Review 1: "Association between COVID-19 vaccination, infection, and risk of Guillain-Barre syndrome, Bell's palsy, encephalomyelitis and transverse myelitis: a population-based cohort and self-controlled case series analysis"

Sasha Živković

doi:doi:10.1162/2e3983f5.93b6b787

“Association between COVID-19 vaccination, infection, and risk of Guillain-Barre syndrome, Bell’s palsy, encephalomyelitis and transverse myelitis: a population-based cohort and self-controlled case series analysis”

by Xintong Li, Eugenia Martinez-Hernandez, Elena Roel Herranz, Antonella Delmestri, Talita Duarte-Salles, Victoria Strauss, Edward Burn, and Daniel Prieto-Alhambra

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dx.doi.org

Description

ABSTRACTOBJECTIVEWe aimed to study the association between COVID-19 vaccines, SARS-CoV-2 infection, and the risk of immune-mediated neurological events.METHODSDesignPopulation-based historical rate comparison study and self-controlled case series (SCCS) analysis.SettingPrimary care records from the United Kingdom.ParticipantsIndividuals who received the first dose of ChAdOx1 or BNT162b2 between 8 December 2020 and 6 March 2021. A cohort with a first positive RT-PCR test for SARS-CoV-2 between 1 September 2020 and 28 February 2021 was used for comparison.Main outcome measuresOutcomes included Guillain-Barre syndrome (GBS), Bell’s palsy, encephalomyelitis, and transverse myelitis.Incidence rates were estimated in the 28 days post first-dose vaccine, 90 days post-COVID-19, and between 2017 to 2019 for the general population cohort for background rates. Indirectly standardised incidence ratios (SIRs) were estimated. Adjusted incidence rate ratios (IRR) were estimated from the SCCS when sufficient statistical power was reached.ResultsWe included 1,868,767 ChAdOx1 and 1,661,139 BNT162b2 vaccinees; 299,311 people infected with COVID-19; and 2,290,537 from the general population. SIRs for GBS were 1.91 [95% CI: 0.86 to 4.26] after ChAdOx1, 1.29 [0.49 to 3.45] after BNT162b2, and 5.20 [1.95 to 13.85] after COVID-19. In the same cohorts, SIRs for Bell’s palsy were 1.34 [1.05 to 1.72], 1.15 [0.88 to 1.50], and 1.23 [0.80 to 1.89], and for encephalomyelitis 1.62 [0.61 to 4.31], 0.86 [0.22 to 3.46], and 11.05 [5.27 to 23.17], respectively. Transverse myelitis was too rare to analyse (n<5 in all cohorts). SCCS analysis was only conducted for Bell’s palsy due to limited statistical power. We found no association between either vaccine and Bell’s palsy, with an IRR of 1.10 [0.81 to 1.46] and 1.15 [0.87 to 1.49] for BNT162b2 and ChAdOx1, respectively.ConclusionsWe found no consistent association between either vaccine and any of the studied neuroimmune adverse events studied. Conversely, we found a 5-fold increase in risk of GBS and an 11-fold of encephalomyelitis following COVID-19.

RR:C19 Evidence Scale rating by reviewer:

Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review:

Li et al present an interesting study looking at associations between CoviD19 vaccination, infection, and 4 different neurologic complications including Guillain-Barre syndrome, Bell’s palsy, encephalomyelitis, and transverse myelitis. They have looked at incidence rates in the first 28 days post-first-dose vaccine, 90 days post Covid-19 infection, and 2 years for general population controls from the United Kingdom. Their main conclusions were that they did not find an increased risk after vaccination, but they do report a 5-fold increase in the risk of GBS and 11-fold of encephalomyelitis following Covid 19.

While this is an interesting study with valuable information, it does have some methodological limitations. Due to a small number of events, the magnitude of association between Covid19 infection and Guillain-Barre syndrome and encephalomyelitis may be overestimated. Most studies report the annual incidence of Guillain Barre syndrome as 1-2 per 100,000 person-years and the Covid19 cohort may not large enough. We also have to compare such reported risk for Guillain Barre syndrome with other situations, and a recent French study looking at the risk of Guillain Barre syndrome with influenza vaccination did not find an increased risk of GBS within 6 weeks from vaccination, but the risk was 4-fold higher after acute respiratory or gastrointestinal infections (Neurology. 2020 May 19;94(20):e2168-e2179. doi: 10.1212/WNL.0000000000009180 ). Another recent study using a different methodology did not find an increased risk of Guillain Barre syndrome with Covid 19 (publication cited by Authors in this study, ref 69). Additionally, it would be helpful if the authors would explain why did they choose the 4-week window for the vaccinated cohort versus the 90-day window for the Covid19 cohort. If the 90-day window was chosen for individuals infected with Covid19, why was the number of person-years listed as 40,596 as there were 299,203 individuals in this cohort?

We should use lectures from the past swine flu epidemics in 1976 in the US when initial studies suggested that there was a substantial increase in the risk of Guillain Barre after swine flu vaccination, and the vaccination campaign was halted. However, subsequent analyses showed that the initial studies overestimated the risk from vaccination and most of the subsequent studies showed a lower risk of Guillain Barre syndrome in vaccinated individuals when compared to unvaccinated.

Overall, this is an interesting study, but it may not be powered to capture the magnitude of risk of rare neurologic complications in patients who had Covid19 infection. The lack of increased risk of neurologic complications in larger cohorts of individuals who have received 2 types of Covid19 vaccines is re-assuring.