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[Preprint]. 2020 Jul 30:2020.07.30.227553. [Version 1] doi: 10.1101/2020.07.30.227553

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, 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
PMCID: PMC7402031  PMID: 32766574

SUMMARY

Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether the appearance of cell-free MT-DNA is linked to poor COVID-19 outcomes remains undetermined. Here, we quantified circulating MT-DNA in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at the time of hospital presentation. Circulating MT-DNA were sharply elevated in patients who eventually died, required ICU admission or intubation. Multivariate regression analysis revealed that high circulating MT-DNA levels is an independent risk factor for all of these outcomes after adjusting for age, sex and comorbidities. Additionally, we found that circulating MT-DNA has a similar or superior area-under-the curve when compared to clinically established measures of systemic inflammation, as well as emerging markers currently of interest as investigational targets for COVID-19 therapy. These results show that high circulating MT-DNA levels is a potential indicator for poor COVID-19 outcomes.

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