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; 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

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.