Research JAMA Otolaryngology–Head & Neck Surgery | Original Investigation Association of COVID-19 Vaccination and Facial Nerve Palsy A Case-Control Study Asaf Shemer, MD; Eran Pras, MD; Adi Einan-Lifshitz, MD; Biana Dubinsky-Pertzov, MD, MPH; Idan Hecht, MD Invited Commentary page 743 Related article page 767 IMPORTANCE Peripheral facial nerve (Bell) palsy has been reported and widely suggested as a possible adverse effect of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. Israel is currently the leading country in vaccination rates per capita, exclusively using the BNT162b2 vaccine, and all residents of Israel are obligatory members of a national digital health registry system. These factors enable early analysis of adverse events. OBJECTIVE To examine whether the BNT162b2 vaccine is associated with an increased risk of acute-onset peripheral facial nerve palsy. DESIGN, SETTING, AND PARTICIPANTS This case-control study was performed from January 1 to February 28, 2021, at the emergency department of a tertiary referral center in central Israel. Patients admitted for facial nerve palsy were matched by age, sex, and date of admission with control patients admitted for other reasons. EXPOSURES Recent vaccination with the BNT162b2 vaccine. MAIN OUTCOMES AND MEASURES Adjusted odds ratio for recent exposure to the BNT162b2 vaccine among patients with acute-onset peripheral facial nerve palsy. The proportion of patients with Bell palsy exposed to the BNT162b2 vaccine was compared between groups, and raw and adjusted odds ratios for exposure to the vaccine were calculated. A secondary comparison with the overall number of patients with facial nerve palsy in preceding years was performed. RESULTS Thirty-seven patients were admitted for facial nerve palsy during the study period, 22 (59.5%) of whom were male, and their mean (SD) age was 50.9 (20.2) years. Among recently vaccinated patients (21 [56.7%]), the mean (SD) time from vaccination to occurrence of palsy was 9.3 (4.2 [range, 3-14]) days from the first dose and 14.0 (12.6 [range, 1-23]) days from the second dose. Among 74 matched controls (2:1 ratio) with identical age, sex, and admittance date, a similar proportion were vaccinated recently (44 [59.5%]). The adjusted odds ratio for exposure was 0.84 (95% CI, 0.37-1.90; P = .67). Furthermore, analysis of the number of admissions for facial nerve palsy during the same period in preceding years (2015-2020) revealed a relatively stable trend (mean [SD], 26.8 [5.8]; median, 27.5 [range, 17-35]). CONCLUSIONS AND RELEVANCE In this case-control analysis, no association was found between recent vaccination with the BNT162b2 vaccine and risk of facial nerve palsy. Author Affiliations: Department of Ophthalmology, Shamir Medical Center, Be’er Ya’akov, Israel (Shemer, Pras, Einan-Lifshitz, Dubinsky-Pertzov, Hecht); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Shemer, Pras, Einan-Lifshitz, Dubinsky-Pertzov, Hecht); The Matlow’s Ophthalmo-Genetics Laboratory, Department of Ophthalmology, Shamir Medical Center, Be’er Ya’akov, Israel (Pras). Corresponding Author: Asaf Shemer, MD, Department of Ophthalmology, Shamir Medical Center, Be’er Ya’akov, Tzrifin 70300, Israel (shemerasafmd@gmail.com). JAMA Otolaryngol Head Neck Surg. 2021;147(8):739-743. doi:10.1001/jamaoto.2021.1259 Published online June 24, 2021. © 2021 American Medical Association. All rights reserved. (Reprinted) 739 Downloaded From: https://jamanetwork.com/ on 10/05/2022 Research Original Investigation Association of COVID-19 Vaccination and Facial Nerve Palsy C OVID-19 is caused by SARS-CoV-2, and immunity can be achieved either by native or preventive immuniza- tion of the population. Thus far, the US Food and Drug Administration has issued an emergency use authorization for 3 novel COVID-19 vaccines.1 On December 11, 2020, the BNT162b2 (Pfizer-BioNTech) vaccine was the first to achieve this authorization, and millions of people worldwide have been vaccinated with it.2 Peripheral facial nerve palsy has been reported and widely suggested as a possible adverse effect of the BNT162b2 vaccine.3-9 This was initially prompted by the imbalance in pe- ripheral facial nerve palsy cases reported in the original effi- cacy trial published in December 2019.10,11 Peripheral facial nerve palsy was reported in 4 cases among the vaccinated par- ticipants and none of the controls.10,11 Since then, several case reports and commentaries4-9 and much media attention have been devoted to the