Clinical Utility of Metagenomic Next-Generation Sequencing in Diagnosing Central Nervous System Infections in Hematopoietic Stem Cell Transplant Recipients: A Retrospective and Prospective Cohort Study

Background: Diagnosing central nervous system infections (CNSI) in hematopoietic stem cell transplant (HSCT) recipients remains challenging due to nonspecific presentations and low sensitivity of conventional microbiological methods. Methods: This study evaluated the clinical utility of cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) in 127 HSCT recipients (87 retrospective, 40 prospective) from Peking University People's Hospital. Pathogens detected by mNGS and conventional methods were validated via Sanger sequencing. Results: mNGS identified 20 pathogen-positive samples (19 confirmed by sequencing), while conventional methods detected none. mNGS demonstrated 82.6% sensitivity and 99.0% specificity for CNSI diagnosis, with sensitivity rising to 100.0% when combined with conventional approaches. Notably, mNGS excelled in detecting viral pathogens, particularly in allogeneic HSCT recipients. Conclusion: Our findings advocate for the integration of mNGS into the diagnostic algorithm for CNSI, especially in immunocompromised hosts. This approach enables earlier and more precise pathogen identification, which has the potential to streamline antimicrobial therapy and improve clinical management. To maximize its benefit and ensure reliable interpretation, mNGS results should be correlated with comprehensive clinical and paraclinical data. Further prospective studies are warranted to validate its impact on therapeutic decision-making and patient prognosis.