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Metatranscriptomics identifies pathogens and host responses associated with acute sinusitis in children

Abstract: Acute sinusitis (AS) is a frequent cause of antibiotic prescriptions in children. Distinguishing bacterial AS from common viral upper respiratory infections is crucial to prevent unnecessary antibiotic use. We performed RNA-seq of nasopharyngeal samples from 221 children with AS to better understand the etiology of AS and the impact of bacterial and viral infections on host immune responses. Metatranscriptomics detected three AS-associated bacterial pathogens with 87%/81% sensitivity/specificity (sens/spec) compared to culture, and 12 respiratory viruses with 86%/92% sens/spec compared to qRT-PCR. Metatranscriptomics also detected 22 additional pathogens not tested for in the clinical panel, and facilitated assembly of 205 viral genomes including new strains of coronaviruses, respiratory syncytial virus, and enterovirus D68. Lastly, metatranscriptomic analysis identified distinct host immune responses in individuals with bacterial versus viral infections. Our study demonstrates the power of metatranscriptomics for comprehensive analysis of AS etiology, and reveals host responses that could enable new diagnostic approaches.