Kevin O’Connor, MD

Beslow LA, Agner SC, Santoro JD, Ram D, Wilson JL, Harrar D, Appavu B, Fraser SM, Rossor T, Torres MD, et al. International Prevalence and Mechanisms of SARS-CoV-2 in Childhood Arterial Ischemic Stroke During the COVID-19 Pandemic. Stroke. 2022.

Over the last two years, data have shown an increased risk of ischemic stroke in the setting of SARS-CoV-2 infection. Beslow et al. explored the relationship between SARS-CoV-2 and childhood (age 29 days to 18 years) ischemic stroke based on data from multiple sites across 21 countries.

The sites reported 373 acute ischemic strokes from June to December 2020 during the same time that they recorded 7,231 pediatric SARS-CoV-2 hospitalizations. Of 335 (89.8%) childhood ischemic strokes that underwent testing for SARS-CoV-2, 23 (6.9%) were positive for the virus, and clinical information was available for 22 cases. The overall risk of childhood ischemic stroke in children hospitalized for SARS-CoV-2 was low at 0.32% (95% binomial exact CI, 0.20%-0.48%), but this may include children in whom the infection was found incidentally.

Most of the 23 children (n=13, 56.5%) with ischemic strokes had asymptomatic infections. Seven children (30.4%) had symptomatic COVID-19, and two children (8.7%) had multisystem inflammatory syndrome in children (MIS-C). Onset of infectious symptoms occurred seven days (median) prior to stroke (range 1-30 days). SARS-CoV-2 was the principal risk factor in six children (26.1%; four were symptomatic and two had MIS-C), a contributory risk factor in 13 children (56.5%; three were symptomatic), and incidental in three children (13.1%; none were symptomatic). Ten children (43.5%) had ischemic strokes in more than one vascular territory. In all five children (21.7%) with large vessel occlusion, SARS-CoV-2 was considered either a principal (n=2) or contributory (n=3) risk factor.

The mechanism for ischemic stroke in the setting of SARS-CoV-2 likely involves inflammatory processes prompting thrombosis and endothelial dysfunction. In the six children in which SARS-CoV-2 was the principal risk factor, three (13%) had arteritis/vasculitis (one with MIS-C) and three (13%) had focal cerebral arteriopathy (one with MIS-C), while 5 of the 6 had positive inflammatory markers. Although testing for inflammatory markers was inconsistent among 22 of the 23 childhood strokes, most (n=17, 77.3%) had elevations in one inflammatory marker: C-reactive protein (13/20, 65%); ferritin (4/13, 30.8%); erythrocyte sedimentation rate (3/10, 30%), and procalcitonin (5/5, 100%).

Based on these data, which is similar to prior studies, the risk of ischemic stroke in childhood SARS-CoV-2 infection is relatively low. SARS-CoV-2 may provoke ischemic stroke via inflammatory processes, and it remains unclear whether immune-mediated therapies might have a role in treatment like antithrombotic agents. Pediatric vaccines were not approved during the study timeframe, but vaccination status and incidence of ischemic stroke may be a future avenue of study.