Bell's palsy and SARS-CoV-2 vaccines—an unfolding story – Authors' reply

We thank Nicola Cirillo and Richard Doan for their careful consideration of our Comment¹ and the available safety data from the recent mRNA vaccine trials. They are correct to call attention to the follow-up period for reporting safety events as important to interpret event rates appropriately. We have three points in response.

First, data reported in the US Food and Drug Administration briefings suggest risk of Bell's palsy is greatest within 1 month of a second vaccine dose. Page 43 of the Pfizer briefing notes “from dose 1 through 1 month after dose 2, there were three reports of Bell's palsy in the vaccine group and none in the placebo group”.² According to page 42 of the Moderna briefing,³ three cases of Bell's palsy occurred 32, 28, and 27 days after vaccination (presumably first dose) versus one case that occurred 17 days after injection in the placebo group. Using an abbreviated follow-up period of 2 months after the first dose—ie, 1 month after the second dose—there are six Bell's palsy cases reported in the combined vaccine groups versus one case in the combined placebo groups, with a denominator of approximately 5664 person-years in each group. Thus we observe annualised incidence rate in the vaccine group of roughly 106 cases per 100 000 population, again 3·5–7·0 times the expected background rate of 15–30 cases per 100 000 population per year.

Second, although risk of a vaccine-associated event begins after the first dose of vaccine is received, this risk increases substantially after the second dose.2, 3 Our original calculation does not fully account for the month of observation between first and second doses, but the authors' assumption of 12 weeks observation might be overly conservative since it assumes constant risk over 3 months of follow-up. A weighting function applied to observation time would offer a more sophisticated analysis. A nuanced interpretation of these safety data must await availability of complete datasets from both trials.

Third, the greater than three-fold increase in Bell's palsy incidence observed in EudraVigilance when comparing mRNA vaccines to other vaccines adds to the evidence that mRNA vaccines impose higher risk of Bell's palsy than other vaccines based on different platforms, alongside ongoing work to identify likely mechanisms.⁴ We agree this evidence might be a consideration for clinicians when advising patients with a history of Bell's palsy on the choice of vaccine to receive.

In conclusion, we appreciate attention to these data and clarification of an important point in our original Comment. The available data remain consistent with a more than three-fold increase in risk for Bell's palsy within 1 month of a second vaccine dose.