{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:13:39Z","timestamp":1788401619904,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Guillain\u2013Barr\u00e9 syndrome (GBS) is a rare but serious immune-mediated neurological disorder monitored as an adverse event of special interest during the COVID-19 pandemic. This study aimed to estimate the incidence of GBS following COVID-19 vaccination and SARS-CoV-2 infection and to compare the risk by vaccine platform. Methods: We conducted a population-based retrospective cohort study using data from the Valencia Health System Integrated Database (Spain) between January 2018 and March 2022. Two cohorts were defined: individuals receiving COVID-19 vaccines (mRNA-based vaccines (BNT162b2 [Pfizer\u2013BioNTech] and mRNA-1273 [Moderna]) or non-virus-vectored (NVV) adenoviral vector-based vaccines (ChAdOx1-S [AstraZeneca] and Ad26.COV2.S [Janssen])) and individuals with laboratory-confirmed SARS-CoV-2 infection. Incident GBS cases were identified within a predefined 42-day risk window following vaccination or infection. Incidence rates were calculated per 100,000 vaccine doses administered or SARS-CoV-2 infections. Results: Among 5,109,919 individuals, 4,270,610 received at least one COVID-19 vaccine dose and 920,643 experienced at least one SARS-CoV-2 infection. A total of 69 GBS cases occurred within 42 days following vaccination (incidence: 0.67 per 100,000 doses), whereas 21 cases occurred after infection (incidence: 2.20 per 100,000 infections). Incidence was lower after mRNA-based vaccines (0.55 per 100,000 doses) than after NVV vaccines (1.57 per 100,000 doses). Conclusions: This study confirms that GBS occurrence following vaccination is rare. The incidence is lower among individuals who received mRNA vaccines compared to those who received NVV vaccines. Moreover, GBS appears to be more frequent after a COVID-19 infection than after vaccination. These findings highlight the importance of integrating pharmacoepidemiological analyses with pharmacovigilance data to contextualize rare but serious adverse events.<\/jats:p>","DOI":"10.3390\/ph19030477","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:13:14Z","timestamp":1773659594000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Incidence of Guillain\u2013Barr\u00e9 Syndrome Following COVID-19 Vaccination and SARS-CoV-2 Infection: A Population-Based Cohort Study Using the Valencia Health System Integrated Database (Spain)"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0069-5652","authenticated-orcid":false,"given":"Elisa","family":"Correcher-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO\u2014Public Health), 46020 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1766-480X","authenticated-orcid":false,"given":"Sergio Pascual","family":"Viciedo-Mata","sequence":"additional","affiliation":[{"name":"Subdirectorate of Epidemiology and Public Health Surveillance, Autonomous Community of Valencia, 46020 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-9077","authenticated-orcid":false,"given":"Arantxa","family":"Urchuegu\u00eda-Fornes","sequence":"additional","affiliation":[{"name":"Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO\u2014Public Health), 46020 Valencia, Spain"},{"name":"Biomedical Research Consortium of Epidemiology and Public Health (CIBER-ESP), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5725-8972","authenticated-orcid":false,"given":"Juan Jos\u00e9","family":"Carreras","sequence":"additional","affiliation":[{"name":"Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO\u2014Public Health), 46020 Valencia, Spain"},{"name":"Biomedical Research Consortium of Epidemiology and Public Health (CIBER-ESP), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0140-6736(16)00339-1","article-title":"Guillain-Barr\u00e9 Syndrome","volume":"388","author":"Willison","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.vaccine.2010.06.003","article-title":"Guillain-Barr\u00e9 Syndrome and Fisher Syndrome: Case Definitions and Guidelines for Collection, Analysis, and Presentation of Immunization Safety Data","volume":"29","author":"Sejvar","year":"2011","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1056\/NEJMra1114525","article-title":"Guillain\u2013Barr\u00e9 Syndrome","volume":"366","author":"Yuki","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1159\/000184748","article-title":"The Epidemiology of Guillain-Barr\u00e9 Syndrome Worldwide","volume":"32","author":"McGrogan","year":"2009","journal-title":"Neuroepidemiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrneurol.2016.172","article-title":"Guillain-Barr\u00e9 Syndrome: A Century of Progress","volume":"12","author":"Goodfellow","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.autrev.2016.09.022","article-title":"Guillain\u2013Barr\u00e9 Syndrome","volume":"16","author":"Esposito","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1128\/CMR.11.3.555","article-title":"Campylobacter Species and Guillain-Barr\u00e9 Syndrome","volume":"11","author":"Nachamkin","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1212\/WNL.51.4.1110","article-title":"The Spectrum of Antecedent Infections in Guillain-Barr\u00e9 Syndrome","volume":"51","author":"Jacobs","year":"1998","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/cen3.12644","article-title":"Emerging Infectious Diseases, Vaccines and Guillain\u2013Barr\u00e9 Syndrome","volume":"12","author":"Koike","year":"2021","journal-title":"Clin. Exp. Neuroimmunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1056\/NEJMoa1605564","article-title":"Guillain\u2013Barr\u00e9 