Clinical characteristics and severity of hand, foot, and mouth disease by virus serotype: A prospective hospital-based cohort study

Abstract

The circulating enteroviruses (EVs) serotypes in hand, foot and mouth disease (HFMD) inpatients remained unclear. This study aimed to investigate the serotype-specific associations between clinical characteristics and severity of HFMD inpatients. The study utilised a prospective, hospital-based cohort design and a tiered diagnostic algorithm incorporating real-time RT-PCR and nested RT-PCR for sero-typing. Clinical data were prospectively collected throughout hospitalization. Clinical severity was measured using diagnoses of central nervous system (CNS) complications and three other outcomes. A total of 1768 inpatients were enrolled consecutively between February 2017 and February 2018. The proportions of CNS complications varied by serotype (p < 0.001), with the highest for EV-A71 (40%), followed by CV-A4 (17%), CV-A2 (13%), CV-A10 (10%), CV-A6 (7%), and CV-A16 (4%). Children with CV-A2 and CV-A4 were less likely to have rashes on hands, feet, or buttocks and more likely to develop high fever, while those with EV-A71 had fewer mouth lesions. Of 230 lab-confirmed HFMD inpatients with CNS complications, EV-A71 accounted for 45% while CV-A6, CV-A16, CV-A4, CV-A10 and CV-A2 accounted for 35%. The logistic regression analysis revealed that non-CNS-specific symptoms such as cold limbs and vomiting, and clinical testing indicators including blood globulin, platelet, serum chloride and neutrophil counts, were associated with CNS complications. Non-EV-A71 EVs can also cause severe diseases, but those with EV-A71 infection are more likely to suffer CNS complications and other severe manifestations. The study highlighted the emergence of enterovirus serotypes, suggesting the need for future research on virus changes and associated disease burden.