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Peer-reviewedCC BY 4.0Microbiology Spectrum

A nationwide study of pathogens in hospitalized patients with lower respiratory tract infections by metagenomic next-generation sequencing

15 more authors
6 affiliations
  1. 1Center for Molecular Diagnosis and Precision Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
  2. 2Department of Medical Genetics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
  3. 3Jiangxi Provincial Center for Advanced Diagnostic Technology and Precision Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
  4. 4Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
  5. 5Medical Department, Hangzhou, Pan-omics Biotechnology Co., Ltd., Hangzhou, Zhejiang, China
  6. 6School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, China

Abstract

Lower respiratory tract infections remain a major cause of morbidity and mortality, yet timely etiologic diagnosis is difficult because of the breadth of possible pathogens and the limitations of conventional microbiological tests. We retrospectively analyzed 30,819 clinical specimens from 27,507 hospitalized patients with lower respiratory tract infections across 31 provincial-level regions in mainland China from April 2019 to May 2025 to characterize the pathogen spectrum detected by metagenomic sequencing. In total, 323 pathogens were identified, 33.74% of which were fastidious or unculturable microorganisms. The overall positivity rate was 80.12%, and 65.48% of positive specimens showed co-detections. The top 20, 50, 100, 150, and 200 pathogens accounted for 70.17%, 87.56%, 95.59%, 98.18%, and 99.26% of all reported pathogens, respectively. Pathogen distributions differed by age, season, geography, clinical department, and comorbidity, and several epidemiological shifts were observed across the pre-pandemic, pandemic, and post-restriction periods, including persistent declines in Streptococcus pneumoniae and Chlamydia psittaci. These findings demonstrate the breadth of organisms detected by metagenomic sequencing in routine practice and support its value for broad etiologic assessment of lower respiratory tract infections.

IMPORTANCE: Lower respiratory tract infections are frequently managed before the etiologic agent is established because many bacteria, viruses, fungi, and other organisms can produce similar clinical syndromes, and conventional tests do not capture this diversity well. By analyzing more than 30,000 real-world specimens from hospitalized patients across mainland China, this study shows which organisms are most often detected by metagenomic sequencing, how frequently mixed detections occur, and how pathogen patterns vary by age, geography, season, clinical setting, and the 2019 coronavirus disease period. These findings clarify where broad-range sequencing can add value for microbiology, surveillance, and future targeted panel design.

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BibTeX
@article{gong2026nationwide,
  title = {{A nationwide study of pathogens in hospitalized patients with lower respiratory tract infections by metagenomic next-generation sequencing}},
  author = {Tian Gong and Qiong Liu and Yiqi Wan and Xuan Zhang and Chao Liu and Xiaojia Wang and Ling Cao and Jing Li and Liang Zhang and Biaoxian Li and Chensong Sun and Yaping Guo and Shupeng Yin and Xiumei Xu and Hao Chen and Zhiting Xie and Manli Gong and Haiyan Lin and Xiao Lei and Ting Zeng and Xinyi Ren and Shaomin Zou and Sufeng Zhang and Qifei Peng and Aling Gao and Jun Wang and Chengsheng Zhang},
  journal = {Microbiology Spectrum},
  year = {2026},
  month = sep,
  doi = {10.1128/spectrum.01746-26},
  url = {https://doi.org/10.1128/spectrum.01746-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A nationwide study of pathogens in hospitalized patients with lower respiratory tract infections by metagenomic next-generation sequencing
AU  - Tian Gong
AU  - Qiong Liu
AU  - Yiqi Wan
AU  - Xuan Zhang
AU  - Chao Liu
AU  - Xiaojia Wang
AU  - Ling Cao
AU  - Jing Li
AU  - Liang Zhang
AU  - Biaoxian Li
AU  - Chensong Sun
AU  - Yaping Guo
AU  - Shupeng Yin
AU  - Xiumei Xu
AU  - Hao Chen
AU  - Zhiting Xie
AU  - Manli Gong
AU  - Haiyan Lin
AU  - Xiao Lei
AU  - Ting Zeng
AU  - Xinyi Ren
AU  - Shaomin Zou
AU  - Sufeng Zhang
AU  - Qifei Peng
AU  - Aling Gao
AU  - Jun Wang
AU  - Chengsheng Zhang
PY  - 2026
DA  - 2026/09/23
JO  - Microbiology Spectrum
DO  - 10.1128/spectrum.01746-26
UR  - https://doi.org/10.1128/spectrum.01746-26
AB  - Lower respiratory tract infections remain a major cause of morbidity and mortality, yet timely etiologic diagnosis is difficult because of the breadth of possible pathogens and the limitations of conventional microbiological tests. We retrospectively analyzed 30,819 clinical specimens from 27,507 hospitalized patients with lower respiratory tract infections across 31 provincial-level regions in mainland China from April 2019 to May 2025 to characterize the pathogen spectrum detected by metagenomic sequencing. In total, 323 pathogens were identified, 33.74% of which were fastidious or unculturable microorganisms. The overall positivity rate was 80.12%, and 65.48% of positive specimens showed co-detections. The top 20, 50, 100, 150, and 200 pathogens accounted for 70.17%, 87.56%, 95.59%, 98.18%, and 99.26% of all reported pathogens, respectively. Pathogen distributions differed by age, season, geography, clinical department, and comorbidity, and several epidemiological shifts were observed across the pre-pandemic, pandemic, and post-restriction periods, including persistent declines in Streptococcus pneumoniae and Chlamydia psittaci. These findings demonstrate the breadth of organisms detected by metagenomic sequencing in routine practice and support its value for broad etiologic assessment of lower respiratory tract infections.  IMPORTANCE: Lower respiratory tract infections are frequently managed before the etiologic agent is established because many bacteria, viruses, fungi, and other organisms can produce similar clinical syndromes, and conventional tests do not capture this diversity well. By analyzing more than 30,000 real-world specimens from hospitalized patients across mainland China, this study shows which organisms are most often detected by metagenomic sequencing, how frequently mixed detections occur, and how pathogen patterns vary by age, geography, season, clinical setting, and the 2019 coronavirus disease period. These findings clarify where broad-range sequencing can add value for microbiology, surveillance, and future targeted panel design.
SN  - 2165-0497
ER  -