| Autor: |
Scozzi D; Division of Cardiothoracic Surgery, Department of Surgery., Cano M; Division of Pulmonary and Critical Care Medicine, Department of Medicine., Ma L; Division of Pulmonary and Critical Care Medicine, Department of Medicine., Zhou D; Division of Cardiothoracic Surgery, Department of Surgery., Zhu JH; Division of Cardiothoracic Surgery, Department of Surgery., O'Halloran JA; Division of Infectious Diseases, Department of Medicine; and., Goss C; Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA., Rauseo AM; Division of Infectious Diseases, Department of Medicine; and., Liu Z; Division of Cardiothoracic Surgery, Department of Surgery., Sahu SK; Division of Pulmonary and Critical Care Medicine, Department of Medicine., Peritore V; Division of Thoracic Surgery and., Rocco M; Division of Anesthesiology, Department of Medical-Surgical Science and Translational Medicine, Sapienza University of Rome, Rome, Italy., Ricci A; Division of Pulmonology, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy., Amodeo R; Laboratory Analysis-Flow Cytometry Section, Sapienza University of Rome, Rome, Italy., Aimati L; Laboratory Analysis-Flow Cytometry Section, Sapienza University of Rome, Rome, Italy., Ibrahim M; Division of Cardiothoracic Surgery, Department of Surgery.; Division of Thoracic Surgery and., Hachem R; Division of Pulmonary and Critical Care Medicine, Department of Medicine., Kreisel D; Division of Cardiothoracic Surgery, Department of Surgery., Mudd PA; Division of Emergency Medicine., Kulkarni HS; Division of Pulmonary and Critical Care Medicine, Department of Medicine.; Department of Molecular Microbiology, and., Gelman AE; Division of Cardiothoracic Surgery, Department of Surgery.; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. |
| Abstrakt: |
BackgroundMitochondrial 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.MethodsWe 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.ResultsCirculating 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.ConclusionThese results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.FundingWashington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345. |
