ABSTRACT
BACKGROUND: Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of encephalitis in coronavirus disease 2019 (COVID-19) disease, but very few data have focused on clinical presentations, clinical course, response to treatment, and outcomes. METHODS: The SARS-CoV-2 related encephalopaties (ENCOVID) multicenter study included patients with encephalitis with full infectious screening, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) data and confirmed SARS-CoV-2 infection recruited from 13 centers in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment, and outcomes were recorded. RESULTS: Twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction resulted negative. Based on MRI, cases were classified as acute demyelinating encephalomyelitis (ADEM; nâ =â 3), limbic encephalitis (LE; nâ =â 2), encephalitis with normal imaging (nâ =â 13), and encephalitis with MRI alterations (nâ =â 7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (Pâ =â .001) and were associated with previous, more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to those with other encephalitis. CONCLUSIONS: SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes.