A comparison of host response strategies to distinguish bacterial and viral infection

PLoS One. 2021 Dec 14;16(12):e0261385. doi: 10.1371/journal.pone.0261385. eCollection 2021.

Abstract

Objectives: Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI).

Methods: In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene expression mRNA panel were measured in 286 subjects with ARI from four emergency departments. Multinomial logistic regression and leave-one-out cross validation were used to evaluate the protein and mRNA tests.

Results: The mRNA panel performed better than alternative strategies to identify bacterial infection: AUC 0.93 vs. 0.83 for the protein panel and 0.84 for procalcitonin (P<0.02 for each comparison). This corresponded to a sensitivity and specificity of 92% and 83% for the mRNA panel, 81% and 73% for the protein panel, and 68% and 87% for procalcitonin, respectively. A model utilizing all three strategies was the same as mRNA alone. For the diagnosis of viral infection, the AUC was 0.93 for mRNA and 0.84 for the protein panel (p<0.05). This corresponded to a sensitivity and specificity of 89% and 82% for the mRNA panel, and 85% and 62% for the protein panel, respectively.

Conclusions: A gene expression signature was the most accurate host response strategy for classifying subjects with bacterial, viral, or non-infectious ARI.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bacteria / isolation & purification*
  • Bacterial Infections / complications
  • Bacterial Infections / diagnosis*
  • Bacterial Infections / metabolism
  • Bacterial Infections / microbiology
  • Biomarkers / metabolism
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / metabolism
  • Diagnosis, Differential
  • Emergency Service, Hospital
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Procalcitonin / genetics
  • Procalcitonin / metabolism
  • Prognosis
  • ROC Curve
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Respiratory Tract Infections / epidemiology*
  • Respiratory Tract Infections / etiology
  • Respiratory Tract Infections / metabolism
  • Respiratory Tract Infections / pathology
  • Retrospective Studies
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • United States / epidemiology
  • Virus Diseases / complications
  • Virus Diseases / diagnosis*
  • Virus Diseases / virology
  • Viruses / isolation & purification*

Substances

  • Biomarkers
  • CRP protein, human
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Procalcitonin
  • Receptors, Immunologic
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • C-Reactive Protein