title: Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients.
abstract: A novel influenza A (H7N9) virus of avian origin emerged in eastern China in the spring of 2013. This virus causes severe disease in humans, including acute and often lethal respiratory failure. As of January 2014, 275 cases of H7N9-infected patients had been reported, highlighting the urgency of identifying biomarkers for predicting disease severity and fatal outcomes. Here, we show that plasma levels of angiotensin II, a major regulatory peptide of the renin-angiotensin system, are markedly elevated in H7N9 patients and are associated with disease progression. Moreover, the sustained high levels of angiotensin II in these patients are strongly correlated with mortality. The predictive value of angiotensin II is higher than that of C-reactive protein and some clinical parameters such as the PaO2/FiO2 ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen). Our findings indicate that angiotensin II is a biomarker for lethality in flu infections.
authors.affiliation: 1] State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China [2].
authors.forename: Fengming
authors.initials: F
authors.lastname: Huang
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China [3].
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: 1] State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China [2].
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zou
authors.affiliation: 1] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China [2] National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China [3].
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: 1] Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, China [2].
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.affiliation: 1] Center for Translational Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China [2] Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China [3].
authors.forename: Shuyang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Hangzhou Center for Disease Control and Prevention, Hangzhou 310021, China.
authors.forename: Jingcao
authors.initials: J
authors.lastname: Pan
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Bao
authors.affiliation: Children's Hospital Affiliated with Fudan University, Shanghai 200032, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial, Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Xiao
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Guirong
authors.initials: G
authors.lastname: Qian
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Hu
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Huandi
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Jindong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Hainv
authors.initials: H
authors.lastname: Gao
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Shigui
authors.initials: S
authors.lastname: Yang
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Shufa
authors.initials: S
authors.lastname: Zheng
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Jiezuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Diao
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Hongcui
authors.initials: H
authors.lastname: Cao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Tan
authors.affiliation: 1] Center for Translational Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China [2] Clinical Biobank, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Yicong
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: 1] Center for Translational Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China [2] Clinical Biobank, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, Vienna A-1030, Austria.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.affiliation: 1] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China [2] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China [3] National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China [4] Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: 1] State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Tsinghua University, Beijing 100005, China [2] Center for Translational Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Jiang
authors.affiliation: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000097:blood* / Q000401:mortality* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019562:Viral Load
chemical_list: D015415:Biomarkers; D000804:Angiotensin II; D002097:C-Reactive Protein