Clinical Presentation and Outcomes of Severe Acute Respiratory Syndrome Coronavirus 2–Related Encephalitis: The ENCOVID Multicenter Study
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, Sérgio 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, SARS-CoV-2 related encephalopaties (ENCOVID) Study Group, 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 Guindani, Alberto Imarisio, Barbara Risi, Alberto Benussi, Loris Poli, Stefano Gipponi, Massimiliano Filosto, Enrico Premi, Massimo Gamba, Salvatore Caratozzolo, Viviana Cristillo, Ilenia Libri, Francesca Schiano di Cola, Stefano Cotti Piccinelli, 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 Ciceri, Francesco Castelli, Gianluigi Zanusso, B Ferraro, Giorgio Dalla Volta, Alessandro Pezzini, Alessandro Padovani
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.