Cellular host response sepsis test for risk stratification of patients in the emergency department: A pooled analysis

Abstract Objectives Sepsis is one of the most common, costly, and misdiagnosed conditions in U.S. emergency departments (EDs). ED providers often treat on nonspecific signs, subjective suspicion, or presumption of infection, resulting in over‐ and undertreatment. An increased understanding of host response has opened a new direction for sepsis diagnostics. The IntelliSep test is a U.S. Food and Drug Administration–cleared cellular host response diagnostic that could help distinguish sepsis in ED settings. Our objective was to evaluate the potential of the cellular host response test to expedite appropriate care for patients who present with signs of infection. Methods We performed a pooled analysis of five adult (≥18 years) cohorts enrolled at seven geographically diverse U.S. sites in separate studies. Structured blinded adjudication was used to classify presence or absence of sepsis, and only patients with high confidence in the adjudicated label were included ( n = 1002), defined as patients for whom there was consensus in the determination of sepsis per the Sepsis‐3 and severe sepsis per the Sepsis‐2 definitions between both the independent adjudication panel and the site‐level physician. Results Among patients with signs or suspicion of infection, the test achieved similar or better performance compared to other indicators in identifying patients at high risk for sepsis (specificity > 83%) and significantly superior performance in identifying those at low risk (sensitivity > 92%; 0% sepsis‐associated mortality). The test also stratified severity of illness, as shown by 30‐day in‐hospital mortality ( p < 0.001), hospital length of stay ( p < 0.01), and use of hospital resources ( p < 0.001). Conclusions Our data suggest that the cellular host response test provides clinically actionable results for patients at both high and low risk for sepsis and provides a rapid, objective means for risk stratification of patients with signs of infection. If integrated into standard of care, the test may help improve outcomes and reduce unnecessary antibiotic use.