Ziyang Li ¹ Tan Li ¹ Jialiang Zhang ¹ Qichen Long ¹ Zhiyang Chen ¹ Zhongyuan Xiang ¹ Weimin Wu ¹ Zhe Guo ¹ Huifang Liu ² Bingxue Hu ² Bin Yang ² Min Hu ^1*

• ¹ Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
• ² Vision Medicals Co., Ltd, Guangzhou, China

Background: Metagenomic next⁃generation sequencing (mNGS) has been widely reported to identify pathogens in infectious diseases (IDs). In this work, we intended to investigate the diagnostic value and clinical acceptance of paired-samples mNGS as compared culture method. Methods: A total of 361 patients with suspected infection were retrospectively included. As reference to the clinical diagnosis, we compared the diagnostic performance and clinical acceptance in pathogen detection between mNGS and culture tests. Besides, the pathogen concordance of paired blood and respiratory tract (RT) samples in mNGS assay was investigated. Results: Among 511 samples, 62.04% were shown to be pathogen positive by mNGS, and that for clinical diagnosis was 51.86% (265/511). When compared to culture assay (n=428), mNGS had a significantly higher positivity rate (51.87% vs 33.18%). As reference to the clinical diagnosis, the sensitivity of mNGS outperformed than that of culture (89.08% vs 56.72%). Importantly, mNGS exhibited a significantly superior clinically accepted rate than culture. In addition, the mNGS result from 53 paired blood and RT samples showed that most pairs were pathogen positive by both blood and RT, with pathogens were largely to be partially matched. Conclusion: Through this large-scale study, we further illustrated that mNGS had superior sensitivity and clinically accepted rate than the traditional culture method in diagnosing infections. Moreover, blood and paired RT samples mostly shared partial-matched positive pathogens, especially for pathogens with abundant reads numbers in RT, indicating that both blood and RT mNGS can aid the identification of pathogens for respiratory system infection.