technology
title Circulating mitochondria! DNA is an early indicator of severe illness and mortality from COVID-19
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