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Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink

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To identify the key insights or developments described in this article
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Key Points

Question  Are COVID-19 vaccines associated with Guillain-Barré syndrome (GBS)?

Findings  In this cohort study of surveillance data from the Vaccine Safety Datalink that included 15.1 million doses of COVID-19 vaccines, the unadjusted incidence rate of confirmed GBS in the 1 to 21 days after receiving the Ad.26.COV2.S (Janssen) vaccine was 32.4 per 100 000 person-years, which was significantly higher than the background rate of GBS. The unadjusted incidence rate of confirmed GBS in the 1 to 21 days after mRNA vaccines was 1.3 per 100 000 person-years, which did not differ from the background rate.

Meaning  These findings suggest an increased risk of GBS after Ad.26.COV2.S vaccination.

Abstract

Importance  Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years.

Objective  To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines.

Design, Setting, and Participants  This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022.

Exposures  Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021.

Main Outcomes and Measures  GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day.

Results  From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66).

Conclusions and Relevance  In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.

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Article Information

Accepted for Publication: March 8, 2022.

Published: April 26, 2022. doi:10.1001/jamanetworkopen.2022.8879

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Hanson KE et al. JAMA Network Open.

Corresponding Author: Nicola P. Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, One Kaiser Plaza, 16th Flr, Oakland, CA 94612 (nicola.klein@kp.org).

Author Contributions: Ms Hanson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hanson, Goddard, Lewis, Fireman, Bakshi, Weintraub, Klein.

Acquisition, analysis, or interpretation of data: Hanson, Goddard, Lewis, Fireman, Myers, Bakshi, Weintraub, Donahue, Nelson, Xu, Glanz, Williams, Alpern.

Drafting of the manuscript: Hanson, Fireman, Alpern.

Critical revision of the manuscript for important intellectual content: Goddard, Lewis, Fireman, Myers, Bakshi, Weintraub, Donahue, Nelson, Xu, Glanz, Williams, Klein.

Statistical analysis: Hanson, Lewis, Fireman, Weintraub, Xu, Glanz.

Obtained funding: Hanson, Goddard, Donahue, Nelson, Klein.

Administrative, technical, or material support: Hanson, Goddard, Myers, Weintraub, Donahue, Nelson.

Supervision: Goddard, Weintraub, Xu, Klein.

Conflict of Interest Disclosures: Dr Donahue reported receiving grants from Janssen Vaccines & Prevention Funding for a study unrelated to COVID-19 vaccines outside the submitted work. Dr Nelson reported receiving grants from GlaxoSmithKline (2019-2020), nonfinancial support from ACIP/CDC as a member of COVID-19 Vaccine Safety Technical Subgroup, and grants from Moderna as a member of mRNA-1273 (COVID-19 vaccine candidate) External Safety Advisory Board for Moderna's COVID-19 vaccine program outside the submitted work. Dr Klein reported receiving grants from Pfizer research support for COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work. Dr Alpern reported receiving funding from Arnold Ventures for unrelated work. No other disclosures were reported.

Funding/Support: This study was supported by the Centers for Disease Control and Prevention (CDC), contract number 200-2012-53587-0014.

Role of the Funder/Sponsor: The study sponsor, CDC, participated as a co-investigator and contributed to protocol development; conduct of the study; interpretation of the data; review and revision of the manuscript; approval of the manuscript through official CDC scientific clearance processes; and the decision to submit the manuscript for publication. CDC authors must receive approval through the CDC scientific clearance process to submit an article for publication. Final decision to submit rests with the first author. The study sponsor does not have the right to direct the submission to a particular journal.

Disclaimer: The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the CDC. Mention of a product or company name is for identification purposes only and does not constitute endorsement by the CDC.

Additional Contributions: We thank Ousseny Zerbo, PhD (Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California) for contributions to study design and concurrent comparator analyses. We thank Burney Kieke, MA (Marshfield Clinic Research Institute) for contributions to observed-to-expected analyses. We thank Malini DeSilva, MD (HealthPartners Institute), Elyse Kharbanda, MD, MPH (HealthPartners Institute), and Allison Naleway, PhD (Center for Health Research, Kaiser Permanente Northwest) for oversight of data collection and interpretation of data. We thank Rachael Burganowski, MS (Kaiser Permanente Washington Health Research Institute), Bradley Crane, MS (Center for Health Research, Kaiser Permanente Northwest), Sungching Glenn, MS (Research and Evaluation, Kaiser Permanente Southern California), Tat’Yana Kenigsberg, MPH (Immunization Safety Office, Centers for Disease Control and Prevention), Yingbo Lou, MS (Ambulatory Care Services, Denver Health), John Mayer, PhD (Marshfield Clinic Research Institute), Erica Scotty, MS (Marshfield Clinic Research Institute), Gabriela Vazquez Benitez, PhD (HealthPartners Institute), Arnold Yee, BS (Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California), and Jingyi Zhu, PhD (HealthPartners Institute), for their contributions to data collection and preparation. We thank Dawn Asamura, BS (Research and Evaluation, Kaiser Permanente Southern California), Radha Bathala, MS (Research and Evaluation, Kaiser Permanente Southern California), Nancy Canul-Jauriga (Research and Evaluation, Kaiser Permanente Southern California), Alexander Carruth (Research and Evaluation, Kaiser Permanente Southern California), Jennifer Covey, BS (Kaiser Permanente Washington Health Research Institute), Susie Flores, RN (Research and Evaluation, Kaiser Permanente Southern California), Joy Gelfond (Research and Evaluation, Kaiser Permanente Southern California), Stacy Harsh, BSN, RN (Center for Health Research, Kaiser Permanente Northwest), Linda Heeren, BS (Marshfield Clinic Research Institute), Sunhea Kim, MPH (Research and Evaluation, Kaiser Permanente Southern California), Kate Kurlandsky, BA (Center for Health Systems Research, Denver Health), Jose Pio, MD, MPH (Research and Evaluation, Kaiser Permanente Southern California), Pat Ross, BA (Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California), Marycania Saparudin, MPH (Research and Evaluation, Kaiser Permanente Southern California), Karen Schenk, BA (Research and Evaluation, Kaiser Permanente Southern California), Sarah Simmons, MPH (Research and Evaluation, Kaiser Permanente Southern California), Laura Sirikulvadhana, MPH (Research and Evaluation, Kaiser Permanente Southern California), and Melena Taylor, BA (Research and Evaluation, Kaiser Permanente Southern California), for their contributions to medical record review. We also thank Laurie Aukes, RN (Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California), Jonathan Block, MEd (Ambulatory Care Services, Denver Health), Cheryl Carlson, MPH (Research and Evaluation, Kaiser Permanente Southern California), Stephanie Irving, MHS (Center for Health Research, Kaiser Permanente Northwest), Mara Kalter, MA (Center for Health Research, Kaiser Permanente Northwest), Tia Kauffman, MPH (Center for Health Research, Kaiser Permanente Northwest), Erika Kiniry, MPH (Kaiser Permanente Washington Health Research Institute), Leslie Kuckler, MPH (HealthPartners Institute), Denison Ryan, MPH (Research and Evaluation, Kaiser Permanente Southern California), and Lina Sy, MPH (Research and Evaluation, Kaiser Permanente Southern California), for their contributions to overall project management. All non-CDC personnel received financial compensation through CDC Vaccine Safety Datalink grant funding for their work on this project. CDC personnel were not compensated for their role in the study.

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