Israel Study Warns That Seizures Are A Main Manifestation Of Severe SARS-CoV-2 infection In Children

Pediatric COVID-19: Researchers from the Pediatric Neurology Unit at the Hadassah Medical Center-Israel and the School of Medicine at the Hebrew university of Jerusalem-Israel have in a clinical study found that seizures are a manifestation of severe SARS-CoV-2 infection in children.

 
The study team conducted a systematic retrospective study to identify all children who presented to the emergency departments of a tertiary academic medical center between March 1st and December 31st 2020 and had a SARS-CoV-2 infection based on RT-PCR (reverse transcription-polymerase chain reaction) from nasopharyngeal swab. Clinical and demographic data were extracted from the electronic medical records and reviewed.
 
In all a total of 175 children were diagnosed with acute SARS-CoV-2 infection in the emergency departments during the study period. Of those, 11 presented with seizures. Age ranged from six months to 17 years and 4 were girls. Five presented with status epilepticus and responded to loading doses of anti-seizure medications. Six had fever. Seven had prior history of neurological disorder.
 
Alarmingly the study found that unlike in adults, seizures occur early and may be the main manifestation of acute COVID-19 in children. Seizures, including status epilepticus, may occur without fever even in children with no history of epilepsy and are not associated with severe disease. A high index of suspicion is required for early diagnosis thus infection control measures can be taken.
 
The study findings were published in the peer reviewed journal: Seizure (The European Journal of Epilepsy) https://www.seizure-journal.com/article/S1059-1311(21)00295-8/fulltext
 
The SARS-CoV-2 coronavirus, the causal agent of the COVID-19 pandemic, mostly causes symptomatic disease in adults rather than in children. In rare cases, mild COVID-19 symptoms such as headache, drowsiness, myalgia, fatigue, fever, and trivial respiratory symptoms appear in children.
 
It has been found that in adults with severe SARS-CoV-2 infection, neurological manifestations such as stroke, transient ischemic attack, alteration in mental status, and seizures occur. However, no evidence of neurological symptoms in children infected with COVID-19 disease is available.
 
To date, a seizure has not been included as one of the COVID-19 neurological symptoms as they occur in patients with severe SARS-CoV-2 infection during hospital admission.
 
A clinical research conducted in the UK reported seizures in 5.5% of children admitted to the emergency department without having a history of status epilepticus (SE). https://pubmed.ncbi.nlm.nih.gov/32960186/
 
Interestingly similar to this report, an American study reported that 5.4% of children suffer seizures when admitted to the hospital due to COVID-19 with the multisystem inflammatory syndrome. https://pubmed.ncbi.nlm.nih.gov/33666649/
 
It should be noted however that none of these studies consider the severity of the COVID-19 disease at the time of the seizures in children.
 
The style="font-size:16px">Pediatric COVID-19 study aimed to investigate the clinical, demographic, laboratory, neurophysiological, and imaging characteristics of children admitted to the emergency department (ED) with seizures and acute SARS-CoV-2 infection.
 
The study team investigated if a 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 required admission to the ED of a tertiary academic medical center between 1st March and 31st December 2020. The clinical and demographic data were obtained from the electronic medical records and analyzed.
 
The study team identified a total of 175 children who were diagnosed with severe SARS-CoV-2 infection and were admitted to the ED during the study period. Out of the 175 children, 11 presented seizures. Out of these 11 candidates, 54% had a fever (>38°C).
 
The study team claims that this is the first-ever report on the clinical and demographic characteristics of a cohort of children undergoing seizures due to severe SARS-CoV-2 infection.
 
Importantly this study suggests that seizures could be the primary manifestation of COVID-19 in children, especially, but not unequivocally, in children with a history of neurological disorders like epilepsy.
 
The study team states that further research is required to determine the long-term prognosis. In the case of the pathogenesis of seizures during coronavirus infection, scientists believe that it might not be directly linked with the invasion of the virus in the brain.
 
The study findings further reported that among the five children with SE and those who underwent seizures tended to be older than those who presented other complaints.
 
This study conclusion was drawn by estimating the mean age of the subjects with seizures (11.5 years) and other complaints (7.9 years). Four of the five patients with SE belonged to age groups between 5-17 years of age. Among these five children, one child who was 2.9-years-old suffered from fever and severe respiratory disease. This child was treated with multiple medications and ventilator support.
 
Hence, this research indicated the possibility that, unlike other viral illnesses, which tend to cause seizures in infants and toddlers, SARS-CoV-2 infection causes seizures in older children. However, a larger cohort is required to validate this observation.
 
A past clinical study reported neurological manifestations of COVID-19 in adults, and six of the studied subjects had seizures, but none had SE. https://n.neurology.org/content/author-response-prospective-study-neurologic-disorders-hospitalized-covid-19-patients-new-1
 
The study team reported that, unlike in adults, seizures occur early in children with COVID-19 infection. Therefore, they believe seizures could be an important manifestation of acute COVID-19 in children.
 
The study team further reported that five of the children who presented with status epilepticus (SE) were treated with an appropriate dose of midazolam, an anti-seizure medication. All five responded positively to the treatment.
 
Another past study on animal models explained that seizures could be caused by neuronal hyperexcitability by conformational changes. Additionally, fever and glutamate release by cytokines (e.g., IL-1b) produced by the immune system could also cause seizures. https://journals.sagepub.com/doi/full/10.1177/2633105520956973
 
Interestingly study findings from this current research also revealed the presence of enhanced blood markers of inflammation in all children with COVID-19.
 
The study team also conducted brain imaging (normal brain CT and magnetic resonance imaging) of the studied candidates. However, the reports of these tests did not portray any relevant information regarding seizures associated with COVID-19 in children.
 
Also not much information was obtained from EEG patterns in acute COVID-19. Among the four patients who were subjected to EEG, only one showed intense bi-frontal activity. Hence, no specific EEG patterns were identified associated with SARS-CoV-2 infection.
 
The study team concluded that children with a history of neurological disorders, especially epilepsy, have a high probability of undergoing seizures when infected with severe COVID-19 infection.
 
The main limitations of the study are the relatively small number of children with seizures and the retrospective nature of it. Laboratory tests, imaging and EEG were performed based on clinical decisions and thus data is available for only some of the children.
 
The study team further commented, “The COVID-19 pandemic continues to affect thousands of patients daily worldwide, including children. The emergence of new mutations of the virus may increase the rate of symptoms in children and it is possible that despite vaccination, SARS-CoV-2 will continue to infect people worldwide. Early diagnosis of COVID-19 is important for infection control. Children who present with symptoms other than influenza-like, might not be tested and thus spread the virus. Moreover, the long-term outcome of children with acute symptomatic seizures associated with COVID-19 is still unknown. We therefore suggest a high index of suspicion of acute COVID-19 infection in children who present with new onset seizures or exacerbation of prior epilepsy, with or without fever, regardless of other typical signs of acute COVID-19.”
 
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