Learning Objectives: Biomarker facilitated sepsis diagnosis is needed given specificity limitations of clinical diagnostics. Sepsis-mediated host immune gene expression may represent a novel diagnostic approach. An RT-qPCRbased test, SeptiCyte® Lab, that quantifies expression levels of 4 genes involved in the septic host response, has been validated for septic adults. Herein we report the first investigation of SeptiCyte® Lab in a pediatric critical care setting. Methods: We conducted an IRB-approved, prospective, observational study enrolling 12 children undergoing CPB surgery to repair congenital heart disease (CHD; infection negative) and 28 children with clinical severe sepsis (CSS; 16 culture+, 12 culture-). Septic children had confirmed/suspected infection (microbial culture orders, antimicrobial prescription), exhibited SIRS criteria, and demonstrated cardiovascular ± pulmonary organ dysfunction. Immune competent and incompetent patients were included in the sepsis cohort. Demographic and admission illness severity data were collected. Next-generation sequencing (Illumina Mi-Seq) and RT-qPCR were used to analyze the transcriptome from peripheral blood collected at PICU admission. Results: CHD◊CSS descriptive data included age: 8.0 ± 6.2◊9.6 ± 6.4; gender: 42◊50% male; PRISM III: 6.2 ± 5.0◊7.8 ± 5.7; PELOD: 5.0 ± 2.9◊4.5 ± 2.6. SeptiCyte® Lab gene expression biomarkers strongly differentiated CHD and CSS patients (AUC 0.955; 95% CI: 0.88-1.00). SeptiCyte® Lab performance was similar when the samples were reanalyzed using RT-qPCR. There was no correlation (R2=0.01) between the SeptiCyte® Lab score and PRISM score, indicating that information provided by SeptiCyte® Lab is independent of illness severity, but instead reflects of the probability of sepsis. Conclusions: Our pilot investigation of SeptiCyte® Lab in a pediatric critical care setting demonstrates that this adult-derived gene signature may also facilitate diagnosis of sepsis in critically ill children. A broader investigation of the performance of the test among children with more heterogeneous care settings and infection diagnoses is warranted.

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