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

• Published in: The Journal of infectious diseases Vol. 223; no. 1; pp. 28 - 37
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 04.01.2021
• Subjects: Aged; Aged, 80 and over; Case reports; Cerebrospinal fluid; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - therapy; Demyelination; DNA-directed RNA polymerase; EEG; Electroencephalography; Encephalitis; Encephalitis - classification; Encephalitis - diagnosis; Encephalitis - virology; Encephalomyelitis; Female; Humans; Infections; Italy; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Nervous system; Patients; Pleocytosis; Polymerase chain reaction; Ribonucleic acid; RNA; Severe acute respiratory syndrome coronavirus 2; Italy; COVID-19; SARS-CoV-2; encephalitis; ADEM; neuroinflammation
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiaa609

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. In this prospective multicenter study including 25 cases of encephalitis in severe acute respiratory syndrome coronavirus 2 infection, the majority of patients presented clinical, imaging, and cerebrospinal fluid findings, arguing for a cytokine-mediated mechanism.