Association between covid-19 vaccination, SARS-CoV-2 infection, and risk of immune mediated neurological events: population based cohort and self-controlled case series analysis
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
Objective
To study the association between covid-19 vaccines, SARS-CoV-2 infection, and risk of immune mediated neurological events.
Design
Population based historical rate comparison study and self-controlled case series analysis.
Setting
Primary care records from the United Kingdom, and primary care records from Spain linked to hospital data.
Participants
8 330 497 people who received at least one dose of covid-19 vaccines ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, or Ad.26.COV2.S between the rollout of the vaccination campaigns and end of data availability (UK: 9 May 2021; Spain: 30 June 2021). The study sample also comprised a cohort of 735 870 unvaccinated individuals with a first positive reverse transcription polymerase chain reaction test result for SARS-CoV-2 from 1 September 2020, and 14 330 080 participants from the general population.
Main outcome measures
Outcomes were incidence of Bell’s palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. Incidence rates were estimated in the 21 days after the first vaccine dose, 90 days after a positive test result for SARS-CoV-2, and between 2017 and 2019 for background rates in the general population cohort. Indirectly standardised incidence ratios were estimated. Adjusted incidence rate ratios were estimated from the self-controlled case series.
Results
The study included 4 376 535 people who received ChAdOx1 nCoV-19, 3 588 318 who received BNT162b2, 244 913 who received mRNA-1273, and 120 731 who received Ad26.CoV.2; 735 870 people with SARS-CoV-2 infection; and 14 330 080 people from the general population. Overall, post-vaccine rates were consistent with expected (background) rates for Bell’s palsy, encephalomyelitis, and Guillain-Barré syndrome. Self-controlled case series was conducted only for Bell’s palsy, given limited statistical power, but with no safety signal seen for those vaccinated. Rates were, however, higher than expected after SARS-CoV-2 infection. For example, in the data from the UK, the standardised incidence ratio for Bell’s palsy was 1.33 (1.02 to 1.74), for encephalomyelitis was 6.89 (3.82 to 12.44), and for Guillain-Barré syndrome was 3.53 (1.83 to 6.77). Transverse myelitis was rare (<5 events in all vaccinated cohorts) and could not be analysed.
Conclusions
No safety signal was observed between covid-19 vaccines and the immune mediated neurological events of Bell’s palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. An increased risk of Bell’s palsy, encephalomyelitis, and Guillain-Barré syndrome was, however, observed for people with SARS-CoV-2 infection.
Article activity feed
-
Sasha Živković
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"
Reviewer: Sasha Živković (University of Pittsburgh) | 📒📒📒 ◻️◻️
-
Sasha Živković
Review of "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"
Reviewer: Sasha Živković (University of Pittsburgh) | 📒📒📒 ◻️◻️
-
-
SciScore for 10.1101/2021.09.08.21263276: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding Due to the limited number of events, we only had power to run SCCS for Bell’s Palsy (Appendix table 2).[49] Any subgroups with less than 5 people were blinded and reported as <5, following information governance requirements. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Study strengths and limitations: The main strength of our study is the population-based method with data from the UK primary care system, which …
SciScore for 10.1101/2021.09.08.21263276: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding Due to the limited number of events, we only had power to run SCCS for Bell’s Palsy (Appendix table 2).[49] Any subgroups with less than 5 people were blinded and reported as <5, following information governance requirements. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Study strengths and limitations: The main strength of our study is the population-based method with data from the UK primary care system, which have great representativeness and complete capture of vaccinations among the UK population. In addition, the use of self-controlled case series study design took the advantage of within person comparison to reduce time-fixed confounding. We also further adjusted for age and seasonality to control for time-varying confounding. Our study has limitations. As we only included primary care data, diagnoses from inpatient settings may not be captured and the absolute risk may be underestimated. However, a previous study has showed that CPRD primary care data captures immune-mediated neurological disorders like GBS accurately, even without linking hospital data.[72] Within-database comparisons are recommended when comparing observed and expected rates due to database-level heterogeneity.[43] We used CPRD Aurum and CPRD GOLD. Although both contain UK primary care data, these data come from different electronic health record clinical systems and use different medical coding. However, one study showed that the two databases generated similar estimates.[73] We used code lists and algorithms for the identification of neuro-immune events previously published as part of a study on the background rates of COVID-19 AESI.[43] Mapping to the OMOP common data model also helped maximise comparability. The short follow-up time after vaccination may have le...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
