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Background <p>Sepsis and septic shock are life-threatening conditions with high mortality, presenting challenges in predicting disease severity and outcomes. Cell-free mitochondrial DNA (mtDNA) has emerged as a potential mediator in sepsis pathogenesis, acting as a damage-associated molecular pattern (DAMP) that exacerbates inflammation. The present study aimed to assess cell-free mtDNA levels as predictors of mortality and disease severity, and to determine their correlation with established clinical markers.</p> Methods <p>A prospective study enrolled 150 participants, including healthy controls (<i>n</i> = 50) and patients (<i>n</i> = 100, of which 50 had sepsis and 50 had septic shock). Plasma cell-free mtDNA levels were quantified using RT-qPCR, and Receiver operating characteristic (ROC) curves were used to evaluate the predictive ability of cell-free mtDNA for 28-day mortality. The cell-free mtDNA correlated with clinical markers, including C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE II), Procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), and lactate.</p> Results <p>Cell-free mtDNA levels were significantly elevated in sepsis and septic shock patients compared to controls, and higher in septic shock compared to sepsis patients. Non-survivors exhibited significantly higher cell-free mtDNA levels than survivors across both sepsis and septic shock subgroups. Cell-free mtDNA demonstrated a superior predictive value for 28-day mortality, area under the curve (AUC = 0.865) compared to clinical markers (CRP, SOFA, PCT, NLR, and Lactate). Furthermore, cell-free mtDNA levels showed a positive correlation with CRP, followed by SOFA, NLR, and PCT.</p> Conclusion <p>Elevated circulating cell-free mtDNA levels were associated with severity and mortality in sepsis and septic shock, and may act as a valuable molecular tool for predicting disease outcomes. The study’s findings warrant further investigation into the potential of cell-free mtDNA as a future component of clinical management strategies in sepsis.</p>

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Assessment of circulating cell-free mitochondrial DNA as a damage associated molecular pattern in predicting severity and mortality of sepsis and septic shock patients

  • 期刊论文

  • 发表日期：

    2026年1月13日

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  • Bushra,
  • Safia Begum,
  • Shaik Iqbal Ahmed,
  • Akbar Pasha,
  • Ramesh Kande,
  • Mohammed Affan Osman Khan,
  • Aleem Ahmed Khan

摘要

Background

Sepsis and septic shock are life-threatening conditions with high mortality, presenting challenges in predicting disease severity and outcomes. Cell-free mitochondrial DNA (mtDNA) has emerged as a potential mediator in sepsis pathogenesis, acting as a damage-associated molecular pattern (DAMP) that exacerbates inflammation. The present study aimed to assess cell-free mtDNA levels as predictors of mortality and disease severity, and to determine their correlation with established clinical markers.

Methods

A prospective study enrolled 150 participants, including healthy controls (n = 50) and patients (n = 100, of which 50 had sepsis and 50 had septic shock). Plasma cell-free mtDNA levels were quantified using RT-qPCR, and Receiver operating characteristic (ROC) curves were used to evaluate the predictive ability of cell-free mtDNA for 28-day mortality. The cell-free mtDNA correlated with clinical markers, including C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE II), Procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), and lactate.

Results

Cell-free mtDNA levels were significantly elevated in sepsis and septic shock patients compared to controls, and higher in septic shock compared to sepsis patients. Non-survivors exhibited significantly higher cell-free mtDNA levels than survivors across both sepsis and septic shock subgroups. Cell-free mtDNA demonstrated a superior predictive value for 28-day mortality, area under the curve (AUC = 0.865) compared to clinical markers (CRP, SOFA, PCT, NLR, and Lactate). Furthermore, cell-free mtDNA levels showed a positive correlation with CRP, followed by SOFA, NLR, and PCT.

Conclusion

Elevated circulating cell-free mtDNA levels were associated with severity and mortality in sepsis and septic shock, and may act as a valuable molecular tool for predicting disease outcomes. The study’s findings warrant further investigation into the potential of cell-free mtDNA as a future component of clinical management strategies in sepsis.