Syndrome Associated with Zika Virus Infection in Colombia","volume":"375","author":"Parra","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/oxfordjournals.aje.a112795","article-title":"Guillain-Barre Syndrome Following Vaccination in the National Influenza Immunization Program, United States, 1976\u20131977","volume":"110","author":"Schonberger","year":"1979","journal-title":"Am. J. Epidemiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1093\/aje\/kwn310","article-title":"Investigation of the Temporal Association of Guillain-Barr\u00e9 Syndrome With Influenza Vaccine and Influenzalike Illness Using the United Kingdom General Practice Research Database","volume":"169","author":"Stowe","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"ref_13","unstructured":"World Health Organization (2020). COVID-19 Vaccines: Safety Surveillance Manual, World Health Organization."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1136\/jnnp-2020-324837","article-title":"Guillain-Barr\u00e9 Syndrome and COVID-19: An Observational Multicentre Study from Two Italian Hotspot Regions","volume":"92","author":"Filosto","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/S1474-4422(20)30221-0","article-title":"Neurological Associations of COVID-19","volume":"19","author":"Ellul","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1111\/ene.14398","article-title":"Guillain\u2013Barr\u00e9 Syndrome after SARS-CoV-2 Infection","volume":"27","author":"Kilinc","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1056\/NEJMc2009191","article-title":"Guillain\u2013Barr\u00e9 Syndrome Associated with SARS-CoV-2","volume":"382","author":"Toscano","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_18","unstructured":"European Medicines Agency (EMA) (2025, May 28). Vaxzevria (Previously COVID-19 Vaccine AstraZeneca). Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/vaxzevria."},{"key":"ref_19","unstructured":"European Medicines Agency (EMA) (2025, May 28). Jcovden (Previously COVID-19 Vaccine Janssen). Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/jcovden."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e228879","DOI":"10.1001\/jamanetworkopen.2022.8879","article-title":"Incidence of Guillain-Barr\u00e9 Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink","volume":"5","author":"Hanson","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1093\/ije\/dyz266","article-title":"Data Resource Profile: The Valencia Health System Integrated Database (VID)","volume":"49","author":"Hurtado","year":"2020","journal-title":"Int. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1038\/s41591-021-01556-7","article-title":"Neurological Complications after First Dose of COVID-19 Vaccines and SARS-CoV-2 Infection","volume":"27","author":"Patone","year":"2021","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1038\/s41598-023-30940-1","article-title":"Real-World Data on the Incidence and Risk of Guillain\u2013Barr\u00e9 Syndrome Following SARS-CoV-2 Vaccination: A Prospective Surveillance Study","volume":"13","author":"Ha","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"24561","DOI":"10.1038\/s41598-024-74729-2","article-title":"Global Burden of Vaccine-Associated Guillain-Barr\u00e9 Syndrome over 170 Countries from 1967 to 2023","volume":"14","author":"Jeong","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rzymski, P. (2023). Guillain-Barr\u00e9 Syndrome and COVID-19 Vaccines: Focus on Adenoviral Vectors. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1183258"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2023054","DOI":"10.4178\/epih.e2023054","article-title":"Barriers to COVID-19 Vaccine Surveillance: The Issue of under-Reporting Adverse Events","volume":"45","author":"Noh","year":"2023","journal-title":"Epidemiol. Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7458","DOI":"10.1016\/j.vaccine.2020.09.072","article-title":"The Reporting Sensitivity of the Vaccine Adverse Event Reporting System (VAERS) for Anaphylaxis and for Guillain-Barr\u00e9 Syndrome","volume":"38","author":"Miller","year":"2020","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.therap.2016.02.015","article-title":"L\u2019apport de La Pharmaco-\u00c9pid\u00e9miologie \u00e0 La Pharmacovigilance","volume":"71","author":"Faillie","year":"2016","journal-title":"Therapies"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.vaccine.2022.11.031","article-title":"Background Rates of 41 Adverse Events of Special Interest for COVID-19 Vaccines in 10 European Healthcare Databases\u2014An ACCESS Cohort Study","volume":"41","author":"Willame","year":"2023","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1093\/aje\/kwae172","article-title":"Applying Two Approaches to Detect Unmeasured Confounding Due to Time-Varying Variables in a Self-Controlled Risk Interval Design Evaluating COVID-19 Vaccine Safety Signals, Using Myocarditis as a Case Example","volume":"194","author":"Bots","year":"2025","journal-title":"Am. J. Epidemiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1016\/j.vaccine.2024.03.043","article-title":"A Comparison of Four Self-Controlled Study Designs in an Analysis of COVID-19 Vaccines and Myocarditis Using Five European Databases","volume":"42","author":"Schultze","year":"2024","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107037","DOI":"10.1016\/j.ijid.2024.107037","article-title":"Risk of Herpes Zoster in Adults with SARS-CoV-2 Infection in Spain: A Population-Based, Retrospective Cohort Study","volume":"143","year":"2024","journal-title":"Int. J. Infect. 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