AUTHOR=Qian Yi-Yi , Wang Hong-Yu , Zhou Yang , Zhang Hao-Cheng , Zhu Yi-Min , Zhou Xian , Ying Yue , Cui Peng , Wu Hong-Long , Zhang Wen-Hong , Jin Jia-Lin , Ai Jing-Wen 

TITLE=Improving Pulmonary Infection Diagnosis with Metagenomic Next Generation Sequencing

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 10 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.567615

DOI=10.3389/fcimb.2020.567615

ISSN=2235-2988

ABSTRACT=Pulmonary infection is among the most common and important infectious diseases due to its high morbidity and mortality, especially in elder and immunocompromised population. However, due to the limitations in sensitivity and/or long turn-around time (TAT) of conventional diagnosis methods, pathogen detection and identification methods for pulmonary infection with higher diagnosis efficiency are in urgent need. In recent years, unbiased metagenomic next generation sequencing (mNGS) has been widely used in different types of infection for pathogen detection, especially for rare and newly discovered pathogens, showing better diagnosis performance over traditional methods. While there has been limited researches thoroughly exploring the application of mNGS in pulmonary infections, in this study we evaluated the diagnostic efficiency and clinical impacts of mNGS in this disease. A total of 100 respiratory samples were collected from patients diagnosed with pulmonary infection in Shanghai, China. Conventional methods, including culture and quick PCR panel analysis for respiratory tract viruses, and mNGS were used for the pathogen detection in respiratory samples. The differences in diagnosis yields between conventional methods and mNGS analysis demonstrated that: 1) mNGS had better sensitivity in the detection of pathogenic bacteria and fungi than traditional culture (95% [95/100] vs 54% [54/100]; p<0.001); 2) although mNGS had inferior sensitivity compared with PCR in virus diagnosis, in 15 cases it identified virus that failed being detected by conventional methods, particulally multiple subtypes of Human herpes virus; and 3) mNGS detected virus with genome coverage over 95% and sequencing depth over 100× also provided reliable phylogenetic and epidemic information. Besides, mNGS offered extra benefits, including shorter TAT. In conclusion, mNGS analysis facilitated fast pathogen detection with better diagnosis efficiency, contributing to prompt and accurate treatment of peripheral pulmonary infections. We highly recommend timely conduction of mNGS when infection of mixed or rare pathogens is considered, especially when the patients are immune-compromised or under severe condition that require timely treatment.