Clinical Efficacy and Diagnostic Value of Metagenomic Next-Generation Sequencing for Pathogen Detection in Patients with Suspected Infectious Diseases: A Retrospective Study from a Large Tertiary Hospital

Yang-Hua Xiao,1,2 Mei-Fang Liu,1 Hongwen Wu,1,3 De-Rong Xu,1 Rui Zhao1 1Department of Clinical Laboratory, Medical Center for Burn and Plastic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2School of Public Health, Nanchang University, Nanchang, People’s Republic of China; 3Department of Medical Instruments, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: De-Rong Xu; Rui Zhao, Email xudr@ncu.edu.cn; zhaoruisc@163.comPurpose: Metagenomic next-generation sequencing (mNGS) is a powerful yet unbiased method to identify pathogens in suspected infections. However, little is known about its clinical effectiveness. The present study aimed to assess the efficacy of mNGS in routine clinical practice.Patients and Methods: In this single-center retrospective cohort study, 518 patients with suspected infectious diseases were assessed for inclusion. Among them, each patient had undergone mNGS testing; 407 patients had undergone both microbial culture and mNGS testing. The result of mNGS testing was compared to microbial culture performed concurrently. The diagnostic performance of mNGS was evaluated using the comprehensive clinical diagnosis as the reference standard.Results: There was a significant difference in the positive detection rates of pathogens between mNGS and culture (331/407, 81.3% vs 79/407, 19.4%, P < 0.001). The sensitivity of mNGS was much higher than the culture method (79.5% vs 21.3%, P < 0.001), especially in sample types of sputum and bronchoalveolar lavage fluid (BALF). Notably, the sensitivity of blood mNGS was relatively lower than other sample types (67.4% vs 88.9– 93.8%). Pathogen cfDNA load based on standardized stringently mapped read number at the species level of microorganisms (SDSMRN) was significantly lower in blood than in other sample types from the same patient (P = 0.0003). Importantly, mNGS directly led to a change of