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

• Published in: PloS one Vol. 16; no. 12; p. e0261385
• Main Authors: Ross, Melissa, Henao, Ricardo, Burke, Thomas W, Ko, Emily R, McClain, Micah T, Ginsburg, Geoffrey S, Woods, Christopher W, Tsalik, Ephraim L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.12.2021; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Antibiotics; Bacteria; Bacteria - isolation & purification; Bacterial diseases; Bacterial infections; Bacterial Infections - complications; Bacterial Infections - diagnosis; Bacterial Infections - metabolism; Bacterial Infections - microbiology; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; C-Reactive Protein - genetics; C-Reactive Protein - metabolism; Case-Control Studies; Chemokine CXCL10 - genetics; Chemokine CXCL10 - metabolism; Diagnosis, Differential; Emergency medical care; Emergency Service, Hospital; Enrollments; Etiology; Female; Follow-Up Studies; Gene expression; Genomics; Hospitals; Host-bacteria relationships; Humans; Illnesses; Immunoassay; Infection; Infections; IP-10 protein; Laboratories; Male; Medical diagnosis; Medicine and Health Sciences; Middle Aged; Pathogens; Pneumonia; Precision medicine; Procalcitonin; Procalcitonin - genetics; Procalcitonin - metabolism; Prognosis; Proteins; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Respiratory diseases; Respiratory Tract Infections - epidemiology; Respiratory Tract Infections - etiology; Respiratory Tract Infections - metabolism; Respiratory Tract Infections - pathology; Retrospective Studies; ROC Curve; Sensitivity; Sepsis; TNF-Related Apoptosis-Inducing Ligand - genetics; TNF-Related Apoptosis-Inducing Ligand - metabolism; United States - epidemiology; Veterans; Viral infections; Virus Diseases - complications; Virus Diseases - diagnosis; Virus Diseases - virology; Viruses - isolation & purification; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0261385

Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). 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. 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. A gene expression signature was the most accurate host response strategy for classifying subjects with bacterial, viral, or non-infectious ARI.