COVID-19 patients—especially children and those with nonsevere infections—are 55% more likely to develop epilepsy or seizures in the next 6 months than those who have influenza, but the overall risk remains very low, concludes a study published yesterday in Neurology.
A team led by University of Oxford researchers analyzed electronic health record data from 152,754 COVID-19 patients and an equal number of matched flu patients from Jan 20, 2020, to May 31, 2021. Most were patients at US healthcare systems, and none had a history of epilepsy or seizures.
Risks more marked in children
The rate of new-onset epilepsy or seizures was 0.94% among COVID-19 patients, compared with 0.60% in those who had flu. The incidence of seizures in the 6 months after COVID-19 infection was 0.81% (95% confidence interval [CI], 0.75 to 0.88; hazard ratio [HR] compared with flu, 1.55).
The incidence of epilepsy was 0.30% (95% CI, 0.26 to 0.34; HR relative to flu, 1.87). The risk of epilepsy after COVID-19 compared with flu was higher in nonhospitalized patients and in those younger than 16 years.
Relative to flu, COVID-19 increased the rate of the composite endpoint of seizures or epilepsy in both children (1.34% vs 0.69%; HR, 1.85) and adults (0.84% vs 0.54%; HR, 1.56). While the contrast between COVID-19 and flu appears more distinct among children, moderation of this endpoint by age was nonsignificant (moderation coefficient, 0.20).
The risk was significantly greater for both seizures and epilepsy measured separately in both age-groups. The risk of epilepsy after COVID-19 versus flu was significantly moderated by age and more evident among children than adults (moderation coefficient, 0.68).
Compared with flu, the risk of seizures or epilepsy after COVID-19 in nonhospitalized patients was significantly higher (0.72% vs 0.48%; HR, 1.44) but not in hospitalized patients (2.90% vs 2.40%; HR, 1.14). But hospitalization status was not a significant moderator (moderation coefficient, 0.12).
Likewise, the risk in both seizures and epilepsy measured separately was significantly increased only in the nonhospitalized group. Hospitalization status was a significant moderator for the link between COVID-19 and epilepsy (with the association more distinct among nonhospitalized patients; moderation coefficient, 0.52) but not for seizures (moderation coefficient, 0.047).
For all patients, the peak risk of seizures or epilepsy between COVID-19 and influenza was 23 days after infection. The risk was highest at 21 days in adults and 50 days in children. At 50 days, children were nearly three times more likely to have seizures or epilepsy after COVID-19 than after flu.
Among patients hospitalized for COVID-19 or flu, the risk of seizures or epilepsy peaked at 9 days, compared with 41 days in the nonhospitalized. At that point, nonhospitalized patients were more than twice as likely to have seizures or epilepsy after COVID-19 than flu.
Yet COVID-related seizures are rare, with an incidence of under 1%, lower than that of severe acute respiratory syndrome (SARS; 2.7%) and Middle East respiratory syndrome (MERS; 8.6%).
Role of monitoring
The researchers said that the findings in outpatients underscore the risk of epilepsy and seizures even those with mild or moderate COVID-19. Likewise, "children appear at particular risk of seizures and epilepsy after COVID-19 providing another motivation to prevent COVID-19 infection in pediatric populations," they wrote. "The varying time of peak risk related to hospitalization and age may provide clues as to the underlying mechanisms of COVID-associated seizures and epilepsy."
COVID-19, the authors said, may impair neurologic function by affecting the brains cells that make up the lining of blood vessels or by causing inflammation, immune overreaction, or other mechanisms. They added that the study was limited by the inability to identify which virus variants caused the infections.
The long-term outcomes of patients diagnosed with post-COVID seizures remains poorly understood, the researchers said. "It will be important to monitor these individuals to determine if further seizures supervene," they wrote. "In those who do start medication, especially children, it will be crucial to track seizure profiles and long term neurodevelopmental/neurocognitive outcomes."
Senior author Arjune Sen, MD, PhD, said in an American Academy of Neurology press release that the findings have important clinical implications. "People should interpret these results cautiously since the overall risk is low," he said.
"We do, however, recommend that health care professionals pay particular attention to individuals who may have more subtle features of seizures, such as focal aware seizures, where people are alert and aware of what is going on, especially in the three months following a less severe COVID-19 infection."
