TY - JOUR
T1 - Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19
AU - Scozzi, Davide
AU - Cano, Marlene
AU - Ma, Lina
AU - Zhou, Dequan
AU - Zhu, Ji Hong
AU - O'Halloran, Jane A.
AU - Goss, Charles
AU - Rauseo, Adriana M.
AU - Liu, Zhiyi
AU - Sahu, Sanjaya K.
AU - Peritore, Valentina
AU - Rocco, Monica
AU - Ricci, Alberto
AU - Amodeo, Rachele
AU - Aimati, Laura
AU - Ibrahim, Mohsen
AU - Hachem, Ramsey
AU - Kreisel, Daniel
AU - Mudd, Philip A.
AU - Kulkarni, Hrishikesh S.
AU - Gelman, Andrew E.
N1 - Funding Information:
Washington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345. AEG is supported by Washington University ICTS COVID-19 Research Program, The Foundation for Barnes-Jewish Hospital, NIH R01HL094601, and NIH P01AI116501. HSK is supported by NIH K08HL148510 and the Children's Discovery Institute. JAO, CG, and PAM are supported by Washington University ICTS grant UL1TR002345 from the National Center for Advancing Translational Sciences of the NIH. Sample procurement and patient outcome data collection were supported by a $250,000 grant from The Foundation for Barnes-Jewish Hospital and Washington University ICTS NIH grants UL1TR002345 and P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.
Publisher Copyright:
© 2021, Scozzi et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2021/2/22
Y1 - 2021/2/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101450266&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.143299
DO - 10.1172/jci.insight.143299
M3 - Article
C2 - 33444289
AN - SCOPUS:85101450266
SN - 2379-3708
VL - 6
JO - JCI insight
JF - JCI insight
IS - 4
M1 - e143299
ER -