O1019: Monocyte biomarker offers early screening tool for identifying sepsis in children presenting to the Emergency Room

Background: Early determination of disease severity in an emergency setting is paramount for improving patient outcomes and healthcare costs. Monocyte anisocytosis, quantified as monocyte distribution width (MDW), has been shown to correspond with immune dysregulation in sepsis, severe COVID-19, and Multisystem Inflammatory Syndrome in Children in retrospective analyses. Here, we tested whether MDW, if collected at time of presentation to the emergency department, could accurately identify severe infection/sepsis in children.

Methods: We designed a prospective study to analyze MDW from leftover whole blood samples that were collected from children < 18 years of age upon presentation to the emergency room at either Mass General for Children or Johns Hopkins Children’s Center between 6/2022-6/2024. Samples were analyzed on a UniCel DxH 900 hematology analyzer (Beckman Coulter, Inc., Brea, CA). Medical information was extracted from electronic medical records; children were assessed for sepsis using Sepsis 2 criteria. Outcomes were analyzed by ANOVA, and receiver operating characteristic (ROC) curve assessed accuracy of MDW in identifying pediatric sepsis.

Results: Blood samples from 1,395 children were prospectively collected and analyzed. The mean age of participants was 8.2 years (standard deviation [SD] 5.4 years). The majority of children were White and non-Hispanic; an additional 28% identified as Black, 24% as Hispanic. The median MDW of children with sepsis who were subsequently identified with an infection was 25.4 (SD 3.8). Children with sepsis and suspected infection had an MDW of 24 (SD 6.3). These MDW values were significantly higher than values seen in children without infection, or children with mild infection (MDW, 19.6 and 19.3 respectively; p < 0.0001 and p = 0.0005 when compared with children with sepsis/confirmed infection). ROC analysis revealed an area under the curve of 77 suggesting MDW is an effective screening tool for sepsis in children. A dual threshold cutoff of 20 and 28 for low/high suspicion of sepsis is proposed.

Conclusion: MDW can readily be measured during the initial complete blood count (CBC) upon presentation to the emergency room, offering an early objective marker of sepsis in children. Rapidly identifying patients at high risk of sepsis may improve outcomes, while establishing a lower MDW threshold may inform which patients may be safely discharged. Further analyses testing MDW using alternative sepsis definitions are underway.