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

Area of Science:

• Biomarkers
• Molecular Diagnostics
• Critical Care Medicine

Background:

• Sepsis remains a major global health concern, necessitating improved diagnostic and prognostic tools.
• Despite advancements, accurately assessing sepsis severity and predicting patient outcomes remains challenging.
• Cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) are emerging as potential indicators in various diseases.

Purpose of the Study:

• To evaluate the diagnostic and prognostic value of cf-nDNA and cf-mtDNA in sepsis patients.
• To assess the correlation between cfDNA levels and sepsis severity.
• To determine if cfDNA can predict the need for intensive care unit (ICU) admission.

Main Methods:

• Plasma cfDNA concentrations were measured using qPCR in 94 patients categorized into infection, sepsis, and septic shock groups.
• Analysis included receiver operating characteristic (ROC) curves to assess diagnostic accuracy.
• Combined analysis of cf-nDNA with the Sequential Organ Failure Assessment (SOFA) score was performed.

Main Results:

• Plasma cfDNA levels significantly increased with sepsis severity.
• The biomarker L1PA2₉₀ showed good performance in distinguishing infection from sepsis (AUC=0.817).
• Combining cf-nDNA with the SOFA score improved AUC, sensitivity, and specificity for predicting sepsis severity and ICU admission.

Conclusions:

• Plasma cfDNA, particularly cf-nDNA, serves as a valuable biomarker for assessing sepsis severity.
• cfDNA can differentiate between infection and sepsis and predict ICU admission, indicating its potential in sepsis management.
• The combination of cf-nDNA and SOFA score enhances prognostic accuracy in sepsis patients.