Validation of a host response test to distinguish bacterial and viral respiratory infection

EBioMedicine. 2019 Oct;48:453-461. doi: 10.1016/j.ebiom.2019.09.040. Epub 2019 Oct 17.

Abstract

Background: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases.

Methods: Subjects with acute respiratory illness were enrolled in participating emergency departments. Reference standard was an adjudicated diagnosis of bacterial infection, viral infection, both, or neither. An 87-transcript signature for distinguishing bacterial, viral, and noninfectious illness was measured from peripheral blood using RT-PCR. Performance characteristics were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness. Subjects with bacterial-viral coinfection and microbiologically-negative suspected bacterial infection were also evaluated. Performance was compared to procalcitonin.

Findings: 151 subjects with microbiologically confirmed, single-etiology illness were tested, yielding AUROCs 0•85-0•89 for bacterial, viral, and noninfectious illness. Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness, the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified 95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects with bacterial infection superimposed on chronic viral infection, the RT-PCR test identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected bacterial infection; the RT-PCR test identified bacterial infection more frequently than procalcitonin (82% vs 64%, p = 0•02).

Interpretation: The RT-PCR test offered similar diagnostic performance to procalcitonin in some subgroups but offered better discrimination in others such as viral vs. non-infectious illness and bacterial/viral coinfection. Gene expression-based tests could impact decision-making for acute respiratory illness as well as a growing number of other infectious and non-infectious diseases.

Keywords: Biomarkers; Coinfection; Diagnosis; Gene expression; Precision medicine; Respiratory tract infections.

MeSH terms

  • Adult
  • Aged
  • Bacterial Infections / diagnosis*
  • Bacterial Infections / microbiology
  • Biomarkers*
  • Coinfection / diagnosis
  • Diagnosis, Differential
  • Female
  • Host-Pathogen Interactions*
  • Humans
  • Male
  • Middle Aged
  • Precision Medicine
  • Real-Time Polymerase Chain Reaction / methods
  • Real-Time Polymerase Chain Reaction / standards
  • Reproducibility of Results
  • Respiratory Tract Infections / diagnosis*
  • Respiratory Tract Infections / etiology*
  • Virus Diseases / diagnosis*
  • Virus Diseases / virology
  • Workflow
  • Young Adult

Substances

  • Biomarkers