A 29-mRNA Host Response Test from Blood Accurately Distinguishes Bacterial and Viral Infections Among Emergency Department Patients

Abstract

Study designWhether or not to administer antibiotics is a common and challenging clinical decision in patients with suspected infections presenting to the emergency department (ED). We prospectively validate InSep, a 29-mRNA blood-based host response test for the prediction of bacterial and viral infections.MethodsThe PROMPT trial is a prospective, non-interventional, multi-center randomized, controlled clinical trial that enrolled 397 adult patients presenting to the ED with signs of acute infection and at least one vital sign change. The infection status was adjudicated using chart review (including a syndromic molecular respiratory panel, procalcitonin and C-reactive protein) by three infectious disease physicians blinded to InSep results. InSep (version BVN-2) was performed using PAXgene Blood RNA processed and quantified on NanoString nCounter SPRINT. InSep results (likelihood of bacterial and viral infection) were compared to the adjudicated infection status.ResultsSubject mean age was 64 years, comorbidities were significant for diabetes (17.1%), chronic obstructive pulmonary disease (13.6%), and severe neurological disease (6.8%); 16.9% of subjects were immunocompromised. Infections were adjudicated as bacterial (14.1%), viral (11.3%) and noninfected (0.25%): 74.1% of subjects were adjudicated as indeterminate. InSep distinguished bacterial vs. viral/noninfected patients and viral vs. bacterial/noninfected patients using consensus adjudication with AUROCs of 0.94 (95% CI 0.90-0.99) and 0.90 (95% CI 0.83-0.96), respectively. AUROCs for bacterial vs. viral/noninfected patients were 0.88 (95%CI 0.79-0.96) for PCT, 0.80 (95% CI 0.72-89) for CRP and 0.78 (95% CI 0.69-0.87) for white blood cell counts (of note, the latter biomarkers were provided as part of clinical adjudication). To enable clinical actionability, InSep incorporates score cutoffs to allocate patients into interpretation bands. The Very Likely (rule in) InSep bacterial band showed a specificity of 98% compared to 94% for the corresponding PCT band (>0.5 ug/L); the Very Unlikely (rule-out) band showed a sensitivity of 95% for InSep compared to 86% for PCT. For the detection of viral infections, InSep demonstrated a specificity of 93% for the Very Likely band (rule in) and a sensitivity of 96% for the Very Unlikely band (rule out).ConclusionInSep demonstrated high accuracy for predicting the presence of both bacterial and viral infections in ED patients with suspected acute infections or suspected sepsis. When translated into a rapid, point-of-care test, InSep will provide ED physicians with actionable results supporting early informed treatment decisions to improve patient outcomes while upholding antimicrobial stewardship.Take-home messageInSep host response test is a point-of-care test providing with accuracy the likelihood for bacterial or viral infection for patients admitted at the emergencies InSep provided information on the likelihood of bacterial co-infection among patients with COVID-19.

A 29-Mrna Host Response Whole-Blood Signature Improves Prediction of 28-Day Mortality and 7-Day Intensive Care Unit Care in Adults Presenting to the Emergency Department With Suspected Acute Infection and/or Sepsis

“…Proprietary machine learning classifiers were used to process gene expression level data (24) and to generate three separate, prespecified scores for the likelihoods of (1) bacterial infection, (2) viral infection, and (3) severe outcome. The performance of the algorithms for determining the likelihood of bacterial and viral infection (IMX-BVN-2) has been previously described elsewhere (25) and in the same Greek ED patient cohort (26). The current study therefore focused on the performance of the severity risk score.…”

Heparin Binding Protein for the Early Diagnosis and Prognosis of Sepsis in the Emergency Department: The Prompt Multicenter Study

“…PROMPT is a confirmatory study in another healthcare setting testing, however, another platform of measurement of HBP than the previous studies and aiming to use HBP as a tool for screening of the risk of early death and not of general unfavorable outcome. (10).…”

Detection of Viral Infection and Bacterial Coinfection and Superinfection in Coronavirus Disease 2019 Patients Presenting to the Emergency Department Using the 29-mRNA Host Response Classifier IMX-BVN-3: A Multicenter Study

“…Inflammatix Bacterial Viral Noninfected version 3 (IMX-BVN-3) is a host messenger RNA (mRNA)-based classifier to determine the likelihood of a bacterial infection and the likelihood of a viral infection [7,8]. Several clinical studies have demonstrated its high accuracy for the detection of bacterial and/or viral infections [9][10][11][12].…”