Nanopore-based metagenomic sequencing for the rapid and precise detection of pathogens among immunocompromised cancer patients with suspected infections

Cancer patients are at high risk of infections and infection-related mortality; thereby, prompt diagnosis and precise anti-infectives treatment are critical. This study aimed to evaluate the performance of nanopore amplicon sequencing in identifying microbial agents among immunocompromised cancer patients with suspected infections. This prospective study enlisted 56 immunocompromised cancer patients with suspected infections. Their body fluid samples such as sputum and blood were collected, and potential microbial agents were detected in parallel by nanopore amplicon sequencing and the conventional culture method. Among the 56 body fluid samples, 47 (83.9%) samples were identified to have at least one pathogen by nanopore amplicon sequencing, but only 25 (44.6%) samples exhibited a positive finding by culture. Among 31 culture-negative samples, nanopore amplicon sequencing successfully detected pathogens in 22 samples (71.0%). Nanopore amplicon sequencing showed a higher sensitivity in pathogen detection than that of the conventional culture method (83.9% vs. 44.6%, P<0.001), and this advantage both existed in blood samples (38.5% vs. 0%, P=0.039) and non-blood samples (97.7% vs. 58.1%, P<0.001). Compared with the culture method, nanopore amplicon sequencing illustrated more samples with bacterial infections (P<0.001), infections from fastidious pathogens (P=0.006), and co-infections (P<0.001). The mean turnaround time for nanopore amplicon sequencing was about 17.5 hours, which was shorter than that of the conventional culture assay. This study suggested nanopore amplicon sequencing as a rapid and precise method for detecting pathogens among immunocompromised cancer patients with suspected infections. The novel and high-sensitive method will improve the outcomes of immunocompromised cancer patients by facilitating the prompt diagnosis of infections and precise anti-infectives treatment.