JCI Insight (Feb 2021)

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

  • 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

Journal volume & issue
Vol. 6, no. 4

Abstract

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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.

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