Abstract
Sepsis remains a primary cause of mortality in intensive care units (ICUs) globally, demanding rapid, reliable biomarkers to evaluate disease severity and prognosticate clinical outcomes. Cell-free mitochondrial DNA (cf-mtDNA), acting as a potent damage-associated molecular pattern (DAMP), has emerged as a promising surrogate for cellular injury and systemic inflammation. This prospective observational cohort study evaluated the prognostic accuracy of plasma cf-mtDNA quantification for predicting 28-day all-cause mortality and organ dysfunction in 184 critically ill adult sepsis patients admitted to a tertiary medical ICU. Plasma cf-mtDNA copy numbers targeting the human NADH dehydrogenase subunit 1 (ND1) gene were measured via quantitative real-time polymerase chain reaction (qPCR) within 12 hours of ICU admission. Median baseline cf-mtDNA levels were significantly elevated in non-survivors compared to survivors (4,820 copies/µL vs. 1,150 copies/µL; p < 0.001) and correlated robustly with Sequential Organ Failure Assessment (SOFA) scores (r = 0.62, p < 0.001) and serum lactate (r = 0.54, p < 0.001). Receiver operating characteristic (ROC) analysis demonstrated an area under the curve (AUC) of 0.86 (95% CI: 0.80–0.92) for cf-mtDNA predicting 28-day mortality, superior to procalcitonin (AUC 0.71) and serum lactate (AUC 0.77). Multivariable Cox proportional hazards regression identified log10 cf-mtDNA as an independent predictor of 28-day mortality (adjusted HR 2.38, 95% CI: 1.54–3.68, p < 0.001). Early quantification of plasma cf-mtDNA provides robust prognostic value for stratifying mortality risk and organ failure in adult sepsis patients, supporting its potential utility in precision critical care triage.