subject,3,5,6,12,13 yet robust evidence is scarce. On December 19, 2020, Israel launched a national vacci- nation program. Israel is the leading country in vaccination rates per capita, with approximately 92% and 85% of the popu- lation older than 50 years immunized with the first and sec- ond doses, respectively, as of March 1, 2021.14 At present, vac- cination in Israel is promoted exclusively with the BNT162b2 vaccine. All residents of Israel are members of a national digi- tal health registry system. These factors provide a unique op- portunity to perform an early real-world analysis of adverse events due to the BNT162b2 vaccine and report on an asso- ciation or the lack thereof regarding peripheral facial nerve palsy after vaccination. Methods This study adhered to the tenets of the Declaration of Helsinki15 and was approved by the institutional review board of the Shamir Medical Center. Owing to its retrospective nature, a waiver of informed consent was granted. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Design and Patient Population The BNT162b2 vaccine was given emergency use authoriza- tion by the US Food and Drug Administration in early Decem- ber 2020. It has been authorized for all individuals older than 16 years and is injected in 2 doses separated by a 21-day interval. We conducted a case-control study examining the asso- ciation between exposure to the BNT162b2 vaccine and facial nerve palsy. Cases were defined as patients who were admit- ted to the emergency department of a single tertiary referral center in Israel (Shamir Medical Center [formerly Assaf Harofeh], Tzrifin) and were diagnosed with new-onset periph- eral facial nerve palsy from January 1 to February 28, 2021. In Israel, it is standard practice to refer all patients with new- onset peripheral nerve palsy for evaluation in the emergency department. Data were collected by a computerized hospital system according to International Classification of Diseases, Key Points Question Is the Pfizer-BioNTech BNT162b2 COVID-19 vaccine associated with increased risk of peripheral facial nerve palsy? Findings In this case-control study of 37 patients with acute-onset facial nerve palsy and a matched control group, no increased risk of facial nerve palsy was observed after vaccination. In addition, no meaningful increase in the number of admissions for facial nerve palsy was observed compared with preceding years. Meaning These outcomes suggest that recent vaccination with the BNT162b2 vaccine is not associated with an increased risk of facial nerve palsy. Ninth Revision, code 351.0 (Bell palsy). We retrospectively re- viewed each medical record and manually recorded rates and timing of vaccination with the BNT162b2 vaccine. Included were all patients who were older than 18 years and of any medi- cal status. Controls were patients who had been admitted to the same emergency department for any reason other than facial nerve palsy and were matched for age, sex, and admis- sion date within 48 hours. Controls were matched for date of admission for 2 rea- sons. First, seasonality was found to be a risk factor for pe- ripheral nerve palsy, and matching enabled us to exclude this as a possible bias between groups. Second, vaccines were being rolled out in Israel during this time, and later admission pre- disposed a given patient to a higher chance of being vacci- nated. Matching for admission date was a way to ensure that timing was not a possible factor for bias. Two controls were matched for each case and were ran- domly selected. In both groups, the percentage of patients ex- posed to the BNT162b2 vaccine (first or second dose) within the previous 30 days was calculated and the adjusted and un- adjusted odds ratios (ORs) for exposure were compared with corresponding 95% CIs. Age, sex, and seasonality are risk fac- tors for facial nerve palsy and are inherently controlled for by the study design; however, existence of immune- or inflam- matory-related disorders, diabetes, and a previous episode of peripheral nerve palsy are also implicated as possible risk fac- tors. These factors were extracted, and an adjusted OR con- trolling for these factors was also calculated. As a secondary analysis, all cases of facial nerve palsy dur- ing the same period (January to February) in the 6 preceding years were extracted according to International Classification of Diseases, Ninth Revision, codes and compared with 2021. The months of January and February were selected because the na- tional