key: cord-0991501-bgko35nk authors: Chen, Jiann-Jy; Zeng, Bing-Yan; Lui, Chun-Chung; Chen, Tien-Yu; Chen, Yen-Wen; Tseng, Ping-Tao title: Pfizer–BioNTech COVID-19 vaccine-associated tinnitus and treatment with transcranial magnetic stimulation date: 2022-05-18 journal: QJM DOI: 10.1093/qjmed/hcac124 sha: 39521b03a24dc032650492f94cb918129695800e doc_id: 991501 cord_uid: bgko35nk The COVID-19 vaccine associated tinnitus had become well recognized after its development and widely usage. However, few knowledge about the management to relieve its severity had been few discussed. In the current case report, we present a case who suffered from worsening tinnitus after the second dosage of Pfizer-BioNTech COVID-19 vaccination. The pure tone audiometry (PTA) revealed hearing impairment after this vaccination with increased scores of tinnitus handicap index (THI). This tinnitus respond poorly to the low dosage steroid treatment. After the repetitive transcranial magnetic stimulation (rTMS) treatment, the followed PTA was improved, along with the reduced THI scores. The current report provided a point of view that the anti-inflammatory effect by rTMS might be considered to be an alternative choice to manage COVID-19 vaccine associated tinnitus. Furthermore, in consideration of benefit and this minor and reversible adverse event, we still strongly recommend the continuation of the administration of the Pfizer-BioNTech COVID-19 vaccine. This case report aimed to remind the clinicians of the potentially alternative treatment to manage the cochleopathy after the administration of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine. The repetitive transcranial magnetic stimulation might be beneficial to manage the immune reaction-associated cochleopathy. The COVID-19 vaccine had been recognized as one of the most important weapons to fight COVID-19. However, the COVID-19 vaccine-associated tinnitus, although not a severe adverse event, had attracted the clinicians' attention gradually. 1 Although it had not been well studied, the vaccination-mediated immune reaction was considered to be one of the major reasons of this adverse event. Therefore, the immune-targeted treatment, such as steroid, was considered to be an effective treatment. 2 However, not every patient with COVID-19-associated tinnitus responded well to the steroid treatment. 1 In this case report, we present a case with exacerbated tinnitus after her second dosage Pfizer-BioNTech COVID-19 vaccination, who responded well to the repetitive transcranial magnetic stimulation (rTMS) treatment. Miss A is a 37-year-old female who had a past history of bilateral ovarian chocolate cyst. She started to have bilateral tinnitus since 2020 with a stationary course. She visited our clinics for further tinnitus management at February 2021 with baseline tinnitus handicap index (THI) 92. The high-resolution computed tomography on 26 February 2021 showed mild temporal bone inflammatory change, which was similar with our previous case report. 3 The baseline pure tone audiometry (PTA) on 22 March 2021 showed right extreme high tone mild sensorineural hearing loss and left extreme high tone mild-to-moderate sensorineural hearing loss ( Figure 1A ). She started to receive lowdosage ceftriaxone 1 gm every week since mid-May 2021. Her objective tinnitus symptoms were relieved gradually and followed THI decreased to 12 on 27 September 2021. However, she received her first dosage of Pfizer-BioNTech COVID-19 vaccine There is no any discomfort after this vaccination initially. However, her tinnitus, especially in right ear, started to become worsening since 29-30 November 2021. Her THI increased to 96. The rechecked PTA on 1 December 2021 showed bilaterally worsening hearing threshold around 10-20 db in 11.2K to 16K, especially in right ear ( Figure 1B) . Under the impression of COVID-19 vaccine-associated cochleopathy, 2 she started to receive our steroid protocol: one dose of 10 mg intravenous dexamethasone and a 3-day oral 5 mg prednisolone three times per day since late-December, 2021. However, her tinnitus persisted with minimally improvement (THI minimally decreased to 88). We started to apply 3session rTMS protocol (i.e. 10 Hz rTMS 3000 pulses over left dorsolateral prefrontal cortex one session per day) since 16 February 2022. Her tinnitus decreased to THI 66 on 22 February 2022 and THI 6 on 9 March 2022. The followed PTA at 9 March 2022 showed bilaterally improved hearing threshold in 11.2K to 16K, especially in right ear ( Figure 1C) . This is the first case report addressing the potential beneficial effect of rTMS on COVID-19 vaccine-associated cochleopathy. In this case, the changes of PTA and THI revealed a clear time-course association with the COVID-19 vaccine injection. In our previous network meta-analysis, the rTMS was found to be beneficial to treat tinnitus without specific origin. 4 In this case, the FDA approval rTMS significantly relieve the COVID-19 vaccine-associated cochleopathy. In the previous animal model study, the application of rTMS could contribute to antiinflammatory effect in target and remote brain regions. 5 Although the mechanism of the COVID-19 vaccine-associated tinnitus had not been well-established, the immune-mediated inflammation might play an important role in this situation. 2 Therefore, this would support the findings of significant response of tinnitus to rTMS in this case. We aimed to provide a point of view that effect of anti-inflammation by the rTMS might be considered to be an alternative choice in COVID-19 vaccine-associated tinnitus. Finally, in consideration of benefit and this minor and reversible adverse event, we still strongly recommend the continuation of the administration of the Pfizer-BioNTech COVID-19 vaccine. In general, the baseline PTA revealed right extreme high tone mild sensorineural hearing loss and left exgtreme high tone mild-to-moderate sensorineural hearing loss (A). After COVID-19 vaccine injection, the audiometry revealed bilaterally worsening hearing threshold around 10-20 db in 11.2K to 16K, especially in right ear (B). After the rTMS treatment, the audiometry revealed bilaterally improved hearing threshold in 11.2K to 16K, especially in right ear (C). SARS-CoV-2 vaccine-associated-tinnitus: a review The reversible tinnitus and cochleopathy followed first-dose AstraZeneca COVID-19 vaccination Tinnitus associated with mild osteomyelitis of the temporal bone reversed after conservative antibiotic treatment: a case series Association of central noninvasive brain stimulation interventions with efficacy and safety in tinnitus management: a metaanalysis Repetitive transcranial magnetic stimulation reduces remote apoptotic cell death and inflammation after focal brain injury Conflict of interest. The authors declared that there was no any potential conflict of interest in this work.