key: cord-0768656-1fvh7o3o
authors: Shasha, David; Bareket, Ronen; Sikron, Fabienne Hershkowitz; Gertel, Omer; Tsamir, Judith; Dvir, David; Mossinson, David; Heymann, Anthony D.; Zacay, Galia
title: Real-world safety data for the Pfizer BNT162b2 SARS-CoV-2 vaccine, historical cohort study
date: 2021-09-27
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2021.09.018
sha: 7851628f3294ddc3108373dfd172e8cf7655eb2b
doc_id: 768656
cord_uid: 1fvh7o3o

OBJECTIVE: The Pfizer BNT162b2 vaccine showed a reassuring safety profile in clinical trials, but real-world data are scarce. Bell’s palsy, herpes-zoster, Guillain-Barré syndrome (GBS) and other neurological complaints in proximity to vaccination have received special public attention. We compared their rates among vaccinated and unvaccinated individuals. METHODS: Individuals ≥16 years vaccinated with at least one dose of BNT162b2 were eligible for this historical-cohort study in a health maintenance organization insuring 1.2 million citizens. Each vaccinee was matched to a non-vaccinated control by sex, age, population sector (general Jewish, Arab, ultra-orthodox Jewish) and comorbidities. Diagnosis of Covid-19 before or after vaccination was an exclusion criterion. The outcome was a diagnosis of: Bell’s palsy, GBS, herpes-zoster, or symptoms of numbness or tingling, coded in the visit diagnosis field using ICD-9 codes. Diagnoses of Bell’s palsy and GBS were verified by individual file review. RESULTS: Of 406,148 individuals vaccinated during the study period, 394,609 (97.2%) were eligible (11,539 excluded). 233,159 (59.1%) were matched with unvaccinated controls. Mean follow was 43±15.14 days. In vaccinated and unvaccinated individuals there were 23 versus 24 cases of Bell’s palsy (RR 0.96, CI 0.54-1.70), 1 versus 0 cases of GBS, 151 versus 141 cases of herpes-zoster (RR 1.07, CI 0.85-1.35), and 605 versus 497 cases of numbness or tingling (RR 1.22, CI 1.08-1.37), respectively. CONCLUSIONS: No association was found between vaccination, Bell’s palsy, herpes-zoster or GBS. Symptoms of numbness or tingling were more common among vaccinees. This study adds reassuring data regarding the safety of the BNT162b2 vaccine.

The Pfizer BNT162b2 vaccine showed a reassuring safety profile in clinical trials, but real-world 24 data are scarce. Bell's palsy, herpes-zoster, Guillain-Barré syndrome (GBS) and other 25 neurological complaints in proximity to vaccination have received special public attention. We 26 compared their rates among vaccinated and unvaccinated individuals. 27 Methods: 28 Individuals ≥16 years vaccinated with at least one dose of BNT162b2 were eligible for this 29 historical-cohort study in a health maintenance organization insuring 1.2 million citizens. Each 30 vaccinee was matched to a non-vaccinated control by sex, age, population sector (general 31 Jewish, Arab, ultra-orthodox Jewish) and comorbidities. Diagnosis of Covid-19 before or after 32 vaccination was an exclusion criterion. The outcome was a diagnosis of: Bell's palsy, GBS, 33 herpes-zoster, or symptoms of numbness or tingling, coded in the visit diagnosis field using ICD-34 9 codes. Diagnoses of Bell's palsy and GBS were verified by individual file review. 35 Results: 36 Of 406,148 individuals vaccinated during the study period, 394,609 (97.2%) were eligible 37 (11,539 excluded) . 233,159 (59.1%) were matched with unvaccinated controls. Mean follow 38 was 43±15.14 days. 39 In vaccinated and unvaccinated individuals there were 23 versus 24 cases of Bell's palsy (RR Moderna(5, 6)), herpes-zoster(7-9), and several other neurological adverse events(10, 11). Four outcomes were assessed in this study: Bell's palsy, Guillain-Barré syndrome (GBS), herpes-119 zoster, and symptoms of numbness or tingling sensation. Diagnoses were extracted using ICD-9 120 codes (supplementary Table 1 ) from the visit diagnosis field, which is mandatory in our 121 electronic medical record (EMR). The diagnosis was considered an outcome whether the 122 physician attributed it to the vaccine or not. For each outcome, individuals who had the same 123 diagnosis during 30 days before vaccination/reference day were excluded (less than 0.5%). The Table 1 . Variables used for 159 matching were well balanced between study groups. 160 Overall follow-up was 9,988,509 days for each group, with mean follow-up of 43 ± 15.14 days 161 per participant. Mean gap between doses was 22 ± 1.55 days, and mean follow-up after the 162 second dose was 32 ± 8.28 days (overall follow-up was 4,226,133 days after the second dose). In this study we sought to investigate possible associations between the BNT162b2 vaccine and 218 several medical conditions of concern. We found no association between BNT162b2 vaccination 219 and Bell's palsy, herpes-zoster or GBS. Mild, non-specific neurological complaints of numbness 220 and tingling were more frequent among vaccinees, with higher odds for females and older 221 individuals.

Bell's palsy received unusual public attention shortly after the FDA EUA of the vaccine. non-significant, NS), was higher than the reported rate in the general population. This finding 235 may be explained by the mean age of our cohort, as the incidence of Bell's palsy is higher 236 among older persons(16, 17), who were the first to get vaccinated, and were over-represented 237 in our cohort (table 1) . 238 

Concerns of association between the vaccine and zoster have been raised by clinicians(7-9) and 239 by the press. Our study found no such association. 240 As for other new vaccines, concerns regarding possible association with GBS were raised by 241 health-care providers. In a commentary, reviewing the lack of association between COVID itself 242 and GBS, as well with many other vaccines(18), the authors predicted that vaccines encoding 243 the spike protein would not confer additional risk of GBS, and stressed the need for reliable 244 data as during mass vaccination rare cases of GBS would inevitably occur by coincidence 245 following vaccination. In our cohort we found one case of confirmed GBS among vaccinated 246 individuals, and no cases among the controls. The reported annual incidence of GBS is 1.7 cases 247 per 100,000 population(18, 19), therefore our study cohort was too small for estimating the 248 incidence of GBS, or its association with the vaccine, and could not exclude an elevated risk. Outcomes of this study were identified by visit diagnoses, which might be partial or inaccurate. 283 We therefore chose to focus on few clinical outcomes of concern. Furthermore, we confirmed 284 each case of Bell's palsy and GBS by reviewing the patients' EMR to provide reliable 285 information. Inaccurate or under-reporting of visit diagnoses probably resulted in a non-286 differential misclassification. In this context it is important to emphasize that GBS is a rare 287 condition and larger cohorts are required for proper monitoring of its association with the 288 vaccine(18). The relatively short follow-up period, further limited the ability of this study to 289 assess the association of GBS with the vaccine. We included data regarding GBS in this report, 290 despite insufficient power, to support future meta-analysis. 291 In conclusion, we found no association between vaccination and Bell's palsy, GBS or zoster. As Age group* (%) 1 1 

Analysis of matched case-control studies

Efficacy and Safety of 374 the mRNA-1273 SARS-CoV-2 Vaccine. The New England journal of medicine

Bell's palsy and SARS-CoV-2 vaccines. The Lancet Infectious 377 diseases

Epidemiology of Bell's palsy in 379 an Italian Health District: incidence and case-control study

Bell's Palsy: Clinical Analysis of 372

275 (6%) 2,288 (2%) 2,288 (2%) 18-35 91

Sector* (%)

Lung disease** (%)

Oncological condition