Background Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease's complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques. Results We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical

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... s assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes. Conclusions Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP. Trial registration Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628.