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

Objective: Coronavirus disease-19 (COVID- 19), caused by SARS-CoV- 2, hasled to a global pandemic since December 2019. People with epilepsy (PwE) facehigher 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 re-cords of PwE with confirmed SARS-CoV-2 infection (COVID+) from four Italianhospitals (March 2020–December 2021). A control group (COVID−) includedage- and sex-matched PwE without infection. Demographics, epilepsy features,COVID-19 severity, and neurological/psychiatric outcomes were assessed atbaseline and at 6 and 12 months. Statistical analyses included regression and lin-ear mixed model (LMM).Results: Among 130 patients (38 COVID+, 92 COVID−), no baseline differ-ences 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 neuro-logical disorders persisted (p < 0.01), with more treated neurological symptoms(p < 0.01). LMM analysis found no significant seizure frequency differencesover 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 psychiatriceffects in PwE. While acute seizure frequency changes are transient, cognitiveimpairment, insomnia, and depression persist, underscoring the need for con-tinuous monitoring and personalized care.Plain Language Summary: This study investigated long-term neurological andpsychiatric 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 in-creased seizure frequency and more psychiatric and neurological symptoms,often requiring treatment. At 12 months, seizure frequency stabilized, but cog-nitive issues, depression, and insomnia persisted. These findings highlight thatwhile seizure changes may be temporary, COVID-19 has lasting neuropsychiatriceffects in PwE, emphasizing the importance of long-term monitoring and indi-vidualized therapeutic strategies.