Central neuroinflammation in Covid-19: a systematic review of 182 cases with encephalitis, acute disseminated encephalomyelitis, and necrotizing encephalopathies

Rev Neurosci. 2021 Sep 17;33(4):397-412. doi: 10.1515/revneuro-2021-0082. Print 2022 Jun 27.


Growing evidence demonstrates the association of encephalitis, meningoencephalitis or encephalomyelitis, with SARS-CoV-2 infection. This study aims to determine the profile and possible mechanisms behind CNS inflammatory diseases in the context of Covid-19. We conducted a systematic review of case reports on Covid-19-related encephalitis, meningoencephalitis, acute necrotizing encephalitis, and acute disseminated encephalomyelitis in adults, published before January 2021. A total of 182 cases (encephalitis = 109, meningoencephalitis = 26, acute disseminated encephalomyelitis = 35, acute necrotizing (hemorrhagic) encephalitis = 12) were included. While cerebrospinal fluid (CSF) pleocytosis and increased protein level was present in less than 50%, magnetic resonance imaging (MRI) and electroencephalogram (EEG) were abnormal in 78 and 93.2% of all cases, respectively. Viral particles were detected in cerebrospinal fluid of only 13 patients and autoantibodies were present in seven patients. All patients presented with altered mental status, either in the form of impaired consciousness or psychological/cognitive decline. Seizure, cranial nerve signs, motor, and reflex abnormalities were among associated symptoms. Covid-19-associated encephalitis presents with a distinctive profile requiring thorough diagnosis and thereby a comprehensive knowledge of the disease. The clinical profile of brain inflammation in Covid-19 exhibits majority of abnormal imaging and electroencephalography findings with mild/moderate pleocytosis or proteinorrhachia as prevalent as normal cerebrospinal fluid (CSF). Oligoclonal bands and autoantibody assessments are useful in further evaluating neuro-covid patients, as supported by our pooled evidence. Despite the possibility that direct viral invasion cannot be easily estimated, it is still more likely that immune-mediated or autoimmune reactions play a more important role in SARS-CoV-2 neuroinflammation.

Keywords: CNS inflammation; SARS-CoV-2; acute necrotizing encephalitis; autoimmune encephalitis; viral encephalitis.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Brain Diseases*
  • COVID-19* / complications
  • Encephalitis*
  • Encephalomyelitis, Acute Disseminated*
  • Humans
  • Leukocytosis
  • Meningoencephalitis*
  • Neuroinflammatory Diseases
  • SARS-CoV-2