COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database

  1. Ryan Y S Keh
  2. Sophie Scanlon
  3. Preeti Datta-Nemdharry
  4. Katherine Donegan
  5. Sally Cavanagh
  6. Mark Foster
  7. David Skelland
  8. James Palmer
  9. Pedro M Machado
  10. Stephen Keddie
  11. Aisling S Carr
  12. Michael P Lunn
  13. BPNS/ABN COVID-19 Vaccine GBS Study Group
  14. Hadi Manji
  15. Tim Lavin
  16. James B Lilleker
  17. David Gosal
  18. Robert DM Hadden
  19. Taylor Watson-Fargie
  20. Kathryn Brennan
  21. Andreas Themistocleous
  22. Jacquie Deeb
  23. Ana Romeiro
  24. Puja R Mehta
  25. Dimitri Kullmann
  26. James Miller
  27. Amar Elsaddig
  28. Adam Molyneux
  29. Plamen Georgiev
  30. Aaron Ben-Joseph
  31. James Holt
  32. Jacob Roelofs
  33. Fadi Alkufri
  34. David Allen
  35. Simon Shields
  36. Stephen Murphy
  37. Harri Sivasathiaseelan
  38. Richard Sylvester
  39. Abdul Al-Saleh
  40. Rhys Roberts
  41. Kannan Nithi
  42. Lahiru Handdunnethi
  43. Kate Wannop
  44. Amit Batla
  45. Anna Sadnicka
  46. Jananee Sivaganasundaram
  47. Tatyana Yermakova
  48. Ravi Dasari
  49. Graziella Quattrocchi
  50. Harriet Ball
  51. Rebecca Cooper
  52. Daniel Whittam
  53. Mohanned Mustafa
  54. Gabriel Yiin
  55. Shayan Ashjaei
  56. Andrew J Westwood
  57. Michelle Dsouza
  58. Eng Chuan Foo
  59. Shwe Zin Tun
  60. Khine Khine Lwin
  61. Gorande Kanabar

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS), and an association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service data in England and a multicentre surveillance study from UK hospitals to investigate the relationship between COVID-19 vaccination and GBS.

Firstly, case dates of GBS identified retrospectively in the National Immunoglobulin Database from 8 December 2021 to 8 July 2021 were linked to receipt dates of COVID-19 vaccines using data from the National Immunisation Management System in England. For the linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK-wide (four nations) GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database. For this multicentre UK-wide surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS.

Nine hundred and ninety-six GBS cases were recorded in the National Immunoglobulin Database from January to October 2021. A spike of GBS cases above the 2016–2020 average occurred in March–April 2021. One hundred and ninety-eight GBS cases occurred within 6 weeks of the first-dose COVID-19 vaccination in England [0.618 cases per 100,000 vaccinations; 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer) and one mRNA-1273 (Moderna)]. The 6-week excess of GBS (compared to the baseline rate of GBS cases 6–12 weeks after vaccination) occurred with a peak at 24 days post-vaccination; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases from January–July 2021 was between 98–140 cases for first-dose ChAdOx1 nCoV-19 vaccination. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. Detailed clinical data from 121 GBS patients were reported in the separate multicentre surveillance dataset during this timeframe. No phenotypic or demographic differences identified between vaccine-associated and non-vaccinated GBS cases occurring in the same timeframe.

Analysis of the linked NID/NIMS dataset suggested that first-dose ChAdOx1 nCoV-19 vaccination is associated with an excess GBS risk of 0.576 (95% confidence interval 0.481–0.691) cases per 100 000 doses. However, examination of a multicentre surveillance dataset suggested that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19 specific first dose link warrants further study.

Article activity feed

  1. Version published to 10.1093/brain/awac067
  2. Version published to 10.1101/2021.12.14.21267418v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.12.14.21267418: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Ethics: The UK Health Research Authority was consulted and advised that the study did not require review by an NHS Research Ethics Committee, as this was an analysis of previously collected, non-identifiable anonymised data.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical Analysis: Statistical analysis was performed using STATA 1617 and R v4.0.2/ v4.0.3 (R Core Team).
    STATA
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.12.14.21267418v1 on medRxiv