Abstract
This study establishes rates of Guillain-Barré syndrome relapse among Pfizer-BioNTech BNT162b2 vaccine receivers.
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.3,4,5 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.
Table. Patients Who Have Been Previously Diagnosed With GBS and Hospital Visits Following COVID-19 Vaccine Administrationa.
| Case No./Sex/Age, y | Time from diagnosis to first vaccination, y | Hospital visits after 1st/2nd vaccination | Time from vaccination to hospital visit, d | Emergency department (1)/hospital admission (2) | Reason for hospital visit |
|---|---|---|---|---|---|
| 1/M/80s | 6 | 1st | 0 | 1 | Paresthesia |
| 2/F/50s | 14 | 1st | 1 | 1 | Paresthesia |
| 3/F/50s | 21 | 1st | 2 | 1 | Seizure |
| 4/M/70s | 17 | 1st | 4 | 2 | SOL lung |
| 5/M/60s | 3 | 1st | 7 | 2 | Diverticulitis |
| 6/M/50s | 15 | 1st | 8 | 2 | STEMI |
| 7/M/60s | 8 | 1st | 8 | 2 | Severe COVID-19 |
| 8/F/80s | 21 | 1st | 11 | 2 | Severe COVID-19 |
| 9/F/60s | 13 | 1st | 15 | 1 | Trauma |
| 10/M/30s | 4 | 1st | 16 | 1 | Tremor |
| 11/F/30s | 11 | 1st | 16 | 2 | Delivery |
| 12/F/30s | 8 | 1st | 19 | 2 | Surgery |
| 13/M/60s | 14 | 2nd | 0 | 2 | Surgery |
| 14/M/70s | 17 | 1st | 23 | 1 | Trauma |
| 15/F/30s | 2 | 2nd | 3 | 2 | GBS |
| 16/F/50s | 2 | 2nd | 3 | 1 | Vitreous detachment |
| 17/M/70s | 12 | 2nd | 4 | 1 | Epigastric distress |
| 18/F/50s | 6 | 2nd | 5 | 1 | Hypertension |
| 19/F/40s | 21 | 2nd | 13 | 2 | Fatigue |
| 20/M/mid-teens | 12 | 2nd | 13 | 1 | Lymphadenitis |
| 21/M/60s | 8 | 2nd | 14 | 2 | Surgery |
| 22/F/50s | 4 | 2nd | 15 | 1 | Trauma |
| 23/F/60s | 2 | 2nd | 18 | 2 | Surgery |
| 24/M/40s | 7 | 2nd | 28 | 1 | Chest pain |
| 25/M/70s | 16 | 2nd | 28 | 2 | Surgery |
| 26/M/70s | 17 | 2nd | 29 | 1 | Urinary retention |
| 27/M/60s | 7 | 2nd | 30 | 2 | Surgery |
| 28/F/70s | 1 | 2nd | 31 | 1 | Hypertension |
| 29/M/60s | 2 | 2nd | 32 | 2 | COPD exacerbation |
| 30/M/70s | 20 | 2nd | 33 | 1 | Suicide attempt |
| 31/M/30s | 5 | 2nd | 33 | 1 | Trauma |
| 32/M/80s | 8 | 2nd | 34 | 2 | Surgery |
| 33/F/50s | 14 | 2nd | 37 | 1 | Hemolytic anemia |
| 34/M/60s | 11 | 1st | 60 | 1 | Vomiting |
| 35/M/60s | 3 | 2nd | 41 | 2 | Upper GI tract bleeding |
| 36/F/80s | 15 | 2nd | 49 | 1 | Syncope |
| 37/M/20s | 7 | 2nd | 53 | 1 | Trauma |
| 38/M/80s | 8 | 2nd | 56 | 2 | Pneumonia |
| 39/M/60s | 12 | 2nd | 57 | 2 | Surgery |
| 40/M/80s | 1 | 2nd | 57 | 1 | Atrial fibrillation |
| 41/M/70s | 19 | 2nd | 71 | 2 | Pericarditis |
| 42/F/60s | 5 | 2nd | 75 | 2 | Trauma |
| 43/M/70s | 1 | 2nd | 77 | 2 | Surgery |
| 44/F/70s | 6 | 2nd | 78 | 1 | Cellulitis |
| 45/F/60s | 7 | 2nd | 81 | 1 | Trauma |
| 46/M/50s | 10 | 2nd | 86 | 2 | Surgery |
| 47/M/70s | 3 | 2nd | 94 | 2 | Trauma |
| 48/M/60s | 2 | 2nd | 101 | 1 | Trauma |
Abbreviations: COPD, chronic obstructive lung disease; GI, gastrointestinal; GBS, Guillain-Barré syndrome; SOL, space-occupying lesion; STEMI, ST elevation myocardial infarction.
BNT162b2 (Pfizer-BioNTech) vaccine.
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.
References:
- 1.Israeli Ministry of Health . Coronavirus (COVID-19) vaccines. Accessed April 30, 2021. https://www.health.gov.il/UnitsOffice/HD/PH/epidemiology/td/docs/365_Corona.pdff.
- 2.Centers for Disease Control and Prevention. COVID-19 vaccines for people with underlying medical conditions. Accessed April 27, 2021. https://www.cdc.gov/coronavirus/2019-ancov/vaccines/recommendations/underlying-conditions.html.
- 3.Vellozzi C, Iqbal S, Broder K. Guillain-Barre syndrome, influenza, and influenza vaccination: the epidemiologic evidence. Clin Infect Dis. 2014;58(8):1149-1155. doi: 10.1093/cid/ciu005 [DOI] [PubMed] [Google Scholar]
- 4.Martín Arias LH, Sanz R, Sáinz M, Treceño C, Carvajal A. Guillain-Barré syndrome and influenza vaccines: a meta-analysis. Vaccine. 2015;33(31):3773-3778. doi: 10.1016/j.vaccine.2015.05.013 [DOI] [PubMed] [Google Scholar]
- 5.Lunn MP, Cornblath DR, Jacobs BC, et al. COVID-19 vaccine and Guillain-Barré syndrome: let’s not leap to associations. Brain. 2021;144(2):357-360. doi: 10.1093/brain/awaa444 [DOI] [PMC free article] [PubMed] [Google Scholar]