Assessing the Impact of the COVID-19 Pandemic on Childhood Arterial Ischemic Stroke: An Unanticipated Natural Experiment.

Background: The VIPS (Vascular Effects of Infection in Pediatric Stroke) II prospective cohort study aimed to better understand published findings that common acute infections, particularly respiratory viruses, can trigger childhood arterial ischemic stroke (AIS). The COVID-19 pandemic developed midway through enrollment, creating an opportunity to assess its impact.

Methods: Twenty-two sites (North America, Australia) prospectively enrolled 205 children (aged 28 days to 18 years) with AIS from December 2016 to January 2022, including 100 cases during the COVID-19 pandemic epoch, defined here as January 2020 to January 2022. To assess background rates of subclinical infection, we enrolled 100 stroke-free well children, including 39 during the pandemic. We measured serum SARS-CoV-2 nucleocapsid total antibodies (present after infection, not vaccination; half-life of 3-6 months). We assessed clinical infection via parental interview.

Results: The monthly rate of eligible AIS cases declined from spring through fall 2020, recovering in early 2021 and peaking in the spring. The prepandemic and pandemic cases were similar except pandemic cases had fewer clinical infections in the prior month (17% versus 30%; =0.02) and more focal cerebral arteriopathy (20% versus 11%; =0.09). Among pandemic cases, 26 of 100 (26%) had positive antibodies, versus 4 of 39 (10%) of pandemic-era well children (=0.04). The first SARS-CoV-2 positive case occurred in July 2020. Ten of the 26 (38%) positive cases had a recent infection by parental report, and 7 of those 10 had received a diagnosis of COVID-19. Only 1 had multisystem inflammatory syndrome in children. Median (interquartile range) nucleocapsid IgG total levels were 50.1 S/CO (specimen to calibrator absorbance ratio; 26.9-95.3) in the positive cases and 18.8 (12.0-101) in the positive well children (=0.33).

Conclusions: The COVID-19 pandemic may have had dual effects on childhood AIS: an indirect protective effect related to public health measures reducing infectious exposure in general, and a deleterious effect as COVID-19 emerged as another respiratory virus that can trigger childhood AIS.