vaccination campaign in Israel began on December 19, 2020, and by March 1, 2021, more than 92% of the population older than 50 years was already vaccinated with the first dose.14 Thus, early postvaccination adverse events should be evi- dent during this period. For this analysis, the data are pre- sented as they are and the overall trend is presented without statistical analyses. Statistical Analysis Statistical analysis was performed using IBM SPSS Statistics, version 25 (IBM Corp). Categorical variables such as sex and 740 JAMA Otolaryngology–Head & Neck Surgery August 2021 Volume 147, Number 8 (Reprinted) jamaotolaryngology.com © 2021 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/05/2022 Association of COVID-19 Vaccination and Facial Nerve Palsy Original Investigation Research Table 1. Characteristics of Patients With New-Onset Peripheral Facial Nerve Palsy After Recent Vaccination With the BNT162b2 (Pfizer-BioNTech) Vaccine Patient No. Comorbidities Laterality Status at last follow-up HB gradea IV Partially recovered Partially recovered 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 None None Dyslipidemia Hypertension Hypertension, prostate cancer None Cardiac pacemaker Dyslipidemia None None Hepatitis C Asthma None None Diabetes None None Small fiber neuropathy Hypertension, OSA, cochlear Ménière disease Left Dyslipidemia, hypothyroidism, thalassemia Hypertension, BPH, diabetes Right Right Left Left Left Right Left Right Right Right Right Right Right Right Right Left Right Right Left Left NA IV IV NA NA VI IV III III NA NA III NA NA II III IV III III NA NA NA NA NA NA NA NA NA NA NA NA NA Partially recovered Partially recovered Partially recovered Partially recovered Partially recovered Partially recovered Partially recovered Abbreviations: BPH, benign prostatic hyperplasia; HB, House-Brackmann; NA, not available; OSA, obstructive sleep apnea. a Obtained at admission. Scores range from I to VI, with higher scores indicating severe nerve damage. existence of diabetes were compared using the χ2 test. Con- tinuous variable distributions were tested for normality by the Shapiro-Wilk test. Independent 2-tailed t tests were con- ducted for continuous variables with a normal distribution and the Mann-Whitney test for continuous variables with a non- normal distribution. The OR for exposure to the vaccine was calculated with the corresponding 95% CI. Two-sided P < .05 was considered statistically significant. For sample calcula- tion, a case-control model was used with a CI of 0.95 and power was set at 80%. Assuming an exposed proportion of 0.6 among the controls and an expected OR of 4.00, the total sample size needed (in both groups) to detect a significant association was calculated to be 88 patients. Sample size calculations were performed using MedCalc software, version 17 (MedCalc Software Ltd). Results During the study period, a total of 37 patients were admitted for an acute-onset facial nerve palsy. The mean (SD) patient age was 50.9 (20.2) years; 22 (59.5%) were male and 15 (40.5%) were female. Most of the patients were discharged on the same day, and only 2 were admitted for further evaluation. Of the 37 patients, 4 (10.8%) had diabetes, 2 (5.4%) had immune- or inflammatory-associated disorders (familial Mediterranean fe- ver and psoriasis), and 2 (5.4%) had a previous episode of pe- ripheral facial nerve palsy. A detailed description of the cases is provided in Table 1. Comparing recently vaccinated (21 of 37 [56.7%]) with unvaccinated (16 of 37 [43.2%]) patients showed no meaningful difference in age (mean [SD], 55.5 [19.2] vs 44.9 [20.5] years; P = .12) or sex (13 [61.9%] male vs 9 [56.3%] male; P = .73). Among recently vaccinated patients who re- ceived only the first dose, the mean (SD) time from vaccina- tion to occurrence of facial nerve palsy was 9.3 (4.2 [range, 3-14]) days; among those who completed the vaccination pro- cess with the second dose (10 of 37 [27.0%]), the mean (SD) time from vaccination was 14.0 (12.6 [range, 1-23]) days. For each patient admitted with a case of new-onset pe- ripheral facial nerve palsy, 2 matched controls were ran- domly selected. No meaningful differences were seen be- tween the controls and cases in terms of a diagnosis of diabetes (4 of 37 [10.8%] among cases vs 15 of 74 [20.3%] among con- trols; difference, 9.5% [95% CI, −6.4% to 21.8%]), rates of im- mune- or inflammatory-related disorders (2 of 37 [5.4%] among cases vs 3 of 74 [4.1%] among controls; difference, 