Sepsis Biomarkers: Our Experience and a Review in New Biomarkers

Background: Sepsis represents a dysregulated immune response to infection that leads to organ dysfunction. A wide range of biomarkers, measured by different technologies, are being investigated for sepsis diagnosis, prognosis, and differentiation from Systemic Inflammatory Response Syndrome (SIRS). Early diagnosis of sepsis with improved markers would allow prompt treatment, which is imperative in reducing mortality and morbidity. Methods: In our case-series study, we enrolled 174 patients who were admitted to and received treatment in the Intensive Care Unit (ICU) of our hospital (sepsis: n = 103, SIRS: n = 71). Specific parameters measured included procalcitonin (PCT), C-reactive protein (CRP), and cytokines (IL-6, IL-8, TNF-alpha). Results: We observed higher values of laboratory biomarkers in patients with sepsis compared to the SIRS group: PCT 10.2 ± 18.7 ng/ml vs 0.26 ± 0.18 ng/ml, CRP 148 ± 100 mg/L vs 42 ± 45 mg/L, IL-6 286 ± 330 pg/ml vs 21.01 ± 27.5 pg/ml, IL-8 310 ± 292 pg/ml vs 129 ± 32.69 pg/ml, TNF-alpha 131.15 ± 125.96 pg/ml vs 33.55 ± 118.87 pg/ml. A multiple comparison test demonstrated a highly statistically significant difference between groups for PCT, CRP, IL-6, IL-8, TNF-alpha. ROC curve analysis showed high sensitivity (97%) and specificity (93%) for PCT at a threshold of 0.5 ng/ml, and 100% specificity at 2 ng/ml. Other parameters demonstrated lower diagnostic accuracy. Conclusion: IL-6, IL-8, CRP, and TNF-alpha are sensitive tests for sepsis diagnosis but lack high specificity. PCT is the best marker, as it demonstrates both high sensitivity and specificity. New biomarkers of sepsis: presepsin, pro-adrenomedullin, microRNAs, transcriptomics, proteomics, and markers of neutrophil activation are currently under investigation, but further validation is needed.