title: A case report demonstrating the utility of next generation sequencing in analyzing serial samples from the lung following an infection with influenza A (H7N9) virus.
abstract: BACKGROUND
  Bacterial pneumonia is a well-recognized sequela of patient suffering from influenza, and a key factor, with cytokine dysregulation, that contribute to severe disease and mortality.
  
  
  OBJECTIVE
  To obtain a comprehensive assessment of lung microbial community dynamics in a fatal influenza H7N9 case during the whole clinical course, we undertook a longitudinal study.
  
  
  METHODS
  Serial bronchoalveolar lavage fluid samples were collected from a H7N9 patient after illness onset, and the microbiome was characterized by using next-generation sequencing and microbiological approaches. Furthermore, the kinetics of circulating cytokine storms related to viral and secondary bacterial infection were analyzed.
  
  
  RESULTS
  Within complex and dynamic communities, the lung microbiome with H7N9 infection were dominated by gram-negative bacteria, Acinetobacter baumannii after the viral invasion and during the whole clinical course. Sputum and blood culture confirmed the secondary bacterial infection with multidrug-resistant A. baumannii 9 days later. The dynamics of the bacterial infection with carbapenem-resistant A. baumannii correlated with antibiotic therapy. Our observations also indicated that sustained high levels of host inflammatory factors, consisting of a set of distinct cytokines associated with disease stage, may contribute to disease progression and death.
  
  
  CONCLUSIONS
  This study demonstrates an initial attempt to explore the dynamic microbiome involved inH7N9 infection and its response to antimicrobial therapy, as well as host cytokine response to infection by using next-generation sequencing. These type of investigations with longitudinal follow-up to understand dynamics of microbial community and cytokines involved in lung infection may provide opportunities for development and optimization of targeted antimicrobial therapy and even new therapeutic strategies.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Hu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China; Centre of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China; National Clinical Research Centre for Respiratory Disease, Beijing, China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Haoxiang
authors.initials: H
authors.lastname: Su
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Electronic address: haiyingbj@ipbcams.ac.cn.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China; Centre of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China; National Clinical Research Centre for Respiratory Disease, Beijing, China. Electronic address: caobin_ben@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address: zdsys@vip.sina.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology / Q000821:virology; D040981:Acinetobacter baumannii / Q000235:genetics / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D060085:Coinfection / Q000382:microbiology / Q000401:mortality / Q000821:virology; D016207:Cytokines / Q000097:blood; D017809:Fatal Outcome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000302:isolation & purification*; D007251:Influenza, Human / Q000150:complications / Q000175:diagnosis / Q000821:virology*; D008137:Longitudinal Studies; D008168:Lung / Q000382:microbiology* / Q000821:virology*; D064307:Microbiota; D008875:Middle Aged; D013183:Sputum / Q000821:virology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines
keywords: Diagnostic value; Influenza A (H7N9) virus; Lung infection; Next generation sequencing