This study showed that although the number of children with FS in the COVID-19 group was lower than that in the non-COVID-19 group, all conditions were equal, this does not mean that COVID-19 infection reduces the risk of FS. Rather, it may reflect a significant increase in the overall incidence of FS caused by COVID-19 infection. This was consistent with the results of multiple studies(14, 15). A South African study found that 20% of 139 children under the age of 13 admitted to hospital with COVID-19 had seizures(16). A study in Sweden also found that four children with COVID-19 experienced seizures in just one week(17). The main mechanism by which COVID-19 causes a series of nervous system symptoms is that it invades host cells by binding to angiotensin-converting enzyme 2 and is expressed on the surface of various nerve cells(18), leading to seizures, headache, paralysis, and other symptoms(19). However, the severity of neurological sequelae of COVID-19 may need to be studied long enough to be explored in depth. By identifying differences in the clinical features of seizures in children caused by COVID-19, it may be crucial to elucidate the pathophysiology and potential possibilities of COVID-19 damage to the CNS in the future.
Consistent with the Swedish study, boys were more likely to have seizures regardless of COVID-19 infection(17). However, the sample size was too small to assert a gender preference in the occurrence of COVID-19 seizures, and the results of this study may help to test this idea.
This study found that age was an independent protective factor for FS in COVID-19, consistent with previous studies(20, 21). Younger children have immature brain development, higher neuronal excitability, lower blood-brain barrier integrity, and lower tolerance to external stimulation. They are more susceptible to nervous system damage caused by viral infection and increase the risk of seizures.
This study found that blood urea nitrogen level was an independent protective factor for COVID-19 FS. Urea nitrogen is the end product of protein metabolism in the body, and its level reflects the state of protein metabolism in the body(22). Urea nitrogen can inhibit glutamate receptor activity, reduce neuronal excitability, and may affect the permeability of the blood-brain barrier, limiting the entry of neurotoxic substances into the central nervous system, thereby helping to maintain the homeostasis of the central nervous system and reducing the risk of convulsion(22). This is in order to investigate the pathophysiology of FS and further provide a new perspective.
The results of this study indicated that albumin was an independent risk factor for FS in COVID-19. As a harmful acute-phase protein, the increase of albumin usually reflects some degree of inflammation. Inflammatory mediators may act directly on the central nervous system, increasing seizure susceptibility (23).
This study showed that platelets were an independent protective factor for COVID-19 FS. Platelets are essential in neurotransmitter release and vasoconstriction processes, and their abnormalities may affect neuronal excitability(24). Platelets are also involved in regulating the inflammatory response, and their reduction may aggravate the central nervous system damage caused by COVID-19(25).
Electrolyte imbalances that may affect the neurotransmitter release and conduction cause neuronal excitability change, thus inducing seizure(26, 27). This study showed that decreased potassium and increased sodium ions in cerebrospinal fluid were independent risk factors for FS in COVID-19. Potassium imbalance can cause changes in neuronal membrane potential, enhance excitability, and induce seizures(28). Sodium imbalance can lead to cellular edema, cause neuronal dysfunction, and increase susceptibility to seizures(29, 30). Studies have shown that CSF electrolyte levels can more directly reflect the pathological changes of the central nervous system and are critical biological markers of FS(31). Therefore, cerebrospinal fluid electrolyte indicators may be superior to hematological indicators in predicting and explaining the occurrence of FS, which also provides an essential basis for the study of the pathogenesis of COVID-19 FS and formulation of prevention and treatment strategies.
Our study also has some limitations. First, we had limited data on the cerebrospinal fluid, which was obtained only when there was clinical suspicion of intracranial infection. Second, since this study was conducted after the COVID-19 prevention and control policy was opened in China during the Omicron period, the results may be inconsistent for other variants. Third, as it is a retrospective study, the data collected are limited and lack more specific descriptions, such as the duration of seizures. More detailed FS data reports can be added to explore the pathogenesis further, and perhaps more surprising findings can be obtained.