A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations

Journal article

Limited sensitivity and specificity of current diagnostics lead to the erroneous prescription of antibiotics. Host-response-based diagnostics could address these challenges. However, using 4,200 samples across 69 blood transcriptome datasets from 20 countries from patients with bacterial or viral infections representing a broad spectrum of biological, clinical, and technical heterogeneity, we show current host-response-based gene signatures have lower accuracy to distinguish intracellular bacterial infections from viral infections than extracellular bacterial infections. Using these 69 datasets, we identify an 8-gene signature to distinguish intracellular or extracellular bacterial infections from viral infections with an area under the receiver operating characteristic curve (AUROC) > 0.91 (85.9% specificity and 90.2% sensitivity). In prospective cohorts from Nepal and Laos, the 8-gene classifier distinguished bacterial infections from viral infections with an AUROC of 0.94 (87.9% specificity and 91% sensitivity). The 8-gene signature meets the target product profile proposed by the World Health Organization and others for distinguishing bacterial and viral infections.

Authors: Rao, AM; Popper, SJ; Gupta, S; Davong, V; Vaidya, K

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell Reports Medicine
• Volume: 3
• Issue: 12
• Article number: 100842
• Publication date: 2022-12-20
• Acceptance date: 2022-11-09
• DOI: 10.1016/j.xcrm.2022.100842
• EISSN: 2666-3791
• Pmid: 36543117
• Language: English
• Keywords: transcriptome; virus diseases; sensitivity and specificity; infectious disease diagnosis; public health; bacterial infections; antimicrobial resistance; FFR; host response; prospective studies; gene expression; bacterial vs. viral diagnosis; point-of-care diagnostics; global health