Circulating Mitochondrial DNA is an Early Indicator of Severe Illness and Mortality from COVID-19

Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating MT-DNA levels could be used to predict the development of poor COVID-19 outcomes remains undetermined. Here, we measured circulating MT-DNA levels 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 demonstrated MT-DNA levels as an independent risk factor for all of these outcomes after adjusting for age, sex and comorbidities. Importantly, we found MT-DNA levels had a similar or superior area-under-the curve when compared to clinically established inflammatory indicators, as well as emerging markers currently of interest as targets for investigational therapies. These results show that high circulating MT-DNA levels are a potential indicator of poor COVID-19 outcomes.