Impact of SARS-CoV-2 Variants and Vaccination on Pediatric Febrile Seizures: A Retrospective Cohort Study

Objective This study aimed to investigate the associations between SARS-CoV-2 variants, neuroinflammatory markers, vaccination history, and demographic characteristics in relation to the occurrence of febrile seizures (FS) in pediatric patients at a single tertiary medical center. Methods Retrospective cohort data were collected from a pediatric tertiary care institution between April 2020 and January 2023, encompassing 339 patients with PCR-confirmed SARS-CoV-2 infections. The cohort was separated into FS (n=102) and control (n=237) groups. A multivariable logistic regression analysis was employed to evaluate the impact of viral variants (Delta and Omicron sublineages), inflammatory markers (IL-6, D-dimer, CRP), vaccination status (unvaccinated, partially vaccinated, fully vaccinated), and demographic variables, while controlling for potential confounders. Results The incidence of FS among infants under one year of age was found to be 41.2%, in contrast to 17.7% in older children (OR=3.2, 95% CI: 1.8–5.7; P <0.001). Elevated levels of IL-6 exceeding 10 pg/mL and D-dimer levels surpassing 0.5 mg/L were independently associated with increased FS severity (adjusted OR [aOR]=2.8 and 2.1, respectively), as well as a 3.1-fold increase in the risk of recurrence. Full vaccination was linked to a 68% reduction in FS risk (aOR=0.32, 95% CI: 0.18–0.55), particularly benefiting infants. Additionally, male infants exhibited a 1.8-fold increased vulnerability ( P =0.016). Omicron sublineages (BA.5/XBB), which accounted for 78.4% of FS cases, correlated with heightened biomarker levels. Conclusion The findings suggest that IL-6 and D-dimer serve as valuable indicators for assessing the risk of FS in children infected with SARS-CoV-2. The protective effect of vaccination on neural tissues, in addition to its role in reducing viral transmission, is evident, highlighting the increased susceptibility in male infants.