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
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
BGI PathoGenesis Pharmaceutical Technology Co., Ltd, BGI-Shenzhen, Shenzhen, China.
Front Cell Infect Microbiol. 2021 Jan 26;10:567615. doi: 10.3389/fcimb.2020.567615. eCollection 2020.
Pulmonary infections are among the most common and important infectious diseases due to their high morbidity and mortality, especially in older and immunocompromised individuals. However, due to the limitations in sensitivity and the long turn-around time (TAT) of conventional diagnostic methods, pathogen detection and identification methods for pulmonary infection with greater diagnostic efficiency are urgently needed. In recent years, unbiased metagenomic next generation sequencing (mNGS) has been widely used to detect different types of infectious pathogens, and is especially useful for the detection of rare and newly emergent pathogens, showing better diagnostic performance than traditional methods. There has been limited research exploring the application of mNGS for the diagnosis of pulmonary infections. In this study we evaluated the diagnostic efficiency and clinical impact of mNGS on pulmonary infections. A total of 100 respiratory samples were collected from patients diagnosed with pulmonary infection in Shanghai, China. Conventional methods, including culture and standard polymerase chain reaction (PCR) panel analysis for respiratory tract viruses, and mNGS were used for the pathogen detection in respiratory samples. The difference in the diagnostic yield between conventional methods and mNGS demonstrated that mNGS had higher sensitivity than traditional culture for the detection of pathogenic bacteria and fungi (95% vs 54%; p<0.001). Although mNGS had lower sensitivity than PCR for diagnosing viral infections, it identified 14 viral species that were not detected using conventional methods, including multiple subtypes of human herpesvirus. mNGS detected viruses with a genome coverage >95% and a sequencing depth >100× and provided reliable phylogenetic and epidemiological information. mNGS offered extra benefits, including a shorter TAT. As a complementary approach to conventional methods, mNGS could help improving the identification of respiratory infection agents. We recommend the timely use of mNGS when infection of mixed or rare pathogens is suspected, especially in immunocompromised individuals and or individuals with severe conditions that require urgent treatment.
肺部感染是最常见且重要的传染病之一，因其发病率和死亡率高，在老年人和免疫功能低下者中尤为如此。然而，由于传统诊断方法在敏感性和较长周转时间（TAT）方面存在局限性，迫切需要诊断效率更高的肺部感染病原体检测和鉴定方法。近年来，无偏宏基因组下一代测序（mNGS）已被广泛用于检测不同类型的感染性病原体，尤其对罕见和新出现病原体的检测很有用，显示出比传统方法更好的诊断性能。探索mNGS在肺部感染诊断中的应用的研究有限。在本研究中，我们评估了mNGS对肺部感染的诊断效率和临床影响。从中国上海被诊断为肺部感染的患者中总共收集了100份呼吸道样本。采用传统方法，包括培养和呼吸道病毒的标准聚合酶链反应（PCR）检测，以及mNGS对呼吸道样本中的病原体进行检测。传统方法和mNGS在诊断率上的差异表明，mNGS在检测病原菌和真菌方面比传统培养具有更高的敏感性（95%对54%；p<0.001）。虽然mNGS在诊断病毒感染方面比PCR敏感性低，但它鉴定出了14种用传统方法未检测到的病毒种类，包括人类疱疹病毒的多个亚型。mNGS检测到基因组覆盖率>95%且测序深度>100×的病毒，并提供了可靠的系统发育和流行病学信息。mNGS还有额外的优势，包括更短的周转时间。作为传统方法的补充手段，mNGS有助于提高呼吸道感染病原体的鉴定。我们建议在怀疑混合或罕见病原体感染时及时使用mNGS，特别是在免疫功能低下者和需要紧急治疗的重症患者中。