1.3% [95% CI, −6.8% to 13.9%]), and a previous episode of peripheral nerve palsy (2 of 37 [5.4%] among cases vs 0 of 74 among controls; difference, 5.4% [95% CI, −0.9% to 17.7%]). Overall, 21 of 37 individuals (56.8%) with facial nerve palsy were recently vac- cinated with the first or second dose of the BNT162b2 vac- cine, compared with 44 of 74 (59.5%) in the control group (Table 2). The unadjusted OR for exposure to the vaccine among cases was 0.90 (95% CI, 0.40-1.99; P = .79). After adjusting for existence of immune- or inflammatory- related disorders, diabetes, and a previous episode of periph- eral nerve palsy, the OR for exposure to the vaccine among cases was 0.84 (95% CI, 0.37-1.90; P = .67). In addition, we com- pared the overall number of patients with acute-onset facial nerve palsy with that of preceding years, before the advent of the COVID-19 pandemic or vaccine. Table 3 shows the num- ber of cases of facial nerve palsy admitted during January and jamaotolaryngology.com (Reprinted) JAMA Otolaryngology–Head & Neck Surgery August 2021 Volume 147, Number 8 741 © 2021 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/05/2022 Research Original Investigation Association of COVID-19 Vaccination and Facial Nerve Palsy Table 2. Distribution of Vaccinated and Nonvaccinated Patients Among Cases With New-Onset Peripheral Facial Nerve Palsy and Matched Controls Patient group Vaccinated Nonvaccinated Total No. of cases No. of controls Total No. 21 16 37 44 30 74 65 46 111 Table 3. Facial Nerve Palsy Cases in January and February 2021 and During the Same Period in the 6 Preceding Years No. of cases Age, mean (SD), y Male, No. (%) Year 2015 2016 2017 2018 2019 2020 2021 28 26 28 17 27 35 37 49.5 (17.8) 51.4 (17.7) 50.2 (20.8) 52.3 (21.9) 48.5 (21.0) 49.2 (19.4) 50.9 (20.2) 17 (60.7) 17 (65.4) 17 (60.7) 12 (70.6) 15 (55.6) 23 (65.7) 22 (59.5) February of 2021 and in the same period during the 5 preced- ing years. A similar volume of admissions was seen in 2021 for facial nerve palsy compared with preceding years (mean [SD], 26.8 [5.8] cases; median, 27.5 [range, 17-35] cases). Discussion In this study, occurrence of acute-onset facial nerve palsy was evaluated for an association with recent SARS-CoV-2 vaccina- tion with the BNT162b2 vaccine. In a case-control compari- son with controls matched for age, sex, and date of admis- sion, no association between facial nerve palsy and vaccination status was observed. In addition, when comparing the num- ber of patients admitted for facial nerve palsy during the same period in preceding years, a similar volume of admissions is seen. These results are noteworthy given that the first vacci- nation occurred in Israel on December 19, 2020, and by March 1, 2021, more than 92% of the population of Israel older than 50 years was already vaccinated with the first dose.14 Given even a small association of the vaccine with facial nerve palsy, a dramatic increase in cases should have been evident. In the original BNT162b2 safety and efficacy trial pub- lished in December of 2020,10,11 peripheral facial nerve palsy was reported in 4 cases among the vaccinated participants and none of the controls. Similar results were published later with regard to the messenger RNA (mRNA–1273 [Moderna] SARS-CoV-2 vaccine.10 The authors reported 3 participants who developed Bell palsy in the vaccine group, compared with only 1 participant in the placebo group during the obser- vation period of the trial (>28 days after injection).10 This seemingly small detail sparked considerable attention. Several opinion articles and case reports4,7-9 have been published on the subject, and media attention has been extensive.3,5,6,12,13 This attention could influence vaccination rates in addition to the effort of global public health in elimi- nating infection rates. Previously, facial nerve palsy has been reported as a pos- sible adverse event in other vaccinations, including influ- enza vaccine and meningococcal conjugate vaccine.9,16 The mechanism for this is thought to involve the additive adju- vants that initiate an immunomodulatory response within the cells.17 However, the mRNA-based vaccines produced by Pfizer- BioNTech and Moderna use a different mechanism without ad- juvants. An immune response is nonetheless a necessary com- ponent for efficacy and, via either mimicry of host molecules or bystander activation of dormant autoreactive T cells, a theoretical association with facial nerve palsy could occur.18 Another possibility is