Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study

Abstract

Background and objectives: The relationship between COVID-19 and epilepsy is uncertain. We studied the potential association between COVID-19 and seizures or epilepsy in the 6 months after infection.

Methods: We applied validated methods to an electronic health records network (TriNetX Analytics) of 81 million people. We closely matched people with COVID-19 infections to those with influenza. In each cohort, we measured the incidence and hazard ratios (HRs) of seizures and epilepsy. We stratified data by age and by whether the person was hospitalized during the acute infection. We then explored time-varying HRs to assess temporal patterns of seizure or epilepsy diagnoses.

Results: We analyzed 860,934 electronic health records. After matching, this yielded 2 cohorts each of 152,754 patients. COVID-19 was associated with an increased risk of seizures and epilepsy compared with influenza. The incidence of seizures within 6 months of COVID-19 was 0.81% (95% CI 0.75-0.88; HR compared with influenza 1.55 [1.39-1.74]). The incidence of epilepsy was 0.30% (0.26-0.34; HR compared with influenza 1.87 [1.54-2.28]). The HR of epilepsy after COVID-19 compared with influenza was greater in people who had not been hospitalized and in individuals younger than 16 years. The time of peak HR after infection differed by age and hospitalization status.

Discussion: The incidence of new seizures or epilepsy diagnoses in the 6 months after COVID-19 was low overall, but higher than in matched patients with influenza. This difference was more marked in people who were not hospitalized, highlighting the risk of epilepsy and seizures even in those with less severe infection. Children appear at particular risk of seizures and epilepsy after COVID-19 providing another motivation to prevent COVID-19 infection in pediatric populations. That 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.

Figure 1. Kaplan-Meier Curves Comparing the 6-Month Cumulative Incidence of the Primary Outcome Between Matched Cohorts of Patients With COVID-19 vs Influenza

An increased probability of being diagnosed with seizures or epilepsy is observed in the 6 months after COVID-19 compared with after influenza. The shaded areas around the curves represent 95% CI.

Figure 2. Kaplan-Meier Curves Comparing the 6-Month Cumulative Incidence of the Different Outcomes Between Matched Subgroups of Patients With COVID-19 vs Influenza

Compared with influenza, COVID-19 associates with an increased probability of being diagnosed with seizures and/or epilepsy in both age groups. The risk of epilepsy was more marked in individuals younger than 16 years. The shaded areas around the curves represent 95% CI.

Figure 3. Kaplan-Meier Curves Comparing the 6-Month Cumulative Incidence of the Primary Outcome Between Matched Subgroups of Nonhospitalized and Hospitalized Patients With COVID-19 vs Influenza

In people who were hospitalized the risks of seizures and/or epilepsy were similar after COVID-19 and influenza infections. In nonhospitalized patients, COVID-19 associated with significantly increased risks of seizures and/or epilepsy. The shaded areas around the curves represent 95% CI.

Figure 4. Time-Varying Hazard Ratios for the Primary Analysis (Left) and Nonhospitalized/Hospitalized and Pediatric/Adult Subgroups

The time of the peak HR is noted on the x-axis. The left-most panel in each row is identical to facilitate comparison. The peak HR in the whole cohort is at 23 days, similar to that seen in those older than 16 years. In those younger than 16 years, the peak is delayed to 50 days and, at that point, the HR is nearly 3.0. Hospitalized patients show a peak HR at 9 days, while in nonhospitalized patients, the peak HR is at 41 days.