Safety Signal Generation for Sudden Sensorineural Hearing Loss Following Messenger RNA COVID-19 Vaccination: Postmarketing Surveillance Using the French Pharmacovigilance Spontaneous Reporting Database

Abstract

The World Health Organization lately described sudden sensorineural hearing loss (SSNHL) as a possible adverse effect of COVID-19 vaccines. Recent discordant pharmacoepidemiologic studies invite robust clinical investigations of SSNHL after COVID mRNA vaccines. This post-marketing surveillance study, overseen by French public health authorities, is the first to clinically document post-vaccination SSNHL in terms of severity, duration, positive rechallenge cases and to examine the role of potential risk factors. This nationwide study aimed to assess the relationship between SSNHL and exposure to mRNA COVID-19 vaccines and to estimate the reporting rates (Rr) of SSNHL after mRNA vaccination per 1,000,000 doses (primary outcome). We performed a retrospective review of all suspected cases of SSNHL after mRNA COVID-19 vaccination spontaneously reported in France between January 2021 and February 2022, based on a comprehensive medical evaluation including patient medical history, side and range of hearing loss, hearing recovery outcomes after a minimum period of 3 months. Quantification of hearing loss and assessment of hearing recovery outcomes were performed according to a grading system modified from Siegel's criteria. A cutoff value of 21 days was used for the delay onset of SSNHL. The primary outcome was estimated using as a denominator the total number of doses of each vaccine administered over the study period in France. From an initial number of 400 extracted cases for both mRNA vaccines, 345 spontaneous reports were selected for further analysis. After detailed review of complementary medical data, 171 fully documented cases of SSNHL were found. Of these, 142 SSNHL cases occurred after tozinameran vaccination, with the following characteristics: Rr=1.45/1,000,000 injections; no difference between the first, second, and booster injection; complete recovery for 32 cases; median delay onset before day 21 = 4 days; median (range) age=51 (13-83) years; no sex effect. A total of 29 SSNHL cases were identified after elasomeran vaccination, with the following characteristics: Rr=1.67/1,000,000 injections; rank effect in favour of the first injection (p=0.036); complete recovery for 7 cases; median delay onset before day 21 = 8 days; median (range) age=47 (33-81) years; no sex effect. Autoimmune, cardiovascular, or audiovestibular risk factors were present in nearly 30% of cases. SSNHL was more often unilateral than bilateral for both mRNA vaccines (p<0.001 for tozinameran; p<0.003 for elasomeran), and the hearing loss degree was slight to moderately severe (Siegel's grade 1 to 3) on 74% of audiogram tests. There was 23 (13%) of profound hearing loss (Siegel's grade 5), among which 17 (74%) did not recover a serviceable ear. A positive rechallenge was documented for 8 cases, reinforcing the hypothesis of a causal relationship between mRNA COVID-19 vaccination and the occurrence of SSNHL. Episodes of SSNHL after COVID-19 mRNA vaccines are very rare adverse events that do not call into question the benefits of mRNA vaccines but deserve to be known given the potentially disabling impact of sudden deafness. It is, therefore, essential to properly characterize any post-injection SSNHL, especially in the case of a positive rechallenge, to provide appropriate individualized recommendations.