Clinical application and impact of metagenomic next-generation sequencing for the diagnosis of infectious diseases in severely immunocompromised pediatric patients

BACKGROUND: Accurate and rapid microbiological diagnosis is essential for the identification and management of critically ill children experiencing immunocompromised (ICH) conditions. Metagenomic next-generation sequencing (mNGS) has shown promising applications in diagnosing infectious diseases in adults; however, its performance in critically ill pediatric infections remains elusive. We aimed to evaluate the performance of mNGS, compared with that of conventional microbiological tests (CMT) as a front-line diagnostic tool for pediatric intensive care unit (PICU) patients, and assess its clinical impact. METHODS: In this retrospectively study, a total of 179 samples including blood, sputum or cerebrospinal fluid etc. from 97 children, categorized as ICH or immunocompetent (ICO), were included. The positive detection rate and diagnostic performance (sensitivity, specificity) of mNGS and CMT were compared. The clinical impact of mNGS was assessed on its influence on diagnosis and treatment decisions. RESULTS: mNGS demonstrated a significantly higher positive rate than CMT (72.63% vs. 55.31%, P < 0.001), particularly in sputum and cerebrospinal fluid (CSF) samples, among both ICH and ICO samples. Samples from ICH patients exhibited a relatively higher positive rate and yielded more microbes detections than ICO samples with both methods. The sensitivity of mNGS assay was 91.34%, significantly outperforming CMT (73.23%, P < 0.001). The specificity of mNGS was 73.08%, relatively lower than that of CMT (88.46%, P < 0.05). Specific to ICH and ICO, mNGS showed significantly higher sensitivity than CMT (ICH: 94.94% vs. 81.01%, P < 0.01; ICO:85.42% vs. 60.42%, P < 0.01). Regarding clinical impact, mNGS had a positive impact on diagnosis in 66.0% patients, with a significantly higher proportion of positive impacts observed in ICH samples compared to ICO samples (P < 0.05). CONCLUSIONS: mNGS exhibited superior diagnostic performance compared to CMT for diagnosing infections in critically ill children. More than half (66.0%) of mNGS tests resulted in a positive clinical impact on diagnosis and treatment, particularly among ICH patients.