Neonatal hand, foot, and mouth disease due to coxsackievirus A6 in Shanghai.

BACKGROUND: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. METHODS: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1ß, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings. RESULTS: There were 16 neonates among the 12,608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about 1 week after onset. None of the neonates had sequelae. CONCLUSIONS: In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

Genomic surveillance of coxsackievirus A10 reveals genetic features and recent appearance of genogroup D in Shanghai, China, 2016-2020.

Coxsackievirus A10 (CVA10) is one of the major causative agents of hand, foot and mouth disease (HFMD). To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai, China, we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020. In the past five years, CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%. The annual distribution experienced significant fluctuations over the past five years. In addition to entire VP1 sequencing, complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed. A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis. The CVA10 sequences in this study mainly belonged to genogroup C and presented 91%-100% nucleotide identity with other Chinese isolates based on VP1 region. For the first time, our study reported the appearance of CVA10 genogroup D in Chinese mainland, which had led to large-scale outbreaks in Europe previously. The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt, which suggesting intertypic recombination with CVA16 genogroup D. To conclusion, CVA10 genogroup C was the predominant genogroup in Shanghai during 2016-2020. CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland. Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.