Epidemiology of Enteroviruses Among Hospitalized Patients in Israel (2016–2024): CNS Involvement, Subtype Variability, and Seasonality

Enteroviruses (EVs) cause a spectrum of illnesses ranging from mild to severe, including neurological complications. In this study, the molecular epidemiology, clinical impact, and seasonality of EVs were evaluated among hospitalized patients in a large tertiary medical center in Israel from 2016 to 2024. A total of 11,246 cerebrospinal fluid (CSF) samples and 5,744 stool samples were tested for EV RNA using RT-PCR, with 7.1% (n = 798) and 19.3% (n = 1,110) testing positive, respectively. Positive samples were sequenced for genotype identification based on partial VP1 sequences with 70% genotype identification. The most commonly detected subtypes in CSF samples were: E-18 (16.4%), E-5 (80/567, 14.1%), E-6 (67/567, 11.8%), E-30 (64/567, 11.3%), CVB5 (37/567, 6.5%), E-4 (29/567, 5.1%), and CVB2 (28/567, 4.9%). These subtypes were also detected in stool samples during similar time periods. Seasonal analyses showed the expected summer peaks with unexpected off-season outbreaks in 2016, 2017, and 2022-2024. Additionally, EV positivity rates declined significantly during the SARS-CoV-2 pandemic (p = 0.006) followed by a resurgence in 2022-2023. Phylogenic analysis revealed genomic shifts in CVB2, E-5, E-6, E-18, and E-30, whereas CVB5 and E-4 showed no significant variations. CVB2 infections were particularly associated with severe illness in infants, with 10.6% of all sequenced cases requiring ICU admission. These findings demonstrate dynamic changes in EV epidemiology in Israel, including shifts in seasonality, genotype variability, and the impact of SARS-CoV-2 on EV circulation, highlighting the importance of continued molecular surveillance for identifying emerging strains and better understand trends relevant to public health.