Clinical Presentation and Outcomes of Severe Acute Respiratory Syndrome Coronavirus 2-Related Encephalitis: The ENCOVID Multicenter Study

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; n=3), limbic encephalitis (LE; n=2), encephalitis with normal imaging (n=13), and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (P=.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.