Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease
Chunlan Song,
Yu Li,
Yonghong Zhou,
Lu Liang,
Lance Turtle,
Fang Wang,
Peng Wu,
Qi Qiu,
Jianli Yang,
Kai Wang,
Peng Cui,
Yibing Cheng,
Tianchen Zhang,
Chun Guo,
Mengyao Zeng,
Lu Long,
Malik Peiris,
Chongchen Zhou,
Benjamin J Cowling,
Hongjie Yu
Affiliations
Chunlan Song
Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China
Yu Li
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China
Yonghong Zhou
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Lu Liang
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Lance Turtle
NIHR Health Protection Research Unit for Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom; Tropical & Infectious Disease Unit, Royal Liverpool University Hospital (member of Liverpool Health Partners), Liverpool, United Kingdom
Fang Wang
Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China
Peng Wu
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
Qi Qiu
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Jianli Yang
Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China
Kai Wang
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Peng Cui
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Yibing Cheng
Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China
Tianchen Zhang
Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China
Chun Guo
School of Public Health, Huazhong University of Science and Technology, Wuhan, China
Mengyao Zeng
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China; NHC key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Medical School, Fudan University, Shanghai, China
Lu Long
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Malik Peiris
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
Hongjie Yu
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China; Corresponding authors.
Background: Examining associations between viral genomic loads of enteroviruses and clinical severity is important for promoting and improving development of antiviral drugs related to hand, foot and mouth disease (HFMD). Methods: Throat swabs were collected from HFMD cases at acute phase of illness using a standardized technique in a prospective study. The viral genomic load was categorized into low, medium, and high groups using parameters of real-time reverse transcription-polymerase chain reaction. The clinical severities were assessed with four indicators, respectively. Findings: We analysed 1109 HFMD cases, including 538 children with CV-A6, 231 with CV-A16, 156 with EV-A71, 78 with CV-A10, 59 with CV-A4, and 47 with CV-A2. EV-A71 genomic load categories were associated with risks of diagnoses of CNS complications (p = 0.016), requiring systemic corticosteroids or IVIG (p = 0.011), intensive care unit admission (p = 0.002) and length of hospital stay over 5 days (p = 0.048). In the multivariate analyses, point estimates of adjusted odds ratio (OR) tended to increase with viral genomic loads for all four severe outcomes and ORs of highest viral genomic load were all significantly larger than one for EV-A71. Interpretation: HFMD clinical severities positively associate with viral genomic loads of EV-A71 in throat swabs. Specific antiviral drugs should be developed to reduce enterovirus load and to alleviate the clinical severities for HFMD cases. Funding: National Science Fund for Distinguished Young Scholars
