On December 20, 2020, Israel initiated a national vaccination program against COVID-19. National and international vaccine guidelines did not preclude patients who have previously been diagnosed with Guillain-Barré Syndrome (GBS) from receiving the COVID-19 vaccine.1,2 However, previous association between vaccines and GBS raises the level of caution and hesitancy among clinicians and patients regarding administering the vaccine.3-5 The aim of this study was to establish rates of GBS relapse among Pfizer-BioNTech BNT162b2 vaccine receivers.

Methods

We performed a descriptive retrospective cohort study in the second largest health maintenance organization in Israel, Maccabi Healthcare Services (MHS), serving more than 2.5 million members, representing a quarter of the Israeli population. MHS has a nationwide centralized database, spanning more than 20 years, that includes extensive clinic and hospital diagnoses as well as vaccine registries. Data from the medical records were retrieved for all members who were recorded as having an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code for GBS (code 357.0). To ensure that the correct patients with GBS diagnosis were identified, manual review of the electronic medical record was conducted of all cases. The criterion for a GBS case was a diagnosis given by a hospital neurology department. Data collected included information regarding GBS, vaccine administration, medical care encounters, and hospital visits after receiving at least 1 vaccine dose. The study was approved by the MHS institutional review board (0029-21-MHS).

Results

Seven hundred two cases of GBS were identified between 2000 and 2020. Three hundred thirty-seven (48%) were women and the mean (SD) age was 53 (18) years. Of these patients, 579 had received 1 vaccine dose and 539 received 2 doses. A median (IQR) of 108 (82 to 122) days’ follow-up was obtained after the first vaccine administration and 90 (64 to 100) after the second. Of 40 patients who received only 1 dose of vaccine, 38 had COVID-19 previously and needed only 1 dose according to Israeli Ministry of Health guidelines.1

Forty-eight of 579 patients were seen in a hospital (Table). Twenty-four had visited the emergency department and were released after less than 24 hours for transient non-neurologic concerns and the others needed admission for a variety of conditions. Only 5 were referred to the hospital for neurological concerns. Two patients had paresthesia, 1 patient had several months' duration of tremor, and 1 patient was evaluated for a seizure. They were released from the emergency department within a few hours without further medical observation. The fifth patient had a history of previously diagnosed GBS and was treated with plasmapheresis with no residual neurological symptoms. The patient had progressive leg weakness and paresthesia that started shortly after receiving the first vaccine dose, which lasted for several weeks. Several days following administration of the second vaccine dose, the patient was admitted to the hospital. The clinical picture and electrodiagnostic evidence were suggestive of sensorimotor demyelinating polyneuropathy. The patient was treated with plasmapheresis in the hospital and, by the day of discharge, had a significant improvement in her lower limb weakness and only minor proximal weakness without any sensory disturbance.

Discussion

To our knowledge, this is the first study assessing safety of messenger RNA COVID-19 vaccine in previously diagnosed cases of GBS. In this cohort study, which included 702 patients, only 1 needed short medical care for relapse of previous syndrome, which represents a minimal risk.

The study has limitations. First, it relies on medical records and diagnosis. However, a meticulous medical record inspection was conducted to validate all cases. Second, this study included only hospital visits, which may underestimate other symptoms that presented only in the community. Nevertheless, any significant serious neurologic concern would probably have been evaluated in a hospital setting.

The Israeli Ministry of Health and national immunization guidelines did not include a history of GBS as a precaution or contraindication to receiving the COVID-19 vaccine, and our study supports this approach.

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Accepted for Publication: August 5, 2021.

Published Online: September 1, 2021. doi:10.1001/jamaneurol.2021.3287

Corresponding Author: Shirley Shapiro Ben David, MD, Maccabi Healthcare Services, Hamered 27, Tel Aviv 6812509, Israel (shirley.shap@gmail.com).

Author Contributions: Dr Shapiro Ben David 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: Shapiro Ben David.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: Rahamim-Cohen.

Supervision: Rahamim-Cohen.

Conflict of Interest Disclosures: None reported.