Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform

Jemma L. Walker, Anna Schultze, John Tazare, Arina Tamborska, Bhagteshwar Singh, Katherine Donegan, Julia Stowe, Caroline E. Morton, William J. Hulme, Helen J. Curtis, Elizabeth J. Williamson, Amir Mehrkar, Rosalind M. Eggo, Christopher T. Rentsch, Rohini Mathur, Sebastian Bacon, Alex J. Walker, Simon Davy, David Evans, Peter InglesbyGeorge Hickman, Brian MacKenna, Laurie Tomlinson, Amelia CA Green, Louis Fisher, Jonathan Cockburn, John Parry, Frank Hester, Sam Harper, Christopher Bates, Stephen JW Evans, Tom Solomon, Nick J. Andrews, Ian J. Douglas, Ben Goldacre, Liam Smeeth, Helen I. McDonald*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Introduction: We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barré syndrome (GBS), transverse myelitis and Bell's palsy. 

Methods: With the approval of NHS England we analysed primary care data from >17 million patients in England linked to emergency care, hospital admission and mortality records in the OpenSAFELY platform. Separately for each vaccine brand, we used a self-controlled case series design to estimate the incidence rate ratio for each outcome in the period following vaccination (4–42 days for GBS, 4–28 days for transverse myelitis and Bell's palsy) compared to a within-person baseline, using conditional Poisson regression. 

Results: Among 7,783,441 ChAdOx1 vaccinees, there was an increased rate of GBS (N = 517; incidence rate ratio 2·85; 95% CI2·33–3·47) and Bell's palsy (N = 5,350; 1·39; 1·27–1·53) following a first dose of ChAdOx1 vaccine, corresponding to 11.0 additional cases of GBS and 17.9 cases of Bell's palsy per 1 million vaccinees if causal. For GBS this applied to the first, but not the second, dose. There was no clear evidence of an association of ChAdOx1 vaccination with transverse myelitis (N = 199; 1·51; 0·96–2·37). Among 5,729,152 BNT162b2 vaccinees, there was no evidence of any association with GBS (N = 283; 1·09; 0·75–1·57), transverse myelitis (N = 109; 1·62; 0·86–3·03) or Bell's palsy (N = 3,609; 0·89; 0·76–1·03). Among 255,446 mRNA-1273 vaccine recipients there was no evidence of an association with Bell's palsy (N = 78; 0·88, 0·32–2·42). 

Conclusions: COVID-19 vaccines save lives, but it is important to understand rare adverse events. We observed a short-term increased rate of Guillain-Barré syndrome and Bell's palsy after first dose of ChAdOx1 vaccine. The absolute risk, assuming a causal effect attributable to vaccination, was low.

Original languageEnglish
Pages (from-to)4479-4487
Number of pages9
JournalVaccine
Volume40
Issue number32
Early online date7 Jun 2022
DOIs
Publication statusPublished - 30 Jul 2022

Bibliographical note

Funding Information: This study was supported by the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Vaccines and Immunisation and the NIHR HPRU in Emerging and Zoonotic Infections. The OpenSAFELY data science platform is funded by the Wellcome Trust. TPP provided pro bono technical expertise and infrastructure.

JLW, NA and HIM are funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation (NIHR200929), a partnership between UK Health Security Agency and LSHTM. AS is employed by LSHTM on a fellowship sponsored by GSK. AT is funded by the UK National Institute for Health Research via academic clinical fellowship scheme. BS is funded by the UK Medical Research Council COVID-Neuro Global programme (MR/V033441/1) and the UK National Institute for Health Research Global Health Research Group on Brain Infections (17/63/110). EW holds grants from MRC. RME is funded by HDR-UK and the MRC. RM holds a Sir Henry Wellcome Fellowship funded by the Wellcome Trust. BMK is also employed by NHS England working on medicines policy and clinical lead for primary care medicines data. KB holds a Wellcome Senior Research Fellowship (220283/Z/20/Z). TS is supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (Grant No. NIHR200907), NIHR Global Health Research Group on Brain Infections (No. 17/63/110), the UK Medical Research Council’s Global Effort on COVID-19 Programme (MR/V03). LS reports grants from Wellcome, MRC, NIHR, UKRI, British Council, GSK, British Heart Foundation, and Diabetes UK outside this work. BG’s work on better use of data in healthcare more broadly is currently funded in part by: the Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation; all DataLab staff are supported by BG’s grants on this work.

The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, UK Health Security Agency (UK HSA), Medicines and Healthcare products Regulatory Agency (MHRA) or the Department of Health and Social Care (DHSC). Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [JLW, NA and HIM are funded by the NIHR Health Protection Research Unit in Vaccines and Immunisation, a partnership between UK Health Security Agency and London School of Hygiene & Tropical Medicine. JLW and HIM have been occasional invited experts to the Commission on Human Medicines (CHM) COVID-19 Vaccines Safety Surveillance Methodologies Expert Working Group. BS received a grant from the Medical Research Council, via the UKRI/NIHR Global Effort on COVID-19 Research to study neurological disease in relation to COVID-19, and is an unpaid case management consultant to WHO-South-East Asia Region for the COVID-19 pandemic, but vaccination against the infection is not the focus in either case. KD is employed by the Medicines and Healthcare products Regulatory Agency (MHRA) which is an Executive Agency of the Department of Health and Social Care and is the UK Licensing Authority. The MHRA has statutory responsibility to monitor the safety of medicinal products, including vaccines, on the UK market. EW has received payments from AZ for providing training, unrelated to the submitted work. TS was Chair/Co-Chair of the United Kingdom Research and Innovation / National Institute for Health Research COVID-19 Rapid Response and Rolling Funding Initiatives, was an Advisor to the UK COVID-19 Therapeutics Advisory Panel and is a member of the UK Medicines and Healthcare Products Regulatory Agency COVID-19 Vaccines Benefit Risk Expert Working Group. IJD has received unrestricted research grants and holds shares in GlaxoSmithKline (GSK). BG has received research funding from the Laura and John Arnold Foundation, the NHS National Institute for Health Research (NIHR), the NIHR School of Primary Care Research, the NIHR Oxford Biomedical Research Centre, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK (HDRUK), the Health Foundation, and the World Health Organization; he also receives personal income from speaking and writing for lay audiences on the misuse of science.].

Open Access: This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0).


Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd.

Citation: Jemma L Walker, Anna Schultze, John Tazare, Arina Tamborska, Bhagteshwar Singh, Katherine Donegan, Julia Stowe, Caroline E Morton, William J Hulme, Helen J Curtis, Elizabeth J Williamson, Amir Mehrkar, Rosalind M Eggo, Christopher T Rentsch, Rohini Mathur, Sebastian Bacon, Alex J Walker, Simon Davy, David Evans, Peter Inglesby, George Hickman, Brian MacKenna, Laurie Tomlinson, Amelia CA Green, Louis Fisher, Jonathan Cockburn, John Parry, Frank Hester, Sam Harper, Christopher Bates, Stephen JW Evans, Tom Solomon, Nick J Andrews, Ian J Douglas, Ben Goldacre, Liam Smeeth, Helen I McDonald,
Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform, Vaccine, Volume 40, Issue 32, 2022, Pages 4479-4487, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2022.06.010.

DOI: https://doi.org/10.1016/j.vaccine.2022.06.010.

Keywords

  • Bell's palsy
  • COVID-19 vaccines
  • Guillain-Barré syndrome
  • Self-controlled case series
  • Transverse myelitis
  • Vaccine safety

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