Translational Biomarkers in Sepsis Management

Abstract

Sepsis remains one of the most lethal conditions encountered in modern intensive care, killing roughly one in five affected patients despite decades of research and billions spent on drug development. A major part of the problem is that clinicians still lack reliable tools to catch sepsis early, track how it is progressing in real time, and figure out which patients will respond to which treatments. Traditional biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) have been around for years, but they are blunt instruments -- elevated in all sorts of inflammatory conditions, not just sepsis, and often too slow to reflect rapid clinical deterioration. There is a real need for better biomarkers that can do more than just confirm what the clinician already suspects. In this study, we evaluated five categories of translational biomarkers - acute-phase proteins, cytokine panels, cell-surface markers, metabolomic signatures, and host-response transcriptomic scores -- across four clinically relevant tasks: early sepsis detection within 6 hours of onset, severity stratification at ICU admission, treatment response monitoring over 72 hours, and 28-day mortality prediction. We analysed data from 1,486 ICU patients across five European academic medical centres (Berlin, Rome, Madrid, Vienna, and Zurich) admitted between March 2018 and November 2021. We developed a Sepsis Biomarker Utility Score (SBUS) that integrates diagnostic accuracy, prognostic power, treatment-response sensitivity, turnaround time, and cost feasibility. Host-response transcriptomic scores achieved the highest overall SBUS (0.918), driven by superior early detection (AUROC 0.94) and mortality prediction (AUROC 0.91). Cytokine panels excelled specifically at treatment-response monitoring (sensitivity 0.89 at 24 hours). These findings suggest that combining rapid transcriptomic profiling with serial cytokine measurement could substantially improve sepsis management in the ICU.