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. 2022 Mar 16:376:e068373.
doi: 10.1136/bmj-2021-068373.

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

Xintong Li  1 , Berta Raventós  2   3 , Elena Roel  2   3 , Andrea Pistillo  2 , Eugenia Martinez-Hernandez  4 , Antonella Delmestri  1 , Carlen Reyes  2 , Victoria Strauss  1 , Daniel Prieto-Alhambra  5   6 , Edward Burn  1   2 , Talita Duarte-Salles  2
Affiliations

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

Xintong Li et al. BMJ. .

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.

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Conflict of interest statement

Contributors: XL and BR are joint first authors. DP-A, EB, and TD-S are joint senior authors. XL, BR, DP-A, TD-S, EB, and VS conceived the study and contributed to the study design. XL, BR, ER, and AP conducted the statistical analyses. XL, BR, ER, VS, DP-A, EB, and TD-S interpreted the results and wrote the manuscript. All authors contributed to writing the manuscript, approved the final version, and had final responsibility for the decision to submit for publication. TD-S, EB, and DP-A are guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Competing interests: All authors have completed the ICMJE disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare the following interests: DP-A receives funding from the UK National Institute for Health Research (NIHR) in the form of a senior research fellowship and from the Oxford NIHR Biomedical Research Centre. XL receives the Clarendon Fund and Brasenose College scholarship (University of Oxford) to support her DPhil study. DP-A’s research group has received research grants from the European Medicines Agency; the Innovative Medicines Initiative; and Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, AstraZeneca, and UCB Biopharma.

Figures

Fig 1
Fig 1
Study design. Potential risk period (dark blue) for vaccination cohorts was defined as time between the start of the vaccination campaign and one week before the end of data availability for each database (CPRD AURUM: 8 December 2020 to 2 May 2021; SIDIAP: 27 December 2020 to 23 June 2021). For the SARS-CoV-2 infected cohort, the potential risk period started on 1 September 2020. The baseline period for the self-controlled case series analysis (light blue) was defined from 1 January 2017 to 21 days before the day of vaccination or SARS-CoV-2 positive test result. The pre-risk period (pink) was defined as −21 to −1 days before vaccination or SARS-CoV-2 positive test result, and the risk period (orange) was defined as 1 to 21 days after vaccination and 1-90 days after a SARS-CoV-2 positive test result
Fig 2
Fig 2
Standardised incidence ratios of immune mediated neurological disorders of special interest. CPRD AURUM=Clinical Practice Research Datalink AURUM (UK); SIDIAP=Information System for Research in Primary Care (Spain)
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Comment in

References

    1. WHO. COVID-19 Dashboard. Geneva: World Health Organization, 2020. https://covid19.who.int (accessed 14 January 2022).
    1. European Medicines Agency. COVID-19 vaccines: authorised. www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/cor... (accessed 14 January 2022).
    1. Polack FP, Thomas SJ, Kitchin N, et al. C4591001 Clinical Trial Group . Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 2020;383:2603-15. 10.1056/NEJMoa2034577. - DOI - PMC - PubMed
    1. Baden LR, El Sahly HM, Essink B, et al. COVE Study Group . Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med 2021;384:403-16. 10.1056/NEJMoa2035389. - DOI - PMC - PubMed
    1. Voysey M, Clemens SAC, Madhi SA, et al. Oxford COVID Vaccine Trial Group . Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99-111. 10.1016/S0140-6736(20)32661-1. - DOI - PMC - PubMed

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