Seizures as a main manifestation of severe pediatric SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, usually causes symptomatic illness in adults rather than children. In rare cases, mild COVID-19 symptoms occur in children, such as headache, drowsiness, muscle aches, fatigue, fever, and trivial respiratory symptoms.

In adults with severe SARS-CoV-2 infection, neurological signs such as stroke, transient ischemic attack, change in mental status and seizures occur. However, there is no evidence of neurological symptoms in children infected with the COVID-19 disease.

Possible link between seizures and severe COVID-19

A seizure has not been included as one of the neurological symptoms of COVID-19, as they occur in patients with severe SARS-CoV-2 infection during hospitalization. A UK study reported seizures in 5.5% of children admitted to the emergency department without a history of status epilepticus (SE). Similar to this report, a US study reported that 5.4% of children experience seizures when hospitalized due to COVID-19 with multisystem inflammatory syndrome. However, none of these studies take into account the severity of the COVID-19 disease at the time of the attacks in children.

A new study aimed to examine the clinical, demographic, laboratory, neurophysiological and imaging characteristics of children admitted to the emergency department (ED) with seizures and acute SARS-CoV-2 infection. This study is available in Seizure: European Journal of Epilepsy.

In this study, the authors examined whether seizure is an important symptom in children suffering from severe COVID-19 infection. They conducted a systematic retrospective study to identify children with COVID-19 infection (confirmed via RT-PCR test) and had to be admitted to the emergency room of a tertiary academic medical center between March 1 and December 31, 2020. The clinical and demographic data were obtained from the electronic health records and analysed.

The main findings

In this study, researchers identified a total of 175 children diagnosed with severe SARS-CoV-2 infection who were admitted to the emergency room during the study period. Of the 175 children, 11 showed seizures. Of these 11 candidates, 54% had a fever (>38°C).

The authors claim that this is the first-ever report on the clinical and demographic characteristics of a cohort of children experiencing seizures due to severe SARS-CoV-2 infection. This study suggests that seizures may be the primary manifestation of COVID-19 in children, especially, but not unequivocally, in children with a history of neurological disorders such as epilepsy. Researchers stated that further research is needed to determine the long-term prognosis. In the case of the pathogenesis of seizures during a coronavirus infection, scientists believe that it may not be directly related to the invasion of the virus into the brain.

This study further reported that out of five children with SE and those who experienced seizures, they tended to be older than those who had other symptoms. This conclusion was drawn by estimating the mean age of the subjects with epileptic seizures (11.5 years) and other complaints (7.9 years). Four out of five patients with SE belonged to age groups between 5-17 years. Of these five children, one child aged 2.9 suffered from fever and severe respiratory disease. This child was treated with multiple medications and ventilator support. Therefore, this study pointed to the possibility that, unlike other viral diseases, which tend to trigger seizures in infants and toddlers, SARS-CoV-2 infection triggers seizures in older children. However, a larger cohort is needed to validate this observation.

A previous study reported neurological manifestations of COVID-19 in adults, and six of the subjects studied had seizures, but none had SE. Researchers reported that, unlike in adults, seizures occur early in children with COVID-19 infection. Therefore, they believe that seizures could be an important manifestation of acute COVID-19 in children.

Five of the children with status epilepticus (SE) were treated with an appropriate dose of midazolam, an antiepileptic drug. All five responded positively to the treatment.

Conclusion

A previous study on animal models explained that seizures can be triggered by neuronal hyperexcitability through conformational changes. In addition, fever and glutamate release by cytokines (e.g. IL-1b) produced by the immune system can also trigger seizures. The current study also revealed the presence of elevated blood markers of inflammation in all children with COVID-19.

The current study also performed brain imaging (normal brain CT and magnetic resonance imaging) of the studied candidates. However, the reports from these tests do not contain relevant information about seizures related to COVID-19 in children. Furthermore, not much information was obtained from EEG patterns in acute COVID-19. Of the four patients subjected to EEG, only one showed intense bifrontal activity. Therefore, no specific EEG patterns associated with SARS-CoV-2 infection were identified.

In summary, the authors of this study indicated that children with a history of neurological disorders, especially epilepsy, have a high probability of having seizures when infected with a severe COVID-19 infection.

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