Biomarkers of sepsis: time for a reappraisal

Charalampos Pierrakos, Dimitrios Velissaris, Max Bisdorff, John C Marshall, Jean-Louis Vincent, Charalampos Pierrakos, Dimitrios Velissaris, Max Bisdorff, John C Marshall, Jean-Louis Vincent

Abstract

Introduction: Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers.

Methods: Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms "Biomarker" AND "Sepsis." There were no restrictions by age or language, and all studies, clinical and experimental, were included.

Results: We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis.

Conclusions: The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.

Keywords: C-reactive protein; Diagnosis; Infection; Procalcitonin; Prognosis; Validation.

Conflict of interest statement

JLV is the Editor-in-Chief of Critical Care and has no other conflicts of interest.

The other authors declare that they have no relevant financial interests.

Figures

Fig. 1
Fig. 1
Changes over time in the a number of references meeting our search criteria and b number of new biomarkers referred to in identified references

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