Authors: Davide Scozzi,¹Marlene Cano,²Lina Ma,²Dequan Zhou,¹Ji Hong Zhu,¹Jane A. O’Halloran,³Charles Goss,⁴Adriana M. Rauseo,³Zhiyi Liu,¹Sanjaya K. Sahu,²Valentina Peritore,⁵Monica Rocco,⁶Alberto Ricci,⁷Rachele Amodeo,⁸Laura Aimati,⁸Mohsen Ibrahim,^1,5Ramsey Hachem,²Daniel Kreisel,¹Philip A. Mudd,⁹Hrishikesh S. Kulkarni,^2,10 and Andrew E. Gelman^1,11

Abstract

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.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934921/