Study finds that pediatric stroke is associated with COVID-19 infections but not with multisystem inflammatory syndrome

In a recent study published in Pediatric Neurology, researchers investigated whether coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) were associated with an increased risk of ischemic stroke in pediatric populations.

Background

Growing evidence suggests that adult COVID-19 patients are at an increased risk of stroke, which is attributed to various factors such as hypercoagulability, immune-mediated thrombosis, changes in the renin-angiotensin system, cardioembolism, and other COVID-19 mediated changes to the cardiac and nervous systems.

The ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to use the angiotensin-converting enzyme-2 (ACE-2) receptors to enter host cells is also linked to neurotropism and the effect of the virus on multiple organ systems.

However, there is a scarcity of information on whether children with COVID-19 are at a higher risk of stroke. While studies have found no increase in the risk of ischemic stroke in pediatric COVID-19 patients during the early pandemic, neurological complications, and some forms of vasculopathy have been observed in a quarter of the MIS-C patients. Furthermore, while thromboembolism and stroke have been considered rare complications of MIS-C, the causal relationships are not well understood.

About the study

In the present study, the researchers conducted retrospective analyses on two population-based cohorts of children under 18. The first cohort included children diagnosed with intracranial hemorrhage, cerebral infarction, ischemic stroke, or cerebrovascular accident between March 2020 and June 2021. The second comprised children hospitalized with stroke between March 2015 and February 2020 at the Primary Children’s Hospital in Utah, United States.

Data on demographic characteristics such as gender, age, socioeconomic status, insurance coverage, and race or ethnicity were obtained from electronic records. Additional information such as medical histories, COVID-19 polymerase chain reaction (PCR) test results, COVID-19 vaccination data, hospital, and intensive care unit admission dates and duration, the time elapsed between COVID-19 symptom onset and stroke, National Institute of Health Stroke Scale (NIHSS) upon presentation of stroke, stroke characteristics, treatment administered, and stroke outcomes were evaluated.

Results

The results reported 16 cases of pediatric ischemic strokes in patients between the ages of eight months and 17 years. The incidence of ischemic stroke was correlated with an increase in COVID-19 infections in children but was not associated with an increased occurrence of MIS-C.

One-third of the patients who had a stroke had previous SARS-CoV-2 infections, had been diagnosed with MIS-C, were not vaccinated, or had antibodies against SARS-CoV-2 when they suffered the stroke. Since other viral infections during the time had decreased, COVID-19 is thought to be a trigger for stroke. Contrary to previous studies that reported increased focal cerebral arteriopathy associated with COVID-19, the present study found large-vessel occlusive stroke more prevalent in the pandemic and pre-pandemic cohorts.

While three of the patients had been diagnosed with MIS-C at the stroke time, three other patients with mild or asymptomatic previous SARS-CoV-2 infections and no diagnosed MIS-C patients also suffered strokes. Only a quarter of the pandemic cohort patients were administered tissue plasminogen activator or a thrombectomy since the diagnosis of stroke in most patients in the pandemic, and pre-pandemic cohorts were delayed.

Furthermore, acute SARS-CoV-2 infections were not found to be associated with stroke, suggesting that stroke could be associated with the hyperinflammatory state observed in COVID-19 patients in the two to six weeks after recovery. Additionally, the prothrombotic state and hypercoagulability that results from the activation of clotting cascades and endothelial damage due to the viral infection have also been implicated in the occurrence of strokes in pediatric patients.

The study suggested that stroke could occur a month after the COVID-19 infection, possibly due to the hypercoagulability and prothrombotic state resulting from the weeks following SARS-CoV-2 infections. Furthermore, since the incidence of stroke in the pediatric population is rare, and the presentations of stroke symptoms in children are vague, it is often misdiagnosed or diagnosed late, delaying intervention.

Conclusions

To summarize, the study investigated the association between stroke, COVID-19 infections, and multisystem inflammatory syndrome in children using a retrospective analysis on two cohorts of pediatric stroke patients, one spanning the COVID-19 pandemic and one pre-pandemic.

The results indicated that stroke is a delayed complication of previous SARS-CoV-2 infections but is not associated with acute infections or MIS-C. Furthermore, stroke is often diagnosed late in pediatric patients due to vague symptoms, delaying treatments and interventions.