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Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19
Davide Scozzi, … , Hrishikesh S. Kulkarni, Andrew E. Gelman
Davide Scozzi, … , Hrishikesh S. Kulkarni, Andrew E. Gelman
Published January 14, 2021
Citation Information: JCI Insight. 2021;6(4):e143299. https://doi.org/10.1172/jci.insight.143299.
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Clinical Medicine COVID-19 Immunology

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

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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.Funding Washington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345.

Authors

Davide Scozzi, Marlene Cano, Lina Ma, Dequan Zhou, Ji Hong Zhu, Jane A. O’Halloran, Charles Goss, Adriana M. Rauseo, Zhiyi Liu, Sanjaya K. Sahu, Valentina Peritore, Monica Rocco, Alberto Ricci, Rachele Amodeo, Laura Aimati, Mohsen Ibrahim, Ramsey Hachem, Daniel Kreisel, Philip A. Mudd, Hrishikesh S. Kulkarni, Andrew E. Gelman

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Figure 3

High circulating MT-DNA levels predict a higher risk of ICU requirement and intubation in COVID-19 patients.

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High circulating MT-DNA levels predict a higher risk of ICU requirement ...
Plasma for determination of circulating levels of MT-CYTB was obtained at time of hospital presentation. Box-and-whisker plots of MT-CYB levels in relation to (A) ICU admission and (C) intubation in COVID-19 patients. The box plots depict the minimum and maximum values (whiskers), the upper and lower quartiles, and the median. The length of the box represents the interquartile range. Empty dots indicate alive patients and shaded dots indicate deceased patients. ROC curves in predicting the outcome (B) ICU and (D) intubation based on MT-CYTB levels. Statistical significance was determined using Mann-Whitney U test (****P <.0001).

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