AI-CoV Study: Autoimmune Encephalitis Associated With COVID-19 and Its Vaccines-A Systematic Review

Background And Purpose: Autoimmune encephalitis (AIE) following coronavirus disease 2019 (COVID-19) is an underexplored condition. This study aims to systematically review the clinico-investigational and pathophysiologic aspects of COVID-19 and its vaccines in association with AIE, and identify the factors predicting neurological severity and outcomes.

Methods: Relevant data sources were searched using appropriate search terms on January 15, 2022. Studies meeting the criteria for AIE having a temporal association with COVID-19 or its vaccines were included.

Results: Out of 1,894 citations, we included 61 articles comprising 88 cases: 71 of COVID-19-associated AIE, 3 of possible Bickerstaff encephalitis, and 14 of vaccine-associated AIE.There were 23 definite and 48 possible seronegative AIE cases. Anti-NMDAR (N-methyl-D-aspartate receptor; =12, 16.9%) was the most common definite AIE. Males were more commonly affected (sex ratio=1.63) in the AIE subgroup. The neurological symptoms included alteredmental state (=53, 74.6%), movement disorders (=28, 39.4%), seizures (=24, 33.8%), behavioural (=25, 35.2%), and speech disturbances (=17, 23.9%). The median latency to AIE diagnosis was 14 days (interquartile range=4-22 days). Female sex and ICU admission had higherrisks of sequelae, with odds ratio (OR) of 2.925 (95% confidence interval [CI]=1.005-8.516)and 3.515 (95% CI=1.160-10.650), respectively. Good immunotherapy response was seen in42/48 (87.5%) and 13/13 (100%) of COVID-19-associated and vaccine-associated AIE patients, respectively. Sequelae were reported in 22/60 (36.7%) COVID-19 associated and 10/13 (76.9%) vaccine-associated cases.

Conclusions: The study has revealed diagnostic, therapeutic, and pathophysiological aspects of AIE associated with COVID-19 and its vaccines, and its differences from postinfectious AIE.

Systematic Review Registration: PROSPERO registration number CRD42021299215.