Incidence of Guillain–Barré syndrome following SARS‐CoV ‐2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines

  1. Miguel García‐Grimshaw
  2. Javier Andrés Galnares‐Olalde
  3. Omar Yaxmehen Bello‐Chavolla
  4. Anaclara Michel‐Chávez
  5. Arturo Cadena‐Fernández
  6. María Eugenia Briseño‐Godínez
  7. Neftali Eduardo Antonio‐Villa
  8. Isaac Núñez
  9. Alonso Gutiérrez‐Romero
  10. Laura Hernández‐Vanegas
  11. María del Mar Saniger‐Alba
  12. Roger Carrillo‐Mezo
  13. Santa Elizabeth Ceballos‐Liceaga
  14. Guillermo Carbajal‐Sandoval
  15. Fernando Daniel Flores‐Silva
  16. José Luis Díaz‐Ortega
  17. Ricardo Cortes‐Alcalá
  18. José Rogelio Pérez‐Padilla
  19. Hugo López‐Gatell
  20. Erwin Chiquete
  21. Gustavo Reyes‐Terán
  22. Antonio Arauz
  23. Sergio Iván Valdés‐Ferrer

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Abstract

Background and purpose

Information on Guillain–Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS‐CoV‐2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti‐SARS‐CoV‐2 vaccines between December 24, 2020, and October 29, 2021, in Mexico.

Methods

Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA‐based (mRNA‐1273 and BNT162b2), adenovirus‐vectored (ChAdOx1 nCov‐19, rAd26‐rAd5, Ad5‐nCoV, and Ad26.COV2‐S), and inactivated whole‐virion‐vectored (CoronaVac) vaccines.

Results

We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33–60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97–1.45), with incidence higher among Ad26.COV2‐S (3.86/1,000,000 doses, 95% CI 1.50–9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36–2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3–17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID‐19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy‐five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently.

Conclusions

Guillain–Barré syndrome was an extremely infrequent AEFI against SARS‐CoV‐2. The protection provided by these vaccines outweighs the risk of developing GBS.

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  1. Version published to 10.1111/ene.15504
  2. ScreenIT

    SciScore for 10.1101/2022.04.11.22273754: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: 18,19 Standard protocol approvals, registrations, and patient consents: The study was reviewed and approved by the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (ID: NER-3903-21-23-1) Ethics and Research Committees who waived the need for signed informed consent due to its observational nature and usage of an anonymized database.
    Consent: 18,19 Standard protocol approvals, registrations, and patient consents: The study was reviewed and approved by the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (ID: NER-3903-21-23-1) Ethics and Research Committees who waived the need for signed informed consent due to its observational nature and usage of an anonymized database.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisA statistical power calculation was not required since this is a registry-based analysis.

    Table 2: Resources

    Antibodies
    SentencesResources
    Due to limited access, testing for anti-ganglioside antibodies was not routinely performed.
    anti-ganglioside
    suggested: None
    Software and Algorithms
    SentencesResources
    28,29 Analyses were performed using IBM SPSS Statistics version 26
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    6 (IBM Corp., Armonk, NY, USA) and figures were created using GraphPad Prism, version 9 (GraphPad Software, La Jolla, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: We detected the following sentences addressing limitations in the study:
    This report has strengths and limitations. Among the strengths of our manuscript, we relied on an unusually large population of vaccine recipients and included vaccines for which no safety data related to GBS has been reported, including Ad5-nCoV, rAd26-rAd5, and CoronaVac. We would also like to acknowledge some limitations that must be considered to adequately interpret our results. First, interpretation of the study is limited by its descriptive nature. Second, we were unable to estimate incidence rate ratios or adjust incidences by age, sex, or calculate an incidence during pregnancy because we could not obtain the number of administered doses per month, sex, or age group. Third, as AEFI reports rely upon local health care providers, we could not establish causality or accurately determine other relevant clinical data, such as the development of dysautonomia, due to a lack of standardized diagnostic protocols. Fourth, due to the passive nature of the Mexican epidemiological surveillance system, which is less likely to detect cases than active surveillance systems–due to healthcare seeking bias–and because we only included patients evaluated by the ad-hoc committee, our data is susceptible to selection bias. Finally, in line with the former, mildly symptomatic patients presenting (GBS disability score < 2) presenting with non-disabling symptoms or sequelae may be underdiagnosed or underreported, as well as those occurring in rural settings with limited access to medical ser...

    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

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  3. Version published to 10.1101/2022.04.11.22273754 on medRxiv