From sepsis biomarker discovery to regulated in vitro diagnostics: evidence, certification status and implementation gaps
TL;DR
The Mini Review examines selected sepsis biomarkers and diagnostic platforms with emphasis on technologies that have reached certified or cleared IVD implementation, or that illustrate a credible route toward regulated use, set against an evolving regulatory landscape shaped by the EU IVDR and the phased rollout of EUDAMED.
Abstract
Sepsis remains a diagnostic challenge because early clinical manifestations are non-specific and microbiological confirmation often arrives too late to guide first-hour decisions. The 2026 Surviving Sepsis Campaign guidelines reinforce early clinical recognition using validated clinical scores, appropriate diagnostic strategies, and responsible antimicrobial use and de-escalation. Yet, initial management still frequently occurs under diagnostic uncertainty. Hundreds of biomarkers have been proposed to improve sepsis diagnosis, risk stratification and treatment guidance; however, only a limited subset has progressed from discovery to regulated in vitro diagnostic use. This Mini Review examines selected sepsis biomarkers and diagnostic platforms with emphasis on technologies that have reached certified or cleared IVD implementation, or that illustrate a credible route toward regulated use. We discuss conventional soluble biomarkers such as procalcitonin, C-reactive protein, interleukin-6 and lactate; emerging severity and host-response markers including presepsin, pancreatic stone protein, monocyte distribution width and mid-regional proadrenomedullin; transcriptomic and cellular host-response tests; and functional immune technologies such as the LPS-induced TNF-alpha release assay, also referred to as TARA. Rather than ranking biomarkers solely by diagnostic performance, we emphasize intended clinical use, biological rationale, sample type, turnaround time, regulatory status and workflow compatibility. The review highlights the persistent gap between biomarker discovery and clinical deployment, set against an evolving regulatory landscape shaped by the EU IVDR and the phased rollout of EUDAMED. Future sepsis diagnostics will likely move beyond isolated inflammatory analytes toward integrated host-response, near-patient and functional immune assays able to support early triage, risk stratification, antimicrobial stewardship and precision immune monitoring.