Mechanisms of COVID-19-induced cerebellitis

Abstract

The COVID-19 pandemic caused by SARS-CoV2 has raised several important health concerns, not least increased mortality and morbidity. SARS-CoV2 can infect the central nervous system via hematogenous or transneuronal routes, acting through different receptors including ACE2, DPP4, and neuropilin 1 and cause several issues, including the focus here, cerebellitis. The cerebellum is an essential part of the CNS located adjacent to the brainstem with a complex micro and macroscopic structure. The cerebellum plays several physiological roles, such as coordination, cognition, and executive functioning. Damage to the cerebellum can lead to incoordination and ataxia. In our narrative review, we searched different databases from 2021 to 2022 with the keywords cerebellum and COVID-19; 247 studies were identified and reviewed, focusing on clinical studies and excluding non-clinical studies; 56 studies were finally included for analysis. SARS-CoV2 infection of the cerebellum can be seen to be assessed through many methods such as MRI, PET, CT, postmortem studies, and histological findings. These methodological studies have demonstrated that cerebellar infection with COVID-19 can bring about several sequelae: thrombosis, microbleed, hemorrhage, stroke, autoantibody production, ataxia, and widespread inflammation in the cerebellum. Such central effects are likely to exacerbate the known multiorgan effects of SARS-CoV2 and should also be considered as part of disease prognosis.

Keywords:

• Cerebellum
• COVID-19
• SARS-CoV2
• ataxia
• stroke

Transparency

Declaration of funding

This article was not funded.

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

MB, SOT, MS, MMA, FN, NDN, and AM have conceived and designed the concept and road map of the study, searched the literature, and drafted the manuscript. They designed the concept map and figures. GJS has critically reviewed the manuscript for its content, originality, English language usage, and interpreted data accuracy. MSH has designed the study, helped in manuscript preparation, and critically reviewed the manuscript. He is the archival author and attests to the integrity of the original data and the analysis reported in this manuscript. All authors have made a substantive contribution to approving the final manuscript.

Acknowledgements

The authors thank Dr. Moazamehosadat Razavinasab for her critical review of this Article.