Clinical Presentation and Outcomes of Severe Acute Respiratory Syndrome Coronavirus 2–Related Encephalitis: The ENCOVID Multicenter Study
Authors: Pilotto Andrea , Masciocchi Stefano , Volonghi Irene , Crabbio Massimo , Magni Eugenio , De Giuli Valeria , Caprioli Francesca , Rifino Nicola , Sessa Maria , Gennuso Michele , Cotelli Maria Sofia , Turla Marinella , Balducci Ubaldo , Mariotto Sara , Ferrari Sergio , Ciccone Alfonso , Fiacco Fabrizio , Imarisio Alberto , Risi Barbara , Benussi Alberto , Premi Enrico , Focà Emanuele , Caccuri Francesca , Leonardi Matilde , Gasparotti Roberto , Castelli Francesco , Zanusso Gianluigi , Pezzini Alessandro , Padovani Alessandro ,   SARS-CoV-2 related encephalopaties (ENCOVID) Study Group, Pilotto Andrea , Masciocchi Stefano , Volonghi Irene , Crabbio Massimo , del Zotto Elisabetta , Magni Eugenio , De Giuli Valeria , Caprioli Francesca , Rifino Nicola , Sessa Maria , Gennuso Michele , Cotelli Maria Sofia , Turla Marinella , Balducci Ubaldo , Mariotto Sara , Ferrari Sergio , Ciccone Alfonso , Fiacco Fabrizio , Guindani Massimiliano , Imarisio Alberto , Risi Barbara , Benussi Alberto , Poli Loris , Gipponi Stefano , Filosto Massimiliano , Premi Enrico , Gamba Massimo , Caratozzolo Salvatore , Cristillo Viviana , Libri Ilenia , Cola Francesca Schiano di , Piccinelli Stefano Cotti , Cortinovis Matteo , Scalvini Andrea , Baldelli Enrico , Locatelli Martina , Benini Matteo , Gazzina Stefano , Chiari Erika , Odolini Silvia , Focà Emanuele , Caccuri Francesca , Caruso Arnaldo , Leonardi Matilde , Ambrosi Claudia , Pinelli Lorenzo , Gasparotti Roberto , Gerevini Simonetta , Ciceri Elisa Francesca Maria , Castelli Francesco , Zanusso Gianluigi , Ferraro Bruno , Volta Giorgio Dalla , Pezzini Alessandro , Padovani Alessandro 
Published: September 2020

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; 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.