Clinical Application and Evaluation of Metagenomic Next-Generation Sequencing for Lower Respiratory Tract Infections and Human Tumor Screening

Jinbao Huang,1,* Heng Weng,1,* Ling Ye,1 Meiqin Jiang,1 Yangyu Li,2 Hongyan Li3 1Department of Respiratory Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China; 2Department of Clinical Laboratory Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China; 3Department of Critical Care Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongyan Li, Department of Critical Care Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, No. 602 Middle 817 Road, Taijiang District, Fuzhou, 350004, People’s Republic of China, Email fjsrmyylhy@163.comBackground: To evaluate the clinical value of metagenomic next-generation sequencing (mNGS) in screening of lower respiratory tract infections (LRTIs) and human tumors.Methods: Human samples included bronchoalveolar lavage fluid (BALF), sputum, lung biopsy tissue, and peripheral blood from 188 patients who were admitted to our hospital between January 2020 and September 2022 were analyzed using mNGS for simultaneous pathogen and chromosome copy number variation (CNV) detection. Traditional microbial culture and comprehensive microbial test (CMT) were also conducted. The diagnostic efficiencies of the three methods (mNGS, traditional culture, and CMT groups) were compared.Results: Among the 188 patients, 149 (79.3%) were in the LRTIs group and 39 (20.7%) were in the non-LRTIs group. The diagnostic sensitivity and accuracy of the mNGS group were higher than those of the traditional culture and CMT groups (P < 0.001; P < 0.001; P < 0.001; P < 0.001), and the specificity was higher than that of the CMT group (P = 0.039) but lower than that of the traditional culture group (P = 0.006). The positive predictive values of the mNGS and traditional culture groups were higher than that of the CMT group (P = 0.004; P = 0.011). The negative predictive value of the mNGS group was higher than that of the CMT group (P = 0.003). In addition, all samples were subjected to simultaneous chromosome CNV detection, and 8% (15/188) were positive for CNV. Of the 15 patients, 10 were initially misdiagnosed as non-neoplastic diseases, with a misdiagnosis rate of 66.7% (10/15). The BALF CNV test was performed on 13 patients diagnosed with primary or metastatic lung cancer, with a positivity rate of 38.5%.Conclusion: The sensitivity and accuracy of pathogen diagnosis using mNGS were better than those of traditional culture and CMT. CNV detection is an important auxiliary diagnostic tool for cancer, particularly for screening occult tumors. Keywords: metagenomics, next-generation sequencing, respiratory infectious diseases, pathogen diagnosis, genomic instability