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

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.

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.