Guillain-Barre syndrome and link with COVID-19 infection and vaccination: a review of literature

Abstract

Background: Guillain-Barré syndrome (GBS) is an autoimmune disease associated with significant morbidity. A wide variety of infectious and non-infectious triggers have been identified to be associated with GBS. COVID-19 has gained attention in recent years for its role in GBS pathogenesis. Our study aims to review the literature on GBS and its epidemiological and pathophysiological association with COVID-19.

Description: Recent literature on GBS associated with COVID-19 infections, such as case reports, case series, systematic reviews, and large-scale epidemiological studies, were reviewed. We also reviewed studies that included vaccines against COVID-19 in association with GBS. Studies that focused on understanding the pathobiology of GBS and its association with infectious agents including COVID-19 were reviewed.

Conclusion: Despite a lack of consensus, GBS is strongly associated with COVID-19 infection. The exact pathophysiological mechanism regarding COVID-19 as a causative agent of GBS is unknown. Mechanisms, such as the proinflammatory state, triggering of autoimmunity, and direct viral invasion, are postulated and remain to be investigated. Adenovirus vector vaccines are most likely associated with GBS, and the consensual reports clearly suggest mRNA vaccines are associated with low risk and may be protective against GBS by reducing the risk of COVID-19 infection.

Keywords: COVID-19; COVID-19 vaccine; Guillain–Barre Syndrome (GBS); autoimmune disease; peripheral nervous system.

Figure 1

Pathophysiology of COVID-19 related GBS – schematic. The three pathophysiological mechanisms for GBS associated with COVID-19 infections. Left to right: direct invasion by the virus via ACE2 receptors in the central and peripheral nervous system causing direct toxicity in cases touted to be para-infectious forms of GBS. COVID-19 infections causing a cytokine storm due to markedly elevated levels of several proinflammatory mediators, the most prominent being TNF-α, which leads to complement activation, causing macrophage-lead myelin damage, and IL-17, which directly causes Schwann cell degeneration. Both SARS-CoV-2 and adenovirus vector vaccines cause humoral-mediated autoantibody formations such as GM1, GD1a, GD1b, GQ1b, and GT1b that target gangliosides on the nervous tissue, causing disruption of anatomical and physiological barriers with three main targets on nerves: 1. Axon; 2. nodes of Ranvier; and 3. Myelin.