Blood biomarker and Raman analysis of leukocytes in the multicenter INTELLIGENCE trials: at the Intensive Care Unit (INTELLIGENCE-1) and the Emergency Department (INTELLIGENCE-2)

BACKGROUND: Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, goes along with a complex and not yet fully understood host response. Despite many different biomarkers, optimal screening tools to identify patients with sepsis are still needed. In a previous, single-center clinical trial with well-defined and well-separated patient cohorts, a new biophotonic marker based on the Raman spectroscopic characterization of leukocytes showed added value to stratify patients and identify infection and sepsis.

RESULTS: In the INTELLIGENCE studies, 279 patients from six centres in two countries were analysed and the Raman spectra of ~1500 leukocytes per patient measured within only 1 hour. This marks a huge step from bench to bedside regarding usability and technology readiness level of Raman spectroscopy in multicentre clinical trials. With a discriminatory power comparable to individual conventional biomarkers (CRP, PCT, IL-6, suPAR), the Raman score of leukocytes could not provide added value to the clinical discrimination of sepsis in the INTELLIGENCE-1 study cohorts of intensive care patients with infections. When translating the classification model from INTELLIGENCE-1 to the heterogeneous patient cohort recruited at the emergency department of the double-blinded INTELLIGENCE-2 trial, the Raman score failed to provide added value.

CONCLUSIONS: In theory, Raman assessment of leukocytes might still be a promising tool for sepsis diagnosis and patient stratification, but there is more basic, translational and clinical research needed to refine its usability and clinical role, probably also taking questions of the pathophysiology of the dysregulated host response for a phenotype stratification into account.