A review of the potential neurological adverse events of COVID-19 vaccines

Abstract

Despite the advantages of getting access to the coronavirus disease 2019 (COVID-19) vaccines, their potential ability to induce severe adverse events (AEs) has been a significant concern. Neurological complications are significant among the various adverse events following immunization (AEFI) due to their likely durability and debilitating sequelae. Neurological AEs following COVID-19 vaccination can either exacerbate or induce new-onset neuro-immunologic diseases, such as myasthenia gravis (MG) and Guillain-Barre syndrome (GBS). The more severe spectrum of AEs post-COVID19 vaccines has included seizures, reactivation of the varicella-zoster virus, strokes, GBS, Bell's palsy, transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM). Here, we discuss each of these neurological adverse effects separately.

Keywords: Adverse event; COVID-19; Neurologic; SARS-CoV-2; Vaccine.

Fig. 1

COVID-19 vaccine-induced Guillain–Barré syndrome. After the administration of the COVID-19 vaccine, the vaccine particles enter the body and activate APCs, which could trigger B cells and CD4⁺ T cells activation. Naïve CD4⁺ T cells are then differentiated into three subgroups, Th₁, Th₂, and Th₁₇, producing cytokines, such as IL-2, IL-4, IL-10, IL-12, IL-17A, TNF-α, and IFY-γ. Moreover, B cells are converted to plasma cells, secreting antiganglioside antibodies. These antibodies are then gone through the blood-nerve barrier, binding to the ganglioside of the myelinated motor neurons or attaching to the neuromuscular junction. As a result of forming gangliosides-antiganglioside antibody complexes, MAC and macrophages are activated, attacking and destroying the myelin. Such demyelination would decrease the speed of action potential transmission through these nerves, causing an inflammatory ascending polyradiculoneuropathy. IVIg administration could reverse these mechanisms via 2 main pathways: triggering Treg cells, inhibiting B cells and inflammatory cytokines, and dimerizing with antiganglioside antibodies. Moreover, plasmapheresis could alleviate the symptoms via actively depleting inflammatory cytokines from patients’ bloodstream. Furthermore, cysteine proteases can degrade antiganglioside antibodies, inhibiting this inflammatory neuropathy. Eculizumab and nafamostat mesylate would also inhibit MAC, alleviating the demyelination. Abbreviations: APC Antigen-presenting cell, TCR T cell receptor, MHC II Major histocompatibility complex II, BCR B cell receptor, Th T helper cell, IL-2 Interleukin-2, IL-4 Interleukin-4, IL-10 Interleukin-10, IL-12 Interleukin-12, IL-17A Interleukin-17A, TNF-α Tumor necrosis factor-α, IFY-γ Interferon-γ, GBS Guillain-Barré syndrome, IVIg Intravenous immune globulin, Treg regulatory T cell, TGF-β Transforming growth factor-β, PP Plasmapheresis, IFN-β Interferon-β, MAC Membrane attack complex