COVID-19, Vaccine, and Guillain-Barré Syndrome: Association or Causation.

Abstract

Guillain–Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy, which causes acute flaccid paralysis. Most cases of GBS report either a gastrointestinal or respiratory tract infection in the 3–4 weeks preceding symptom onset. Molecular mimicry between the lipopolysaccharides of the infectious organism and the glycosphingolipids or similar nerve antigens in our body triggers the immune response.[1] Martic, et al. have presented an original study on the GBS followed by coronavirus disease 2019 (COVID-19) infection, vaccination, and other precipitating factors during the pandemic in Serbia and Montenegro.[2] They retrospectively recruited 109 GBS patients between January and April 2022 into the following three groups: COVID-19 infection-associated (19 cases), COVID-19 vaccination-associated (16 cases), and other causes (74 cases). Individuals positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on polymerase chain reaction (PCR) testing were classified as COVID-19-positive. A COVID-19 infection or vaccination was considered a trigger if it occurred between 3 days and 6 weeks before symptom onset. No differences were noted in the clinical presentation, electrophysiology, or outcome between the three groups of GBS patients. Demyelinating neuropathy was the most common electrophysiological subtype, the most common vaccine associated was Sinopharm (8/16 cases), and most events occurred after the first dose. Unlike the Zika virus pandemic, epidemiological studies have not demonstrated COVID-19 infection to be associated with GBS.[3,4] Experts have argued that an increase in GBS incidence might be masked by a decrease in GBS incidence due to other infectious triggers because of better hygiene, lockdown, and social distancing.[5] Studies from Japan and Brazil have reported a decreased incidence of infectious diseases during the lockdown because of these containment measures,[6,7] thereby indirectly reducing the occurrence of GBS. The “GBS consortium,” established in India with 26 centers,[5] found a reduction in the number of GBS cases during the COVID-19 pandemic compared with the same duration in the previous year in both adult[5] and pediatric groups.[8] Similar findings were reported by an epidemiological study conducted in the United Kingdom.[3] These studies[3,5] also reported no significant differences between GBS patients triggered by COVID-19 and those without the infection. Demyelinating GBS is the most common subtype worldwide and was unsurprisingly the most common in this study as well. Older age was associated with a worse prognosis. This was also expected as increasing age is associated with worse GBS outcomes. The relative rarity of COVID-19 vaccine-induced GBS was also in accordance with global data. The authors reported 16 cases of COVID-19 vaccine-induced GBS in the background of 54.1% coverage in adults in a population of 7,806,891 people.[2] The first dose of vaccines was the most common dose implicated, with Sinopharm use associated with most cases. AstraZeneca and Covaxin were the vaccines most commonly used in India, and very few vaccine-associated GBS cases have been reported.[9] A study from Kerala showed a mildly raised incidence of GBS associated with ChAdOx1-S/nCoV-19 vaccination.[10] A retrospective study conducted in the West and North Midlands of the United Kingdom between January and June 2021 reported only 12 cases of COVID-19 vaccine-induced GBS.[11] Most of these individuals had received AstraZeneca vaccines. They reported a higher likelihood of cranial nerve involvement in such GBS cases, similar to Martic, et al.[2] It should be added that this GBS occurrence post-vaccination does not necessarily prove causation. Temporal associations do not imply causality. Also, the COVID-19 vaccine benefits far outweigh the risk of such rare side effects. Finally, the authors mention that the patients were treated with intravenous immunoglobulin (IVIg) and plasma exchange in the standard way. In our experience during the pandemic, the proportion of GBS patients receiving IVIg was significantly higher than that of those receiving plasma exchange (PLEX).[5] The reasons were probably manifold: logistical (greater physician and nursing workforce were working in COVID-19 designated facilities) and difficulty in conducting plasma exchanges within COVID-19 facilities and patient choice (considering they were without accompanying family members in the hospital). The pandemic has shown the need for high-quality prospective longitudinal studies on Guillain–Barré syndrome in low- to middle-income countries. The International Guillain–Barré Syndrome Outcome Study (IGOS) and the recently established GBS consortium in India are good models for replicating in other parts of the world.