Post-marketing active surveillance of Guillain Barré Syndrome following COVID-19 vaccination in persons aged ≥12 years in Italy: A multi-database self-controlled case series study

Cristina Morciano; Stefania Spila Alegiani; Francesca Menniti Ippolito; Valeria Belleudi; Gianluca Trifirò; Giovanna Zanoni; Aurora Puccini; Ester Sapigni; Nadia Mores; Olivia Leoni; Giuseppe Monaco; Elena Clagnan; Cristina Zappetti; Emanuela Bovo; Maria Cutillo; Roberto Da Cas; Marco Massari

doi:10.1371/journal.pone.0290879

Post-marketing active surveillance of Guillain Barré Syndrome following COVID-19 vaccination in persons aged ≥12 years in Italy: A multi-database self-controlled case series study

PLoS One. 2024 Jan 19;19(1):e0290879. doi: 10.1371/journal.pone.0290879. eCollection 2024.

Authors

Cristina Morciano¹, Stefania Spila Alegiani¹, Francesca Menniti Ippolito¹, Valeria Belleudi², Gianluca Trifirò³, Giovanna Zanoni⁴, Aurora Puccini⁵, Ester Sapigni⁵, Nadia Mores⁶, Olivia Leoni⁷, Giuseppe Monaco⁷, Elena Clagnan⁸, Cristina Zappetti⁹, Emanuela Bovo¹⁰, Maria Cutillo¹, Roberto Da Cas¹, Marco Massari¹

Affiliations

¹ Pharmacoepidemiology and Pharmacosurveillance Unit, National Centre for Drug Research and Evaluation, Istituto Superiore di Sanità (National Institute of Health), Rome, Italy.
² Department of Epidemiology ASL Roma 1, Lazio Regional Health Service, Rome, Italy.
³ Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
⁴ Immunology Unit, University Hospital, Verona, Italy.
⁵ Hospital Assistance Service, General Directorate for Personal Care, Health and Welfare, Emilia-Romagna Region, Bologna, Italy.
⁶ Institute of Pharmacology, Pharmacovigilance, Policlinico Universitario A. Gemelli, Catholic University of Sacred Heart, Rome, Italy.
⁷ Department of Health of Lombardy Region, Epidemiology Observatory, Milan, Italy.
⁸ Regional Health Authority, Friuli Venezia Giulia Region, Udine, Italy.
⁹ Central Directorate for Health, Social Policies, Friuli Venezia Giulia Region, Trieste, Italy.
¹⁰ Veneto Tumour Registry, Azienda Zero, Padova, Italy.

Abstract

Background: Recently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy.

Methods: Study population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020-30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods.

Results: Increased risk of GBS was found after first (RI = 6.83; 95% CI 2.14-21.85) and second dose (RI = 7.41; 2.35-23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88-14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08-31.03) and second dose (RI = 7.71; 2.38-24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40-59 (RI = 4.50; 1.37-14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56-18.28).

Conclusions: mRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events.

Copyright: © 2024 Morciano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

2019-nCoV Vaccine mRNA-1273
Ad26COVS1
BNT162 Vaccine
COVID-19 Vaccines* / adverse effects
COVID-19* / complications
COVID-19* / epidemiology
COVID-19* / prevention & control
ChAdOx1 nCoV-19
Guillain-Barre Syndrome* / epidemiology
Guillain-Barre Syndrome* / etiology
Humans
Italy / epidemiology
Product Surveillance, Postmarketing
Vaccination / adverse effects

Substances

2019-nCoV Vaccine mRNA-1273
Ad26COVS1
BNT162 Vaccine
ChAdOx1 nCoV-19
COVID-19 Vaccines

Grants and funding

The Istituto Superiore di Sanità received funding from AIFA (Italian Medicines Agency) www.aifa.gov.it for this study in the framework of the collaboration agreement “Efficacia real world e sicurezza dei vaccini anti Covid-19: studio di coorte e Self-Controlled Case Series” (Effectiveness and safety of COVID-19 vaccines: cohort and Self-Controlled Case Series studies). AIFA is the Italian national regulatory body for drugs and vaccines and a public organization. All authors are independent from the funder. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.