Associations of Guillain-Barré syndrome with coronavirus disease 2019 vaccination: Disproportionality analysis using the World Health Organization pharmacovigilance database

Abstract

Vaccinations against the severe acute respiratory syndrome coronavirus 2 which causes COVID-19 have been administered worldwide. We aimed to investigate associations of COVID-19 vaccination with the occurrence of Guillain-Barré syndrome (GBS). We explored potential safety signals regarding the development of GBS using disproportionality analyses to compare COVID-19 vaccination with all adverse drug reaction (ADR) reports and influenza vaccines reported to VigiBase. As of October 15, 2021, a total of 2163 cases (0.13%) of GBS and its variants (including 46 cases of Miller-Fisher syndrome and 13 cases of Bickerstaff's encephalitis) were identified in entire ADR database after vaccination with the ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, UK) or the two messenger RNA-based COVID-19 (BNT162b2; Pfizer and BioNTech) or mRNA-1273; Moderna) vaccines. The median time to onset of GBS after vaccination was around 2 weeks. The ChAdOx1 nCoV-19 and two messenger RNA-based COVID-19 vaccines demonstrated a higher risk for GBS against entire database (information component [IC]₀₂₅ = 1.73 reporting odds ratio [ROR]₀₂₅ = 3.51; IC₀₂₅ = 1.07, ROR₀₂₅ = 2.22, respectively). When compared with influenza vaccines, neither the ChAdOx1 nCoV-19 nor mRNA-based vaccines were found to be associated with greater risks of GBS (IC₀₂₅ = -1.84, ROR₀₂₅ = 0.11; IC₀₂₅ = -1.86, ROR₀₂₅ = 0.06, respectively). Although potential safety signals associated with GBS COVID-19 vaccines have been identified, the risk of GBS from COVID-19 vaccines were low and did not surpass those of influenza vaccines; however, because of the heterogeneity of the sources of information in the WHO pharmacovigilance database, further epidemiological studies are warranted to confirm these observations.

Keywords: COVID-19; Guillain-Barré syndrome; Guillain-Barré syndrome variants; SARS-CoV-2; vaccination.

FIGURE 1

The time interval from vaccination to the onset of neurological symptoms of Guillain‐Barré syndrome. Only data from patients who developed the disease within 6 weeks of vaccination were used for analyses. The median time to the onset of Guillain‐Barré syndrome (defined by broad definitions) was around 2 weeks from vaccination. Box plot indicates median number of Guillain‐Barré syndrome cases (one case per filled point) and interquartile range per week depending on the type of vaccine. The time to onset of Guillain‐Barré syndrome in patients who were vaccinated with ChAdOx1 nCoV‐19 was significantly prolonged relative to that among those who received BNT162b2 or mRNA‐1273

FIGURE 2

Forest plot with the odds ratios and information component values of mRNA‐based (BNT162b2, mRNA‐1273) and ChAdOx1 nCoV‐19 vaccine‐related Guillain‐Barré syndrome vs those of the entire VigiBase database and influenza vaccines. Compared with the entire database, COVID‐19 vaccines, mRNA‐based vaccines, and ChAdOx1 nCoV‐19 vaccine showed significantly positive associations with Guillain‐Barré syndrome. However, there were no significant positive associations in comparison with influenza vaccines. ADR, adverse drug reaction