Immune-mediated neurologic events may include Guillain-Barre syndrome or

Risk associated with SARS-CoV-2 vaccination and Guillain-Barré syndrome (GBS) — or possibly with Bell’s palsy — is slight and shouldn’t change vaccine recommendations, reviewers concluded.

An analysis of 69 papers on neuro-immunologic disease and COVID vaccines showed that 11 studies specifically assessed relationships with GBS, reported Hans-Peter Hartung, MD, of University Hospital Düsseldorf in Germany, and co-authors in JAMA Neurologyopens in a new tab or window.

Ten of these studies found links between GBS and the adenoviral vector vaccines from Johnson & Johnson (Ad.26.COV2.S) or AstraZeneca (ChAdOx1). One also reported an association between GBS and Pfizer’s BNT162b2 mRNA vaccine (Comirnaty). One study showed no connection between GBS and COVID vaccination.

Of four studies that analyzed the occurrence of Bell’s palsy after vaccination, the relationship was unclear.

GBS is an acquired demyelinating polyneuropathy that often begins in the lower extremities and ascends over time with loss of reflexes, causing muscle weakness, or in the most severe cases, paralysis. Some cases start a few days or weeks after respiratory or gastrointestinal viral infection. Often, GBS is reversible.

“GBS remains the neurological condition with the clearest evidence of a causal link with SARS-CoV-2 vaccination,” Hartung and colleagues wrote. “However, neither SARS-CoV-2 nor adenoviruses have been convincingly associated with GBS pathogenesis.”

“In general, evidence that vaccination is causally significant in the pathogenesis of autoimmune neurological syndromes is rarely validated even by large, well-conducted epidemiological studies,” with the exception being vaccine-associated immune thrombosis and thrombocytopenia (VITT)opens in a new tab or window, a rare, specific complication mainly associated with adenoviral vector vaccines, the researchers noted.

“An increased risk of developing other neurological autoimmune disorders has been extensively sought, but only the very low incidence of GBS following adenoviral vector vaccine administration has been supported by significant evidence,” they pointed out.

In June 2021, reports from two countries detailed cases of an unusual variant of GBSopens in a new tab or window associated with the AstraZeneca COVID vaccine. In July 2021, the FDA issued a warningopens in a new tab or window that Johnson & Johnson’s COVID-19 vaccine may trigger GBS in a small number of people.

An analysis of surveillance data in 2022 from the Vaccine Safety Datalink showed the overall risk of GBS was low, but unusually highopens in a new tab or window after the Johnson & Johnson shot. In May 2023, Johnson & Johnson’s Janssen unit requested the voluntary withdrawalopens in a new tab or window of its emergency use authorization for its adenoviral vector COVID vaccine in the U.S., saying the company did not intend to update the shot to address emerging variants.

Hartung and co-authors evaluated 69 unique articles about neurologic disease occurrence or worsening after SARS-CoV-2 vaccination. Neurologic disease included central and peripheral nervous system complications, including autoimmune diseases. Risks were measured against expected or background rates.

In the 11 studies that examined GBS occurrence, the post-vaccination window spanned from 0 to 42 days. In a retrospective study in Mexicoopens in a new tab or window, an association emerged between GBS and the Pfizer vaccine. A case series analysis in the U.K. and Spain showed no relationship between GBS and either adenoviral vector or mRNA vaccination.

Four studies in the analysis assessed Bell’s palsy risk. The window after vaccination ranged from 1 to 30 days, and the association between COVID vaccines and Bell’s palsy “was unclear,” Hartung and colleagues wrote.

The phase III mRNA vaccine trials identified a numerical imbalance of Bell’s palsy in the vaccinated group compared with placebo, they noted. This concern was investigated in the World Health Organization’s VigiBaseopens in a new tab or window, which showed mRNA vaccines did not have a higher reported rate of facial paralysis compared with other viral vaccines. “This finding of no association was supported by an interim analysis of surveillance dataopens in a new tab or window from 6.2 million individuals in the U.S. vaccinated with 11.8 million doses of mRNA vaccine,” the researchers said.

Hartung’s team also reported that other studies in their analysis found no quantifiable excess risk for myasthenia gravis, multiple sclerosis, or neuromyelitis optica spectrum disorders.

All studies in their review had substantial confounding factors, the researchers acknowledged. “Vaccination of a substantial proportion of the world’s population happened after a year of severe pandemic illness and restricted interperson mixing, with background health and environmental risk substantially modifying health and immune exposures,” they wrote.

“The global search for a vaccine solution was met in many quarters by suspicion and criticism of new technology,” they added. Physicians, the public, and politicians were motivated to report perceived complications, and it’s “very unlikely that the risks of vaccination for any associated condition have been underestimated.”