Pediatric varicella zoster virus associated arterial ischemic stroke - A post-pandemic rise in incidence in Denmark

BACKGROUND: Varicella Zoster Virus (VZV) associated Acute Ischemic Stroke (AIS) in pediatric populations is a rare and potentially underrecognized condition. The global COVID-19 pandemic has led to significant changes in infectious disease patterns, including possible impacts on the incidence of VZV infections. This study describes the incidence of VZV associated AIS in Denmark from 2013 to 2023 using national surveillance data from Denmark. Furthermore, the study investigates a cluster of VZV-associated AIS cases identified over a 10-month period in 2022 in a geographically confined area north-west of Copenhagen, Denmark, following the lifting of COVID-19 restrictions.

METHODS: We analyzed national surveillance data on cerebral spinal fluid samples and VZV and AIS diagnoses in nationwide patient registries to estimate the incidence of VZV associated AIS pre, during and post- COVID era in Denmark. To evaluate the clinical disease severity and risk factors and outcome in the post-COVID era we conducted a retrospective case series analysis of four pediatric patients diagnosed with VZV-associated AIS from Greater Copenhagen.

RESULTS: Our analysis revealed a notable clustering of VZV-associated AIS cases nationwide, suggesting an increased incidence in Denmark after COVID-19 restrictions were lifted. Clinical presentations of our cases were comparable with the pre-COVID era and did not suggest a more virulent VZV subtype.

CONCLUSION: The observed cluster of pediatric VZV-associated AIS cases post-COVID-19 restrictions and national survey data showed a rise in incidence which could reflect an increase in VZV disease due to diminished herd immunity post-COVID 19. The clinical presentations of VZV associated AIS were in keeping with previous reports and the clinical presentations were both unspecific and transient in character.