Conclusion
Natural infections with varicella, tetanus and diphtheria have each been associated with facial nerve palsy. Thus, varicella, tetanus and diphtheria vaccines prevent facial nerve palsy by protecting against these natural infections. Vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause facial nerve palsy.
Epidemiological Evidence
The only vaccine ever confirmed to cause facial nerve palsy was Berna Biotech’s Nasalflu®, an inactivated intranasal influenza vaccine adjuvanted with E. coli heat-labile toxin which is no longer being produced. This vaccine was licensed for the 2000-2001 flu season in Switzerland and then permanently withdrawn from the market upon detection of the facial nerve palsy caused by the vaccine 1. It was never used in the United States.
The 2012 report by the Institute of Medicine (IOM) 2, now called the National Academy of Medicine (NAM), described two studies with sufficient validity and precision that both reported no association between inactivated influenza vaccine and facial nerve palsy 3,4. The report also described one study assessing an association between acellular pertussis vaccination and facial nerve palsy 5; however, this study did not provide convincing evidence due to a lack of validity and precision 2. Most studies published since the 2012 IOM report have also reported no association between vaccination and facial nerve palsy 6-8; however, a 2017 self-controlled case-series analysis of a California cohort did find a temporal association between receipt of meningococcal conjugate vaccine concomitantly with other vaccines and facial nerve palsy 9. A 2017 South Korean nationwide cohort study found no associations between HPV vaccination and 33 predefined serious adverse events (including facial nerve palsy) 10. A 2020 systematic review and meta-analysis found no association between HPV vaccines and many autoimmune or other rare diseases (including facial nerve palsy) 11.
Analyses of safety surveillance data from the Vaccine Safety Datalink found no significant associations between mRNA COVID-19 vaccines and 23 serious health outcomes (including facial nerve palsy) 12. Two Israeli studies found no association between Comirnaty, the Pfizer-BioNTech COVID-19 vaccine, and facial nerve palsy 13,14. A Hong Kong case-control study found an increased risk of facial nerve palsy after vaccination with CoronaVac, an inactivated COVID-19 vaccine not used in the US (aOR: 2.4; 95% CI: 1.4-4.0), but found no significant association with Comirnaty (aOR: 1.8; 95% CI: 0.9-3.5) 15. A self-controlled case series using a national English database found an increased risk of facial nerve palsy 15-21 days after vaccination with ChAdOx1nCoV-19, a viral vector COVID-19 vaccine not used in the US (IRR: 1.29; 95% CI: 1.08-1.56), but found no significant association with Comirnaty 16.
Proposed Biological Mechanism
Known causes of facial nerve palsy include infections due to Borrelia burgdorferi, the agent of Lyme disease, and zoster virus in Ramsay-Hunt syndrome. Infections with Clostridium tetani or Corynebacterium diphtheria have been associated with facial nerve palsy as well, albeit very rarely 2. Although other viral infections such as herpes simplex virus (HSV) and varicella zoster virus (VZV) have also been associated with facial nerve palsy 17-20, the pathogenesis of facial nerve palsy remains poorly understood. Hypotheses include reactivation of latent viral infections in facial nerve ganglia 21 or an autoimmune mechanism possibly with segmental demyelination 22. Regarding the association of facial nerve palsy with Nasalflu®, an influenza vaccine adjuvanted with E. coli heat-labile toxin, the most likely hypothesis is that the E. coli enterotoxin resulted in inflammation and entrapment of the facial nerve in the facial canal 23,24.
The IOM concluded that the only mechanistic evidence for an association between facial nerve palsy and tetanus or diphtheria vaccines was knowledge about the natural infection, and that there was no mechanistic evidence for hepatitis A, hepatitis B and influenza vaccines causing facial nerve palsy 2.
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.
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