Study shows slight increase in Guillain-Barre syndrome risk with adenovirus COVID vaccines

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Jan 16 2024

A new paper in the journal JAMA Neurology examines whether coronavirus disease 2019 (COVID-19) vaccines cause or exacerbate autoimmune and neurological diseases.

Study: SARS-CoV-2 Vaccination and Neuroimmunological Disease: A Review. Image Credit: Tirachard Kumtanom / Shutterstock.com

Rare side effects of COVID-19 vaccines

The COVID-19 pandemic was declared in March 2020 and was subsequently accompanied by restrictions on public interactions and travel in an attempt to limit the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Many different vaccine platforms were developed to combat COVID-19, including adenovirus vector- and messenger ribonucleic acid (mRNA)-based vaccines to introduce the viral spike protein, the primary immunogen, into the human body. The novelty of mRNA vaccines led to many concerns about the possibility of unforeseen neurological sequelae, such as Guillain-Barre syndrome (GBS), which is an acute autoimmune disease affecting multiple nerve roots causing sudden paralysis.

Most epidemiological studies have failed to provide evidence of the role of vaccines in neuroimmunological disease. Nevertheless, vaccine-associated immune thrombosis and thrombocytopenia (VITT), characterized by cerebral venous sinus thrombosis, have been identified to be caused specifically by the Oxford-AstraZeneca and Janssen adenovirus vector COVID-19 vaccines. These rare side effects have been reported in up to 15 people for every one million after the first dose of an adenovirus vaccine.

What did the study show?

The researchers used data from multiple international studies to examine the potential for a link between COVID-19 vaccines and the incidence of GBS. To this end, adenovirus vector vaccines were associated with an increased risk of GBS.

One United Kingdom study reported a three-times greater risk of admission or death from GBS following Oxford adenovirus vaccine administration. Moreover, the risk of developing GBS within one to 1.5 months of vaccination was increased to about 30 cases for every one million vaccination doses. Most cases occurred after the first dose.

This link was not observable with the Pfizer mRNA vaccine.

The U.K. National Immunoglobulin Database/NHSE IVIG identified a maximum of 140 cases of GBS in excess of the expected number, peaking 24 days from the first dose of the Oxford vaccine. The excess risk was about 0.6 cases for every 100,000 vaccine doses. However, a prospective study covering many centers in the U.K. failed to identify any GBS cases post-vaccination.

German researchers showed a three to four-times rise in GBS cases with adenovirus vector vaccines. In France, there were six additional cases reported for every one million first doses of either adenoviral vaccines, all above 50 years of age, and including only hospitalized cases.

Small studies conducted in the United States suggest an increase in GBS rates by over 30 times. Comparatively, the Vaccine Adverse Event Reporting System (VAERS) identified an increase in incidence by 6.4 cases for every 100,000, with another study indicating an increase in GBS risk by 3.8 times.

Only one study, a large population-based cohort study from Mexico, showed a link between the Pfizer mRNA vaccine and GBS incidence, which was increased two-fold at 1.9 cases for every 100,000 doses as compared to 3.9 cases for the Oxford vaccine.

India reported an increase of up to tenfold between mid-March to mid-April 2021 in three districts of Kerala; however, the study size was small as compared to the overall vaccinated population. Another report suggested a three- to four-fold rise in GBS incidence with adenovirus vaccines as compared to mRNA vaccines after the first dose.

A potential association between mRNA vaccines and Bell’s palsy has been reported. This potential increased risk was initially reported during phase III clinical trials, during which the risk was found to be equivalent to that following the administration of other vaccines.

Other illnesses affecting the nervous system, such as myasthenia gravis or demyelinating disease of the brain or spinal cord, have not been associated with these vaccines.

It is possible that vaccination may rarely trigger a relapse or worsen symptoms or first presentation in already-diagnosed or susceptible individuals.”

What are the implications?

Current evidence indicates that there is a small increased risk of GBS following adenovirus vaccination against COVID-19. It is difficult to identify the putative autoimmune trigger; however, the spike protein does not appear to be responsible.

Mouse models have not shown autoimmunity induced by repeated injections of the recombinant SARS-CoV-2 spike protein. Thus, some other component in the adenovirus vaccine may be responsible for this autoimmune response.

Further investigation is essential to understand whether adenovirus vaccines lead to specific T-cell receptor and antibody responses in GBS cases as compared to other individuals who receive the adenovirus vaccine.

Considering the small associations observed between the COVID-19 vaccines, GBS, and Bell’s palsy, there is no reason to modify current vaccination recommendations or change guidelines for vaccinating those with pre-existing neurological disease due to autoimmune causes.