Exploring the long-term effects of COVID-19 in patients with epilepsy: A multicenter Italian observational study

Abstract

Objective: Coronavirus disease-19 (COVID-19), caused by SARS-CoV-2, has led to a global pandemic since December 2019. People with epilepsy (PwE) face higher risks of severe COVID-19 outcomes and may be more vulnerable to long-term neurological and psychiatric effects. Methods: This multicenter, retrospective cohort study reviewed medical records of PwE with confirmed SARS-CoV-2 infection (COVID+) from four Italian hospitals (March 2020–December 2021). A control group (COVID−) included age- and sex-matched PwE without infection. Demographics, epilepsy features, COVID-19 severity, and neurological/psychiatric outcomes were assessed at baseline and at 6 and 12 months. Statistical analyses included regression and linear mixed model (LMM). Results: Among 130 patients (38 COVID+, 92 COVID−), no baseline differences were found in demographics, epilepsy characteristics, or comorbidities. At 6 months, the COVID+ group showed increased seizure frequency (p = 0.03) and higher rates of psychiatric (p < 0.01) and neurological symptoms (p < 0.01), requiring specific treatment (p = 0.01). At 12 months, psychiatric and neurological disorders persisted (p < 0.01), with more treated neurological symptoms (p < 0.01). LMM analysis found no significant seizure frequency differences over time (p = 0.47), but focal-to-bilateral tonic–clonic seizures showed a time-dependent interaction (p = 0.025). Significance: SARS-CoV-2 infection has lasting neurological and psychiatric effects in PwE. While acute seizure frequency changes are transient, cognitive impairment, insomnia, and depression persist, underscoring the need for continuous monitoring and personalized care. Plain Language Summary: This study investigated long-term neurological and psychiatric outcomes in people with epilepsy (PwE) after COVID-19 infection. We compared 38 PwE with confirmed SARS-CoV-2 infection to 92 uninfected controls, matched by age and sex. At 6 months, infected patients showed increased seizure frequency and more psychiatric and neurological symptoms, often requiring treatment. At 12 months, seizure frequency stabilized, but cognitive issues, depression, and insomnia persisted. These findings highlight that while seizure changes may be temporary, COVID-19 has lasting neuropsychiatric effects in PwE, emphasizing the importance of long-term monitoring and individualized therapeutic strategies.