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

• DOI: 10.1093/infdis/jiaa609
• Publication Date: 2020-09-26T19:10:16Z
• Authors: Andrea Pilotto; Stefano Masciocchi; Irene Volonghi; Massimo Crabbio; Eugenio Magni; Valeria De Giuli; Francesca Caprioli; Nicola Rifino; Maria Sessa; Michele Gennuso; Maria Sofia Cotelli; Marinella Turla; Ubaldo Balducci; Sara Mariotto; Sergio Ferrari; Alfonso Ciccone; Fabrizio Fiacco; Alberto Imarisio; Barbara Risi; Alberto Benussi; Enrico Premi; Emanuele Focà; Francesca Caccuri; Matilde Leonardi; Roberto Gasparotti; Francesco Castelli; Gianluigi Zanusso; Alessandro Pezzini; Alessandro Padovani; ; Andrea Pilotto; Stefano Masciocchi; Irene Volonghi; Massimo Crabbio; Elisabetta del Zotto; Eugenio Magni; Valeria De Giuli; Francesca Caprioli; Nicola Rifino; Maria Sessa; Michele Gennuso; Maria Sofia Cotelli; Marinella Turla; Ubaldo Balducci; Sara Mariotto; Sergio Ferrari; Alfonso Ciccone; Fabrizio Fiacco; Massimiliano Guin...; Alberto Imarisio; Barbara Risi; Alberto Benussi; Loris Poli; Stefano Gipponi; Massimiliano Filosto; Enrico Premi; Massimo Gamba; Salvatore Caratoz...; Viviana Cristillo; Ilenia Libri; Francesca Schiano...; Stefano Cotti Pic...; Matteo Cortinovis; Andrea Scalvini; Enrico Baldelli; Martina Locatelli; Matteo Benini; Stefano Gazzina; Erika Chiari; Silvia Odolini; Emanuele Focà; Francesca Caccuri; Arnaldo Caruso; Matilde Leonardi; Claudia Ambrosi; Lorenzo Pinelli; Roberto Gasparotti; Simonetta Gerevini; Elisa Francesca M...; Francesco Castelli; Gianluigi Zanusso; Bruno Ferraro; Giorgio Dalla Volta; Alessandro Pezzini; Alessandro Padovani
• Keywords: Aged, 80 and over; Male; ADEM; SARS-CoV-2; encephalitis; COVID-19; Electroencephalography; Middle Aged; Magnetic Resonance Imaging; neuroinflammation; 3. Good health; 03 medical and health sciences; Infectious Diseases; 0302 clinical medicine; Italy; Immunology and Allergy; Encephalitis; Humans; Female; Longitudinal Studies; Aged

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.