How nEMR3 Spotlights Early Sepsis and Tracking Survival

link.springer.com July 1, 2026

This single-center ICU study conducted at Sir Run Run Shaw Hospital evaluated neutrophil EMR3 (nEMR3), a biomarker calculated by normalizing a patient’s neutrophil EMR3 median fluorescence intensity to healthy controls, as a novel tool for both early sepsis diagnosis and dynamic risk stratification. The researchers utilized two independent, non-overlapping patient cohorts to test the biomarker.

The first cohort focused on early identification by comparing patients diagnosed with sepsis within 24 hours of ICU admission to non-septic critical controls and healthy individuals, while the second longitudinal cohort tracked serial nEMR3 trajectories from Day 0 to Day 7 in septic patients to evaluate its association with 28-day mortality.

Sepsis-3 adjudication was verified by blinded intensivists, and all biomarkers were measured via flow cytometry within 12 hours of blood collection.

The results demonstrated that nEMR3 holds strong potential as both a diagnostic and prognostic biomarker. In the early-identification cohort, nEMR3 was markedly lower in sepsis patients than in non-septic or healthy controls, outperforming traditional biomarkers like PCT, CRP, and nCD64 with an impressive area under the curve (AUC) of 0.944.

Longitudinally, while admission levels did not clearly differentiate outcomes, a distinct divergence emerged from Day 3 onward: non-survivors showed a persistent suppression or failure of nEMR3 recovery, whereas survivors demonstrated steady normalization.

The change in nEMR3 from Day 0 to Day 7 proved to be a highly informative predictor of 28-day mortality (AUC 0.882), notably outperforming time-matched SOFA scores.

Despite these promising findings, the authors highlighted several important caveats, including the study’s single-center design and the inherent risk of survivor bias and informative missingness in later longitudinal time points.

Additionally, the clinical implementation of nEMR3 will require rigorous assay harmonization, cross-platform reproducibility testing, and direct comparison with other immune-dysfunction markers. Nonetheless, the study concludes that nEMR3 offers a distinct, complementary perspective on the sepsis host response—acting as an early indicator of infection and a dynamic mirror of recovery or decline—that warrants further investigation in larger, multicenter cohorts.