that the BNT162b2 vaccine might in- duce innate immune activation and production of interferon proteins by a combined effect of mRNA and lipids.9 Facial nerve palsy has been reported as a possible rare complication of interferon therapy.19 Limitations This study has several limitations. First, only the effects of re- cent vaccination were evaluated, and long-term outcomes are currently unavailable for analysis. Second, we examined only facial nerve palsy as an outcome. Third, all patients received the BNT162b2 vaccine, and results cannot be generalized to other SARS-CoV-2 vaccine types. Finally, the secondary analy- sis of overall patients admitted compared with preceding years could be biased by unmeasurable factors such as referral patterns. Conclusions In this case-control study, no association between acute facial nerve palsy and recent vaccination with the BNT162b2 vaccine was observed. In addition, despite rapid and exten- sive vaccination of the population, a similar volume of admis- sions for facial nerve palsy was seen compared with the same period in preceding years. ARTICLE INFORMATION Accepted for Publication: May 6, 2021. Published Online: June 24, 2021. doi:10.1001/jamaoto.2021.1259 Author Contributions: Drs Shemer and Hecht had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Shemer, Pras, Hecht. Acquisition, analysis, or interpretation of data: Shemer, Einan-Lifshitz, Dubinsky-Pertzov, Hecht. Drafting of the manuscript: Shemer, Pras, Dubinsky-Pertzov. Critical revision of the manuscript for important intellectual content: Shemer, Einan-Lifshitz, Hecht. Statistical analysis: Hecht. Administrative, technical, or material support: Shemer, Dubinsky-Pertzov, Hecht. Supervision: Shemer, Pras, Einan-Lifshitz, Hecht. Conflict of Interest Disclosures: None reported. REFERENCES 1. US Food and Drug Administration. COVID-19 vaccines. Updated May 11, 2021. Accessed March 10, 2021. https://www.fda.gov/emergency- preparedness-and-response/coronavirus-disease- 2019-covid-19/covid-19-vaccines 2. US Food and Drug Administration. Pfizer-BioNTech COVID-19 vaccine. Updated May 11, 2021. Accessed January 30, 2021. https://www.fda. gov/emergency-preparedness-and-response/ 742 JAMA Otolaryngology–Head & Neck Surgery August 2021 Volume 147, Number 8 (Reprinted) jamaotolaryngology.com © 2021 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/05/2022 Association of COVID-19 Vaccination and Facial Nerve Palsy Original Investigation Research coronavirus-disease-2019-covid-19/pfizer- biontech-covid-19-vaccine online February 21, 2021. doi:10.1007/s00415-021- 10462-4 Accessed March 1, 2021. https://datadashboard. health.gov.il/COVID-19/general 3. Awasthi P. COVID-19 vaccine: 13 out of nearly 2 mil Israelis suffer facial paralysis. January 15, 2021. Accessed January 30, 2021. https://www.jpost. com/health-science/13-people-suffered-face- paralysis-after-corona-vaccine-655542 4. Repajic M, Lai XL, Xu P, Liu A. Bell’s palsy after second dose of Pfizer COVID-19 vaccination in a patient with history of recurrent Bell’s palsy. Brain Behav Immun Health. 2021;13:100217. doi:10.1016/ j.bbih.2021.100217 5. Shapiro N. Can getting the coronavirus vaccine lead to Bell’s palsy? December 16, 2020. Accessed March 21, 2021. https://www.forbes.com/sites/ ninashapiro/2020/12/16/can-getting-the- coronavirus-vaccine-lead-to-bells-palsy/ 6. Buntz B. Is there a link between Bell’s palsy and COVID-19 vaccines? March 2, 2021. Accessed March 21, 2021. https://www.massdevice.com/is-there-a- link-between-bells-palsy-and-covid-19-vaccines/ 7. Shemer A, Pras E, Hecht I. Peripheral facial nerve palsy following BNT162b2 (COVID-19) vaccination. Isr Med Assoc J. 2021;23(3):143-144. 8. Colella G, Orlandi M, Cirillo N. Bell’s palsy following COVID-19 vaccination. J Neurol. Published 9. Ozonoff A, Nanishi E, Levy O. Bell’s palsy and SARS-CoV-2 vaccines. Lancet Infect Dis. 2021;21(4): 450-452. doi:10.1016/S1473-3099(21)00076-1 10. Polack FP, Thomas SJ, Kitchin N, et al; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/ NEJMoa2034577 11. Shimabukuro T. COVID-19 vaccine safety update, Advisory Committee on Immunization Practices (ACIP) meeting. January 27, 2021. Accessed January 30, 2021. https://www.cdc.gov/ vaccines/acip/meetings/downloads/slides-2021- 01/06-COVID-Shimabukuro.pdf 12. Drumm C. Can the COVID-19 vaccine cause Bell’s palsy? experts say no. January 25, 2021. Accessed March 21, 2021. https://thehealthnexus. org/can-the-covid-19-vaccine-cause-bells-palsy- experts-say-no/ 13. Facial Palsy UK. Facial palsy and COVID-19 vaccine. Updated March 26, 2021. Accessed February 21. 