Cell-Free Nuclear and Mitochondrial DNA as Potential Biomarkers for Assessing Sepsis Severity

Sepsis continues to be a significant public health challenge despite advances in understanding its pathophysiology and management strategies. Therefore, this study evaluated the value of cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) for assessing the severity and prognosis of sepsis. Ninety-four patients were divided into three groups: infection (n = 32), sepsis (n = 30), and septic shock (n = 32). Plasma samples were collected at the time of diagnosis, and cfDNA concentrations were determined by qPCR assay. The results showed that plasma cfDNA levels increased with the severity of the disease. To distinguish between patients with infection and those with sepsis, the biomarker L1PA2₉₀ achieved the highest AUC of 0.817 (95% CI: 0.725-0.909), demonstrating a sensitivity of 77.0% and a specificity of 79.3%. When cf-nDNA was combined with the SOFA score, there was a significant improvement in the AUC (0.916 (0.853-0.979)), sensitivity (88.1%), and specificity (80.0%). Moreover, patients admitted to the ICU after being diagnosed with sepsis had significantly higher cf-nDNA concentrations. In patients admitted to the ICU, combining cf-nDNA with the SOFA score yielded an AUC of 0.753 (0.622-0.857), with a sensitivity of 95.2% and a specificity of 50.0%. cfDNA can differentiate between patients with infection and those with sepsis. It can also identify patients who are likely to be admitted to the ICU by predicting those with indications for intensive care, suggesting its potential as a biomarker for sepsis.