背景:世界卫生组织最近将突发性感觉神经性听力损失(SSNHL)描述为COVID-19疫苗的可能不良反应。最近不一致的药物流行病学研究要求对COVIDmRNA疫苗后的SSNHL进行强有力的临床研究。这项上市后监测研究,在法国公共卫生当局的监督下,是第一个临床记录疫苗接种后SSNHL的严重程度,持续时间,积极的再挑战案例,并检查潜在风险因素的作用。
目的:这项全国性研究旨在评估SSNHL与mRNACOVID-19疫苗暴露之间的关系,并估计每1,000,000剂mRNA疫苗接种后SSNHL的报告率(Rr)(主要结果)。
方法:我们根据包括患者病史在内的综合医学评估,对2021年1月至2022年2月在法国自发报告的mRNACOVID-19疫苗接种后所有疑似SSNHL病例进行了回顾性审查。听力损失的侧面和范围,至少3个月后的听力恢复结果。根据Siegel标准修改的分级系统进行听力损失的量化和听力恢复结果的评估。21天的截断值用于延迟SSNHL的发作。主要结果是使用在法国研究期间施用的每种疫苗的总剂量作为分母来估计的。
结果:从两种mRNA疫苗的初始提取的400例病例中,选择345份自发报告进行进一步分析。在详细审查了补充医疗数据后,发现了171例完全记录的SSNHL病例。其中,142例SSNHL病例发生在Tozinameran疫苗接种后,具有以下特征:Rr=1.45/1,000,000次注射;第一次没有差异,第二,和加强注射;32例完全恢复;中位延迟发病前21天=4天;中位(范围)年龄=51(13-83)岁;无性别影响。共有29例SSNHL病例在接种弹性球虫疫苗后被确认,具有以下特征:Rr=1.67/1,000,000次注射;排名效应有利于首次注射(p=0.036);7例完全恢复;中位延迟发病前21天=8天;中位(范围)年龄=47(33-81)岁;无性别影响。自身免疫,心血管,近30%的病例存在前庭或听觉危险因素。对于两种mRNA疫苗,SSNHL通常是单侧的,而不是双侧的(对于Tozinameran,p<0.001;对于elastomeran,p<0.003),在74%的听力图测试中,听力损失程度为轻度至中度(Siegel的1至3级)。有23(13%)的严重听力损失(西格尔的5级),其中17人(74%)没有恢复可用的耳朵。记录了8例积极的重新挑战,加强了COVID-19mRNA疫苗接种与SSNHL发生之间因果关系的假设。
结论:COVID-19mRNA疫苗后SSNHL的发作是非常罕见的不良事件,不会质疑mRNA疫苗的益处,但鉴于突发性耳聋的潜在致残影响,值得了解。是的,因此,对于正确表征任何注射后的SSNHL至关重要,尤其是在积极挑战的情况下,提供适当的个性化建议。
BACKGROUND: The World Health Organization recently 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-19 messenger RNA (mRNA) vaccines. This
postmarketing surveillance study, overseen by French public health authorities, is the first to clinically document postvaccination SSNHL and examine the role of potential risk factors.
OBJECTIVE: This nationwide study aimed to assess the relationship between SSNHL and exposure to mRNA COVID-19 vaccines and estimate the reporting rate (Rr) of SSNHL after mRNA vaccination per 1 million doses (primary outcome).
METHODS: 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 the evaluation of patient medical history, side and range of hearing loss, and hearing recovery outcomes after a minimum period of 3 months. The quantification of hearing loss and assessment of hearing recovery outcomes were performed according to a grading system modified from the Siegel criteria. A cutoff of 21 days was used for the delay onset of SSNHL. The primary outcome was estimated using the total number of doses of each vaccine administered during the study period in France as the denominator.
RESULTS: From 400 extracted cases for tozinameran and elasomeran, 345 (86.3%) spontaneous reports were selected. After reviewing complementary data, 49.6% (171/345) of documented cases of SSNHL were identified. Of these, 83% (142/171) of SSNHL cases occurred after tozinameran vaccination: Rr=1.45/1,000,000 injections; no difference for the rank of injections; complete recovery in 22.5% (32/142) of cases; median delay onset before day 21=4 days (median age 51, IQR 13-83 years); and no effects of sex. A total of 16.9% (29/171) of SSNHL cases occurred after elasomeran vaccination: Rr=1.67/1,000,000 injections; rank effect in favor of the first injection (P=.03); complete recovery in 24% (7/29) of cases; median delay onset before day 21=8 days (median age 47, IQR 33-81 years); and no effects of sex. Autoimmune, cardiovascular, or audiovestibular risk factors were present in approximately 29.8% (51/171) of the cases. SSNHL was more often unilateral than bilateral for both mRNA vaccines (P<.001 for tozinameran; P<.003 for elasomeran). There were 13.5% (23/142) of cases of profound hearing loss, among which 74% (17/23) did not recover a serviceable ear. A positive rechallenge was documented for 8 cases.
CONCLUSIONS: 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. Therefore, it is essential to properly characterize postinjection SSNHL, especially in the case of a positive rechallenge, to provide appropriate individualized recommendations.