Utilizing Metagenomic Next-Generation Sequencing (mNGS) for Rapid Pathogen Identification and to Inform Clinical Decision-Making: Results from a Large Real-World Cohort

INTRODUCTION: Clinical metagenomic next-generation sequencing (mNGS) has proven to be a powerful diagnostic tool in pathogen detection. However, its clinical utility has not been thoroughly evaluated. METHODS: In this single-center prospective study at the First Affiliated Hospital of Soochow University, a total of 228 samples from 215 patients suspected of having acute or chronic infections between June 2018 and December 2018 were studied. Samples that met the mNGS quality control (QC) criteria (N = 201) were simultaneously analyzed using conventional tests (CTs), including multiple clinical microbiological tests and real-time PCR (if applicable). RESULTS: Pathogen detection results of mNGS in the 201 QC-passed samples were compared to CTs and exhibited a sensitivity of 98.8%, specificity of 38.5%, and accuracy of 87.1%. Specifically, 109 out of 160 (68.1%) CT+/mNGS+ samples exhibited concordant results at the species/genus level, 25 samples (15.6%) showed overlapping results, while the remaining 26 samples (16.3%) had discordant results between the CT and mNGS assays. In addition, mNGS could identify pathogens at the species level, whereas only the genera of some pathogens could be identified by CT. In this cohort, mNGS results were used to guide treatment plans in 24 out of 41 cases that had available follow-up information, and the symptoms were improved in over 70% (17/24) of them. CONCLUSION: Our data demonstrated the analytic performance of our mNGS pipeline for pathogen detection using a large clinical cohort and strongly supports the notion that in clinical practice, mNGS represents a valuable supplementary tool to CTs to rapidly determine etiological factors of various types of infection and to guide treatment decision-making. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40121-023-00790-5.