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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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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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.</description><identifier>EISSN: 2379-3708</identifier><identifier>DOI: 10.1172/jci.insight.143299</identifier><identifier>PMID: 33444289</identifier><language>eng</language><publisher>ANN ARBOR: Amer Soc Clinical Investigation Inc</publisher><subject>Life Sciences & Biomedicine ; Medicine, Research & Experimental ; Research & Experimental Medicine ; Science & Technology</subject><ispartof>JCI insight, 2021-02, Vol.6 (4), Article 143299</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>87</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000621657700017</woscitedreferencesoriginalsourcerecordid><cites>FETCH-webofscience_primary_0006216577000173</cites><orcidid>0000-0001-8380-3607</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,866,2116,27931,27932,39265</link.rule.ids></links><search><creatorcontrib>Scozzi, Davide</creatorcontrib><creatorcontrib>Cano, Marlene</creatorcontrib><creatorcontrib>Ma, Lina</creatorcontrib><creatorcontrib>Zhou, Dequan</creatorcontrib><creatorcontrib>Zhu, Ji Hong</creatorcontrib><creatorcontrib>O'Halloran, Jane A.</creatorcontrib><creatorcontrib>Goss, Charles</creatorcontrib><creatorcontrib>Rauseo, Adriana M.</creatorcontrib><creatorcontrib>Liu, Zhiyi</creatorcontrib><creatorcontrib>Sahu, Sanjaya K.</creatorcontrib><creatorcontrib>Peritore, Valentina</creatorcontrib><creatorcontrib>Rocco, Monica</creatorcontrib><creatorcontrib>Ricci, Alberto</creatorcontrib><creatorcontrib>Amodeo, Rachele</creatorcontrib><creatorcontrib>Aimati, Laura</creatorcontrib><creatorcontrib>Ibrahim, Mohsen</creatorcontrib><creatorcontrib>Hachem, Ramsey</creatorcontrib><creatorcontrib>Kreisel, Daniel</creatorcontrib><creatorcontrib>Mudd, Philip A.</creatorcontrib><creatorcontrib>Kulkarni, Hrishikesh S.</creatorcontrib><creatorcontrib>Gelman, Andrew E.</creatorcontrib><title>Circulating mitochondria! DNA is an early indicator of severe illness and mortality from COVID-19</title><title>JCI insight</title><addtitle>JCI INSIGHT</addtitle><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.</description><subject>Life Sciences & Biomedicine</subject><subject>Medicine, Research & Experimental</subject><subject>Research & Experimental Medicine</subject><subject>Science & Technology</subject><issn>2379-3708</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><recordid>eNqVz71OwzAYhWELCdEKegNMHzNK8F_reEQuCBZYEGtlHKf9KsdGtgvK3VMQFwDTWZ7hPYRcMtoypvjN3mGLseB2V1smBdf6hMy5ULoRinYzsihlTyllSnK67M7ITAgpJe_0nFiD2R2CrRi3MGJNbpdin9FewfrpFrCAjeBtDhNg7NHZmjKkAYr_8NkDhhB9-UY9jClXG7BOMOQ0gnl-fVw3TF-Q08GG4he_e06u7-9ezEPz6d_SUBz66PzmPeNo87Q5Zq44Wy2V-gkW_9Xd37XBerydokmHWMUXD29kCg</recordid><startdate>20210222</startdate><enddate>20210222</enddate><creator>Scozzi, Davide</creator><creator>Cano, Marlene</creator><creator>Ma, Lina</creator><creator>Zhou, Dequan</creator><creator>Zhu, Ji Hong</creator><creator>O'Halloran, Jane A.</creator><creator>Goss, Charles</creator><creator>Rauseo, Adriana M.</creator><creator>Liu, Zhiyi</creator><creator>Sahu, Sanjaya K.</creator><creator>Peritore, Valentina</creator><creator>Rocco, Monica</creator><creator>Ricci, Alberto</creator><creator>Amodeo, Rachele</creator><creator>Aimati, Laura</creator><creator>Ibrahim, Mohsen</creator><creator>Hachem, Ramsey</creator><creator>Kreisel, Daniel</creator><creator>Mudd, Philip A.</creator><creator>Kulkarni, Hrishikesh S.</creator><creator>Gelman, Andrew E.</creator><general>Amer Soc Clinical Investigation Inc</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><orcidid>https://orcid.org/0000-0001-8380-3607</orcidid></search><sort><creationdate>20210222</creationdate><title>Circulating mitochondria! DNA is an early indicator of severe illness and mortality from COVID-19</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-webofscience_primary_0006216577000173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Life Sciences & Biomedicine</topic><topic>Medicine, Research & Experimental</topic><topic>Research & Experimental Medicine</topic><topic>Science & Technology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scozzi, Davide</creatorcontrib><creatorcontrib>Cano, Marlene</creatorcontrib><creatorcontrib>Ma, Lina</creatorcontrib><creatorcontrib>Zhou, Dequan</creatorcontrib><creatorcontrib>Zhu, Ji Hong</creatorcontrib><creatorcontrib>O'Halloran, Jane A.</creatorcontrib><creatorcontrib>Goss, Charles</creatorcontrib><creatorcontrib>Rauseo, Adriana M.</creatorcontrib><creatorcontrib>Liu, Zhiyi</creatorcontrib><creatorcontrib>Sahu, Sanjaya K.</creatorcontrib><creatorcontrib>Peritore, Valentina</creatorcontrib><creatorcontrib>Rocco, Monica</creatorcontrib><creatorcontrib>Ricci, Alberto</creatorcontrib><creatorcontrib>Amodeo, Rachele</creatorcontrib><creatorcontrib>Aimati, Laura</creatorcontrib><creatorcontrib>Ibrahim, Mohsen</creatorcontrib><creatorcontrib>Hachem, Ramsey</creatorcontrib><creatorcontrib>Kreisel, Daniel</creatorcontrib><creatorcontrib>Mudd, Philip A.</creatorcontrib><creatorcontrib>Kulkarni, Hrishikesh S.</creatorcontrib><creatorcontrib>Gelman, Andrew E.</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><jtitle>JCI insight</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scozzi, Davide</au><au>Cano, Marlene</au><au>Ma, Lina</au><au>Zhou, Dequan</au><au>Zhu, Ji Hong</au><au>O'Halloran, Jane A.</au><au>Goss, Charles</au><au>Rauseo, Adriana M.</au><au>Liu, Zhiyi</au><au>Sahu, Sanjaya K.</au><au>Peritore, Valentina</au><au>Rocco, Monica</au><au>Ricci, Alberto</au><au>Amodeo, Rachele</au><au>Aimati, Laura</au><au>Ibrahim, Mohsen</au><au>Hachem, Ramsey</au><au>Kreisel, Daniel</au><au>Mudd, Philip A.</au><au>Kulkarni, Hrishikesh S.</au><au>Gelman, Andrew E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating mitochondria! DNA is an early indicator of severe illness and mortality from COVID-19</atitle><jtitle>JCI insight</jtitle><stitle>JCI INSIGHT</stitle><date>2021-02-22</date><risdate>2021</risdate><volume>6</volume><issue>4</issue><artnum>143299</artnum><eissn>2379-3708</eissn><abstract>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.</abstract><cop>ANN ARBOR</cop><pub>Amer Soc Clinical Investigation Inc</pub><pmid>33444289</pmid><doi>10.1172/jci.insight.143299</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-8380-3607</orcidid><oa>free_for_read</oa></addata></record> |
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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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