Titel: A host gene signature for diagnosis and risk stratification of acute infection and sepsis at hospital admission: HostDxTM Sepsis
Art: Abstractautor
Session: Workshop 05
Diagnostic Stewardship - "Meet the needs of your partners!" (FG DKM, FG QD)

Referent: Oliver Liesenfeld (Burlingame/US)

Abstract - Text


Acute infections and sepsis are leading causes of morbidity and mortality worldwide. In Germany and other countries, the number of patients visiting emergency departments has increased substantially in recent years. Diagnostic procedures to evaluate patients with acute infections and suspected sepsis are inaccurate or slow. Analysis of host-response signatures using RNA expression has been described for diagnosis and risk stratification. We here describe the development of HostDx™ Sepsis, a 30-host-gene PCR test that identifies i) the presence of an infection, ii) the type of infection (viral or bacterial), and iii) the severity of the infection using whole blood. The HostDx Sepsis test is being developed as a cartridge-based, sample-to-answer, quantitative assay with turn-around time of less than 30 minutes.   


To identify gene signatures specific for presence, type and severity of infection, we analyzed publicly available microarray and NGS gene expression data sets from cohorts of children and adults with community- and hospital-acquired infection and sepsis. Gene sets to distinguish between infections and non-infectious inflammation, between viral and bacterial infections, and that can predict the severity of infection were discovered and validated in 38 independent cohorts (total N=2452) to establish clinical performance.


Validation performance for the presence of any bacterial infection in a hospital population showed a 94% sensitivity and 60% specificity (99% negative predictive value at 15% prevalence). The mean area under the receiver operator characteristics curve (AUROC) was 0.88 for prediction of 30-day mortality, markedly improving AUROCs for laboratory parameters and/or clinical scores including lactate and SOFA. To demonstrate proof of feasibility, gene signatures distinguishing between viral and bacterial infections were successfully converted to rapid multiplex PCR assay formats, with correlation of 0.95 to a NanoString® reference standard (digital detection and quantification of unique transcripts).

Discussion & Conclusions

Emergency physicians currently rely on a battery of tests with low accuracy to diagnose acute infections and sepsis. The host-response signatures described demonstrated high diagnostic and prognostic accuracy in numerous independent cohorts. As a rapid triage assay HostDx Sepsis will allow for improved decision making for antibiotics, downstream testing, and level-of-care decisions.