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

Scozzi, D.; Cano, M.; MA, L.; Zhou, D.; Zhu, J. H.; O'Halloran, J. A.; Goss, C.; Rauseo, A.; Liu, Z.; Peritore, V.; Rocco, M.; Ricci, A.; Amodeo, R.; Aimati, L.; Ibrahim, M.; Hachem, R.; Kreisel, D.; Mudd, P. A.; Kulkarni, H. S.; Gelman, A. E.

doi:10.1101/2020.07.30.227553

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bioRxiv · 10.1101/2020.07.30.227553

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

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Abstract

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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Scozzi, D., Cano, M., MA, L., Zhou, D., Zhu, J. H., O'Halloran, J. A., Goss, C., Rauseo, A., Liu, Z., Peritore, V., Rocco, M., Ricci, A., Amodeo, R., Aimati, L., Ibrahim, M., Hachem, R., Kreisel, D., Mudd, P. A., Kulkarni, H. S., Gelman, A. E.. 2020-07-30. Circulating Mitochondrial DNA is an Early Indicator of Severe Illness and Mortality from COVID-19. https://doi.org/10.1101/2020.07.30.227553

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