Clinical, virological and immunological features from patients infected with re-emergent avian-origin human H7N9 influenza disease of varying severity in Guangdong province.
BACKGROUND
The second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region.


METHODS
Five patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery.


RESULTS
Four patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/β, IL-1β and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%).


CONCLUSIONS
Expectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Zi Feng
ZF
Yang
Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Chris Ka Pun
CK
Mok
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Xiao Qing
XQ
Liu
Health quarantine (BSL-3) Lab, Guangdong Inspection and Quarantine Technology Center, Guangzhou, China.
Xiao Bo
XB
Li
Guangdong Center for Disease Control and Prevention, Guangzhou, China.
Jian Feng
JF
He
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Wen Da
WD
Guan
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Yong Hao
YH
Xu
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Wei Qi
WQ
Pan
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Li Yan
LY
Chen
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Yong Ping
YP
Lin
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Shi Guan
SG
Wu
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Si Hua
SH
Pan
Health quarantine (BSL-3) Lab, Guangdong Inspection and Quarantine Technology Center, Guangzhou, China.
Ji Cheng
JC
Huang
Health quarantine (BSL-3) Lab, Guangdong Inspection and Quarantine Technology Center, Guangzhou, China.
Guo Yun
GY
Ding
Health quarantine (BSL-3) Lab, Guangdong Inspection and Quarantine Technology Center, Guangzhou, China.
Kui
K
Zheng
Guangdong Center for Disease Control and Prevention, Guangzhou, China.
Chang Wen
CW
Ke
Guangdong Center for Disease Control and Prevention, Guangzhou, China.
Jin Yan
JY
Lin
Guangdong Center for Disease Control and Prevention, Guangzhou, China.
Yong Hui
YH
Zhang
Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Horace Hok Yeung
HH
Lee
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Wen Kuan
WK
Liu
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Chun Guang
CG
Yang
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Rong
R
Zhou
Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Joseph Sriyal Malik
JS
Peiris
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Yi Min
YM
Li
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Rong Chang
RC
Chen
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Ling
L
Chen
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Nan Shan
NS
Zhong
D000328:Adult; D000368:Aged; D002681:China / Q000453:epidemiology; D021821:Communicable Diseases, Emerging; D016207:Cytokines / Q000097:blood; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000145:classification / Q000235:genetics; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D065288:Serogroup; D012720:Severity of Illness Index; D019562:Viral Load
D016207:Cytokines