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 - 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 -