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 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

doi:10.1016/j.vaccine.2022.06.010

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

Research output: Contribution to journal › Article › peer-review

19 Citations (SciVal)

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 language	English
Pages (from-to)	4479-4487
Number of pages	9
Journal	Vaccine
Volume	40
Issue number	32
Early online date	15 Jul 2022
DOIs	https://doi.org/10.1016/j.vaccine.2022.06.010
Publication status	Published - 30 Jul 2022
Externally published	Yes

Bibliographical note

Funding

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 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.]. 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. This work uses data provided by patients and collected by the NHS as part of their care and support (http://www.usemydata.org). We are very grateful for all the support received from the TPP Technical Operations team throughout this work, and for generous assistance from the information governance and database teams at NHS England/NHSX. Funding, 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.

Keywords

2019-nCoV Vaccine mRNA-1273
BNT162 Vaccine
Bell Palsy/chemically induced
COVID-19/prevention & control
COVID-19 Vaccines/adverse effects
ChAdOx1 nCoV-19
England
Facial Paralysis/chemically induced
Guillain-Barre Syndrome/chemically induced
Humans
Myelitis, Transverse/complications
Vaccination/adverse effects

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Walker, J. L., Schultze, A., Tazare, J., Tamborska, A., Singh, B., Donegan, K., Stowe, J., Morton, C. E., Hulme, W. J., Curtis, H. J., Williamson, E. J., Mehrkar, A., Eggo, R. M., Rentsch, C. T., Mathur, R., Bacon, S., Walker, A. J., Davy, S., Evans, D., ... McDonald, H. I. (2022). Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform. Vaccine, 40(32), 4479-4487. https://doi.org/10.1016/j.vaccine.2022.06.010

Walker, JL, Schultze, A, Tazare, J, Tamborska, A, Singh, B, Donegan, K, Stowe, J, Morton, CE, Hulme, WJ, Curtis, HJ, Williamson, EJ, Mehrkar, A, Eggo, RM, Rentsch, CT, Mathur, R, Bacon, S, Walker, AJ, Davy, S, Evans, D, Inglesby, P, Hickman, G, MacKenna, B, Tomlinson, L, Green, ACA, Fisher, L, Cockburn, J, Parry, J, Hester, F, Harper, S, Bates, C, Evans, SJW, Solomon, T, Andrews, NJ, Douglas, IJ, Goldacre, B, Smeeth, L & McDonald, HI 2022, 'Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform', Vaccine, vol. 40, no. 32, pp. 4479-4487. https://doi.org/10.1016/j.vaccine.2022.06.010

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

abstract = "INTRODUCTION: We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barr{\'e} 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-Barr{\'e} syndrome and Bell's palsy after first dose of ChAdOx1 vaccine. The absolute risk, assuming a causal effect attributable to vaccination, was low.",

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

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T1 - Safety of COVID-19 vaccination and acute neurological events

T2 - A self-controlled case series in England using the OpenSAFELY platform

AU - Walker, Jemma L

AU - Schultze, Anna

AU - Tazare, John

AU - Tamborska, Arina

AU - Singh, Bhagteshwar

AU - Donegan, Katherine

AU - Stowe, Julia

AU - Morton, Caroline E

AU - Hulme, William J

AU - Curtis, Helen J

AU - Williamson, Elizabeth J

AU - Mehrkar, Amir

AU - Eggo, Rosalind M

AU - Rentsch, Christopher T

AU - Mathur, Rohini

AU - Bacon, Sebastian

AU - Walker, Alex J

AU - Davy, Simon

AU - Evans, David

AU - Inglesby, Peter

AU - Hickman, George

AU - MacKenna, Brian

AU - Tomlinson, Laurie

AU - Green, Amelia CA

AU - Fisher, Louis

AU - Cockburn, Jonathan

AU - Parry, John

AU - Hester, Frank

AU - Harper, Sam

AU - Bates, Christopher

AU - Evans, Stephen JW

AU - Solomon, Tom

AU - Andrews, Nick J

AU - Douglas, Ian J

AU - Goldacre, Ben

AU - Smeeth, Liam

AU - McDonald, Helen I

PY - 2022/7/30

Y1 - 2022/7/30

N2 - 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.

AB - 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.

KW - 2019-nCoV Vaccine mRNA-1273

KW - BNT162 Vaccine

KW - Bell Palsy/chemically induced

KW - COVID-19/prevention & control

KW - COVID-19 Vaccines/adverse effects

KW - ChAdOx1 nCoV-19

KW - England

KW - Facial Paralysis/chemically induced

KW - Guillain-Barre Syndrome/chemically induced

KW - Humans

KW - Myelitis, Transverse/complications

KW - Vaccination/adverse effects

U2 - 10.1016/j.vaccine.2022.06.010

DO - 10.1016/j.vaccine.2022.06.010

M3 - Article

C2 - 35715350

SN - 0264-410X

VL - 40

SP - 4479

EP - 4487

JO - Vaccine

JF - Vaccine

IS - 32

ER -

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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