Metatranscriptomic profiling reveals pathogen and host response signatures of pediatric acute sinusitis and upper respiratory infection.

Summary

Untargeted RNA-seq of nasopharyngeal samples from 221 children achieved high sensitivity/specificity for common bacterial and viral pathogens versus culture/qRT‑PCR, detected additional untested pathogens, and reconstructed 196 viral genomes. Host-expression signatures distinguished bacterial from viral infections, nominating hundreds of diagnostic biomarker candidates.

Key Findings

• RNA-seq showed 87%/81% sensitivity/specificity for three AS‑associated bacteria and 86%/92% for 12 respiratory viruses vs clinical tests.
• Detected 22 additional pathogens not clinically tested and identified plausible agents in 58% of otherwise negative cases.
• Reconstructed 196 viral genomes (including novel strains) and defined host-response signatures distinguishing bacterial vs viral infections.

Clinical Implications

While not yet ready for routine care, metatranscriptomic diagnostics could reduce unnecessary antibiotics by resolving viral vs bacterial etiologies; host-response markers may be translated into rapid assays.

Limitations

• Single time‑point sampling; no prospective clinical utility assessment or impact on antibiotic prescribing
• Cost, turnaround time, and bioinformatics infrastructure remain barriers for routine deployment

Future Directions

Prospective validation in pragmatic trials linking RNA‑seq outputs to antibiotic decisions; translate host‑response gene sets into rapid point‑of‑care assays.