2021. https://www.facialpalsy.org.uk/ news/facial-palsy-and-covid-19-vaccine/ 14. Israel Ministry of Health. Corona virus in Israel–general situation. Updated May 13, 2021. Invited Commentary Bell Palsy and COVID-19 Overcoming the Fear of “Known Unknowns” C. W. David Chang, MD 15. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053 16. Zhou W, Pool V, DeStefano F, et al.; VAERS Working Group. A potential signal of Bell’s palsy after parenteral inactivated influenza vaccines: reports to the Vaccine Adverse Event Reporting System (VAERS)—United States, 1991-2001. Pharmacoepidemiol Drug Saf. 2004;13(8):505-510. doi:10.1002/pds.998 17. Mutsch M, Zhou W, Rhodes P, et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. N Engl J Med. 2004; 350(9):896-903. doi:10.1056/NEJMoa030595 18. Principi N, Esposito S. Do vaccines have a role as a cause of autoimmune neurological syndromes? Front Public Health. 2020;8(8):361. doi:10.3389/ fpubh.2020.00361 19. Hwang I, Calvit TB, Cash BD, Holtzmuller KC. Bell’s palsy: a rare complication of interferon therapy for hepatitis C. Dig Dis Sci. 2004;49(4):619- 620. doi:10.1023/b:ddas.0000026389.56819.0c Related articles pages 739 and 767 The emergency use authorization of the first 2 messenger RNA COVID-19 vaccines in the US has given rise to a fascinating study of otolaryngological medical and social influence issues. As of May 1, 2020, the COVID-19 pandemic has resulted in more than 151 million cases and 3.2 mil- lion deaths worldwide. In the US, these statistics include 32.4 million cases (9757 per 100 000 population) and 576 000 deaths (173 per 100 000 population).1 The cold ste- rility of numbers is difficult to put into context. Likewise, when Pfizer-BioNTech and Moderna revealed cases of Bell palsy in their vaccine trials, concerns grew regarding the potential of the vaccines to cause Bell palsy. Numbers thrown out to either demonstrate or refute safety are likewise difficult for the pub- lic to contextualize. Epidemiologically, linking the vaccine with an adverse event requires accurate estimation of event inci- dence in association with the vaccine, comparison with a nonvaccinated group, and understanding of the background incidence. Historical background rates for safety surveillance pro- vide some context, but their use is not without caveats. Rates vary not only by patient factors such as age (older age associ- ated with higher incidence) and sex (mixed results), but also vary by geography, time, and collection method (traditional vs electronic medical record [EMR] review, hospital-based vs general practice–based vs “door-to-door” assessment). Although many publications cite an incidence of 11.0 to 51.9 per 100 000 person-years,2 these rates can vary widely. For example, a large study in the UK using Clinical Practice Research Datalink (one of the world’s largest longitudinal da- tabases containing EMRs from more than 640 UK general prac- tices) identified 14 460 patients with Bell palsy, an overall in- cidence of 37.7 per 100 000 person-years from 2001 to 2012. Only new cases of Bell palsy were included.2 In contrast, an Israeli study using EMR data from a health maintenance or- ganization from 2003 to 2012 identified 4463 patients with an overall incidence of 87.0 per 100 000 person-years.3 Further confounding background rates, the COVID-19 pandemic itself has been theorized to affect the incidence of Bell palsy, with mixed findings. In this issue of JAMA Otolaryngology, Tamaki et al4 que- ried a large-scale EMR database contributed to by 41 health care organizations during a 1-year span to look more specifically at rates of Bell palsy in patients with a COVID-19 diagnosis. Of 348 088 identified patients with COVID-19, 284 had a diagno- sis of Bell palsy within 8 weeks of COVID-19 diagnosis: 153 pa- tients had new-onset Bell palsy, whereas 131 had recurrent Bell palsy. The authors translate this to an 8-week incidence of 82 per 100 000 patients with COVID-19. However, if using a crude analysis and assuming a prepandemic rate of 40 per 100 000 person-years and no seasonality, Bell palsy would be ex- pected to naturally occur in only 21 of 348 088 patients during an 8-week period. This suggests that COVID-19 could jamaotolaryngology.com (Reprinted) JAMA Otolaryngology–Head & Neck Surgery August 2021 Volume 147, Number 8 743 © 2021 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/05/2022