Abstract
AbstractThe global impact of SARS-CoV-2 infection has raised concerns about secondary diseases beyond acute illness. This review explores the significance and potential underlying mechanisms of how SARS-CoV-2 infection might elicit an immune response targeting N-methyl-D-aspartate (NMDA) receptors, and its implications for autoimmune-driven neuropsychiatric manifestations. We identified 19 published case reports of NMDA receptor encephalitis associated with SARS-CoV-2 infection or vaccination by a systematic literature search. The significance of these reports was limited since it is not clear if a coincidental or causal relationship exists between SARS-CoV-2 infection or vaccination and manifestation of NMDA receptor encephalitis. The included studies were hampered by difficulties in establishing if these patients had pre-existing NMDA receptor antibodies which entered the brain by infection- or vaccination-associated transient blood-brain barrier leakage. In addition, four cases had comorbid ovarian teratoma, which is a known trigger for development of NMDA receptor encephalitis. Considering that billions of people have contracted COVID-19 or have been vaccinated against this virus, the publication of only 19 case reports with a possible link to NMDA receptor encephalitis, indicates that it is rare. In conclusion, these findings do not support the case that SARS-CoV-2 infection or vaccination led to an increase of existing or de novo encephalitis mediated by an autoimmune response targeting NMDA receptor function. Nevertheless, this work underscores the importance of ongoing vigilance in monitoring viral outbreaks and their potential impact on the central nervous system through basic, epidemiological and translational research.
Funder
European Research Area Network (ERA-NET) NEURON “Translational Biomarkers in Brain Disorders”
Publisher
Springer Science and Business Media LLC
Reference113 articles.
1. Worldometer; COVID-19 Coronavirus Pandemic https://www.worldometers.info/coronavirus.
2. COVID-19 Dashboard - by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. COVID-19 Map. https://coronavirus.jhu.edu/map.html. In: Center JHCR (ed).
3. Davis A COVID Evaluation Model Estimates 57 Percent of World Population Infected at Least Once. https://www.newsweek.com/covid-evaluation-model-estimates-57-percent-world-population-infected-least-once-1672440. Newsweek, Jan 24, edn. (2022).
4. Pulliam JRC, van Schalkwyk C, Govender N, von Gottberg A, Cohen C, Groome MJ, et al. Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa. Science. 2022;376:eabn4947.
5. Phan TT, Nguyen TB, Phung QT, Tran VT, Ho TT, Pho SP, et al. Incidence of SARS-CoV-2 infection during the Omicron variant emergence in Southern Vietnam: prior infection versus third-dose vaccination. Microbiol Spectr. 2022;10:e0117522.