Metagenomic Next-generation Sequencing Indicates More Precise Pathogens in patients with pulmonary infection: a retrospective study

Abstract Background: Timely identification of causative pathogens is always an important link for the diagnosis and treat for pulmonary infection. As a novel approach to detect the pathogens, metagenomic next-generation sequencing (mNGS) can directly sequence the nucleic acid of specimens, providing a wide range of microbial profiles. The purpose of this study is to evaluate the diagnostic performance of mNGS of bronchoalveolar lavage fluid (BALF) in patients suspected with pulmonary infection.Methods: From April 2019 to July 2021, 502 patients with suspected pneumonia undergoing both mNGS of BALF and conventional microbiological tests (CMTs) were classified into different groups based on the comorbidities. The diagnostic performance was compared between mNGS and CMTs. Clinical comprehensive analysis was regarded as reference standard. Result: The diagnostic accuracy and sensitivity of mNGS were 74.9% (95% confidence interval [CI], 71.7-78.7%) and 72.5% (95% CI, 68.2-76.8%) respectively, outperformed those of CMTs (36.2% for diagnostic accuracy, 25.4% for sensitivity). In most of the pathogens, the detection rate of mNGS was higher than CMTs. Polymicrobial infections most often occurred in immunocompromised group (22.1%), followed by other comorbidities group (22.1% vs 13.3%, p= 0.13) and bronchiectasis group (22.1% vs 9.7%, p= 0.018). Only 2.3% (95%CI, 0.3%-4.4%) patients developed polymicrobial infection in simple pulmonary infection group. Besides, the spectrums of pathogens also varied in different groups. Importantly, the positive predictive values (PPVs) of mNGS were observed discrepant in different pathogens: 94.9% (95%CI 89.1-100%) for Mycobacterium tuberculosis, 86.2% (95%CI,72.9-99.6%) for Chlamydia psittaci, 86.0% (95%CI, 76.0-96.0%) for Aspergillus, and 67.6% (95%CI, 51.1-84.2%) for Non-mycobacterium tuberculosis, 67.3% (95%,54.1-80.5%) for Pneumocystis jeroveci; as for bacteria, the PPVs also show differences in different types of bacteria. Conclusion: mNGS of BALF can highly enhance the accuracy and detection rate of pathogens in patients with pulmonary infection. Besides, the comorbidities and the types of pathogens should be taken into consideration when interpreting the report of mNGS.