Comparison between human infections caused by highly and low pathogenic H7N9 avian influenza viruses in Wave Five: Clinical and virological findings

Yang Yang; Gary Wong; Liuqing Yang; Shuguang Tan; Jianming Li; Bing Bai; Zhixiang Xu; Hong Li; Wen Xu; Xiaonan Zhao; Chuansong Quan; Haixia Zheng; William J Liu; Wenjun Liu; Lei Liu; Yingxia Liu; Yuhai Bi; George F Gao

doi:10.1016/j.jinf.2019.01.005

Comparison between human infections caused by highly and low pathogenic H7N9 avian influenza viruses in Wave Five: Clinical and virological findings

J Infect. 2019 Mar;78(3):241-248. doi: 10.1016/j.jinf.2019.01.005. Epub 2019 Jan 18.

Authors

Yang Yang¹, Gary Wong², Liuqing Yang³, Shuguang Tan⁴, Jianming Li³, Bing Bai⁵, Zhixiang Xu³, Hong Li⁶, Wen Xu⁶, Xiaonan Zhao⁶, Chuansong Quan⁷, Haixia Zheng³, William J Liu⁷, Wenjun Liu⁴, Lei Liu³, Yingxia Liu⁸, Yuhai Bi⁹, George F Gao¹⁰

Affiliations

¹ Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, State Key Discipline of Infectious Disease, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
² Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; Département de microbiologie-infectiologie et d'immunologie, Université Laval, Québec City G1V 0A6, Canada.
³ Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, State Key Discipline of Infectious Disease, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen 518112, China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
⁵ Department of Infectious Diseases and Shenzhen Key Lab for Endogenous Infection, Shenzhen Nanshan Hospital of Shenzhen University, Shenzhen 518000, China.
⁶ Yunnan Center for Disease Control and Prevention, Kunming 650022, China.
⁷ National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
⁸ Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, State Key Discipline of Infectious Disease, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen 518112, China; University of Chinese Academy of Sciences Medical School, Chinese Academy of Sciences, Beijing 101408, China. Electronic address: yingxialiu@hotmail.com.
⁹ Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, State Key Discipline of Infectious Disease, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China. Electronic address: beeyh@im.ac.cn.
¹⁰ Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, State Key Discipline of Infectious Disease, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China; University of Chinese Academy of Sciences Medical School, Chinese Academy of Sciences, Beijing 101408, China. Electronic address: gaof@im.ac.cn.

PMID: 30664912
DOI: 10.1016/j.jinf.2019.01.005

Abstract

Objective: The newly emerged highly pathogenic (HP) H7N9 avian influenza virus during Wave Five has caused 28 human infections, while differences in disease severity between low pathogenic (LP)- and HP-H7N9 human infections remain unclear.

Methods: Clinical data, concentrations of serum cytokines, dynamics of virus shedding and PaO₂/FiO₂ from patients infected with LP-H7N9 (n = 7, LP group) and HP-H7N9 (n = 5, HP group) viruses during Wave Five were compared. In addition, critical mutations associated with H7N9 virulence in mammal/human were analyzed.

Results: Lymphopenia, elevated aspartate aminotransferase, alanine aminotransferase, C-reactive protein and lactate dehydrogenase were common features, with higher incidences of leukopenia and thrombocytopenia in the LP group. The acute phase of both groups was accompanied with elevated cytokines associated with disease severity, including MIF, MCP-1 and IP-10. Diffuse exudation of the lungs and consolidation were observed from all patients. The dynamics of virus shedding and PaO₂/FiO₂ were similar between both groups. Notably, a higher prevalence of neuraminidase inhibitors (NAIs) resistance in the HP-H7N9 virus was found.

Conclusions: Our results indicate that this newly emerged HP-H7N9 virus caused similar disease severity in humans compared with LP-H7N9 virus, while higher case fatality rate and prevalence of NAI-resistance in human HP-H7N9 infections were of great concern.

Keywords: Avian influenza virus (AIV); Clinical comparison; H7N9; Highly pathogenic (HP); Low pathogenic (LP); Neuraminidase inhibitors (NAIs) resistance; Wave Five.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Animals
Antiviral Agents / pharmacology
Chickens
Child
Child, Preschool
China / epidemiology
Cytokines / blood
Drug Resistance, Viral
Female
Humans
Influenza A Virus, H7N9 Subtype / drug effects
Influenza A Virus, H7N9 Subtype / genetics
Influenza A Virus, H7N9 Subtype / pathogenicity*
Influenza in Birds / epidemiology
Influenza in Birds / virology*
Influenza, Human / epidemiology
Influenza, Human / mortality
Influenza, Human / virology*
Male
Middle Aged
Mortality
Severity of Illness Index*
Virulence / genetics
Young Adult

Substances

Antiviral Agents
Cytokines