Clinical presentation and outcomes of SARS-CoV-2 related encephalitis: the ENCOVID multicentre study

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

BACKGROUND: Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes. METHODS: The ENCOVID multicentre study included patients with encephalitis with full infectious screening, CSF, EEG, MRI data and confirmed SARS-CoV-2 infection recruited from 13 centres 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 RT-PCR resulted negative. Based on MRI, cases were classified as 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 (p=0.001) 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 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.