Introduction
Sudden onset sensorineural hearing loss (SSNHL) is a common presentation to otolaryngology emergency clinics, with a reported incidence of 27 per 100,000 in the United States.Reference Alexander and Harris1 SSNHL is defined as a decline of 30dB in greater than or equal to three frequencies in less than 72 hours and tends to present unilaterally.Reference Chandrasekhar, Tsai, Schwartz, Bontempo, Faucett and Finestone2 Although its aetiology remains poorly understood, two proposed mechanisms include viral infection and microvascular occlusion.Reference Schreiber, Agrup, Haskard and Luxon3
Early in the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, numerous cases of SSNHL were reported in patients with positive SARS-CoV-2 tests.Reference Chandrasekhar, Tsai, Schwartz, Bontempo, Faucett and Finestone2–Reference Horby, Lim, Emberson, Mafham, Bell and Linsell6 SARS-CoV-2 has the potential to induce SSNHL via both of the putative mechanisms of SSNHL as a viral infection that is known to induce a coagulopathic state.Reference Conway, Mackman, Warren, Wolberg, Mosnier and Campbell4 However, it is unclear whether SSNHL associated with SARS-COV-2 has different audiometric outcomes to SSNHL from other causes.
Steroids are the traditional mainstay of treatment for SSNHL and are commonly administered either systemically or topically via intratympanic injections. Despite the suspected mechanism of disease, antivirals are not beneficial.Reference Awad, Huins and Pothier5 Early in the pandemic, there was concern regarding the safety of administering systemic steroids to patients with concurrent COVID-19 infection due to potential immunosuppression. This posed a possible treatment dilemma for patients with concurrent COVID-19 infection and associated SSNHL, though this concern was subsequently allayed by the results of the RECOVERY trial, which demonstrated a beneficial role for steroids in particular groups of patients with COVID-19.Reference Horby, Lim, Emberson, Mafham, Bell and Linsell6
This review aims to evaluate what evidence there is for the treatment of SARS-CoV-2 associated SSNHL with corticosteroids and its outcomes.
Methods
An Ovid search was conducted on the 13/11/2024, using MEDLINE and Embase. The following MeSH search terms were used [“Coronavirus 2019” OR “Severe acute respiratory syndrome coronavirus 2”] AND [“Corticosteroid” OR “Steroid”] AND [“Hearing Impairment” OR “Sudden deafness” OR “Perception deafness”].
Search results were screened for suitability by a single reviewer. Inclusion criteria were a positive SARS-CoV-2 polymerase chain reaction result, a diagnosis of SSNHL, and treatment with corticosteroids. Exclusion criteria were any alternative treatment to corticosteroids, treatmentpathway not being reported, non-English language studies, post-vaccination symptoms rather than primary SARS-COV2 infection, and no post-treatment follow-up reported.
Studies were assessed for risk of bias using the Joanna Briggs Institute (JBI) Critical Appraisal Tools for use in JBI systematic reviews, Checklist for Case Reports. The tool has eight questions which are summarised in Table 1.Reference Gagnier, Kienle, Altman, Moher, Sox and Riley7 The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used to standardise reporting of this systematic review.Reference Page, McKenzie, Bossuyt, Boutron, Hoffman and Mulrow8 Given the heterogenous nature of the studies found, data were not synthesised into a meta-analysis.
Assessment of risk of bias
Results
Of the 99 papers identified, 14 met our inclusion criteria and were included in this review. The search strategy is illustrated in Figure 1. Collectively these studies included 154 patients, and their characteristics are summarised in Table 2.Reference Lang, Hintze and Conlon9–Reference Peron, Scott, Soeiro, JBd, Chandrasekhar and Penido Nd22 Notably, no randomised controlled trial evidence was available.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart showing search strategy for studies.
Reported cases of SARS-CoV-2 positive patients presenting with SSNHL
Abbreviations: OD = once a day; PTA = pure tone audiogram; SSNHL = sudden onset sensorineural hearing loss.
Nine of the studies were case reports of individual patients, of whom eight had unilateral SSNHL and one had bilateral SSNHL. Treatments varied greatly between these studies: one participant received only oral corticosteroids with some minor audiometric improvement of up to 15 dB, but persistent severe hearing lossReference Lang, Hintze and Conlon9; one participant received only intratympanic steroid injections reporting improvement of 30-55 dB across all frequencies, but persistent moderate hearing lossReference Rahimi, Rouhbakhsh and Asiyabar10; two case reports used both oral and intratympanic steroids with mixed results.Reference Lang, Hintze and Conlon9, Reference Koumpa, Forde and Manjaly11 One of the cases had partial improvement after 7 days of oral prednisolone and no further improvement following three subsequent rescue intratympanic injections.Reference Koumpa, Forde and Manjaly11 The other patient received simultaneous oral and intratympanic steroids and experienced complete audiometric recovery.Reference Lamounier, Gonçalves, Ramos, Gobbo, Costa and Teixeira12 Additionally, Beckers et al. carried out a study where one participant received sequential intravenous, oral, and then intratympanic steroids, with limited change in hearing thresholds and persistent severe-to-profound hearing loss.Reference Beckers, Chouvel, Cassetto and Mustin18 Rhman et al. investigated the use of an intratympanic injection of methylprednisolone 40 mg/ml, 3 sessions with 5 days apart. There was marked improvement in hearing which was tested 7 days after the last injection.Reference Rhman and Wahid20
Yaseen et al. performed a larger case-series of 26 patients, 18 with bilateral and 8 with unilateral hearing loss.Reference Yaseen, Al-Ani and Ali Rashid14 Patients received a 3-week tapering course of oral prednisolone with the addition of intratympanic steroid injections if no improvement after oral treatment. A partial improvement in hearing thresholds was reported for half of the participants; however, follow-up with pure tone audiograms does not appear to have been at a standardised time. In addition, it is not documented how many patients received salvage intratympanic steroid injections and the effect on the outcome that this had.
Tsuda et al. carried out a larger case-series of 68 patients managed with either a 7-day course of intravenous hydrocortisone (n = 46) or four intratympanic steroid injections, where they received an injection on day 1, 4, 8 and 11, under local anaesthesia as out-patients (n = 22). Additionally, nine patients received further therapy with hyperbaric oxygen and/or defibrinogen therapy due to insufficient improvement after their steroid treatment. Approximately two-thirds of patients had a greater than or equal to 30 dB improvement with either treatment option. Both treatments had a reasonable safety profile with the most common side effect of systemic treatment being insomnia, affecting 19 participants. Other reported side effects included hypertension in two individuals and one case of gastritis. For intratympanic injections, one instance of persistent tympanic membrane perforation was reported but no systemic side effects.Reference Tsuda, Hanada, Wada, Fujiwara, Takeda and Nishimura19
Peron et al. carried out a trial with 15 patients who had tested positive for coronavirus disease 2019 (Covid-19) and had reported SSNHL. Treatment involved oral prednisolone, 1 mg/kg/day, for 14 days with a 3-week tapering course. Of these patients, six had bilateral SSNHL, and nine had unilateral SSNHL. Of this patient group, those with unilateral SSNHL had a greater improvement in hearing when compared to those with bilateral SSNHL. This study also had participants who were diagnosed with SSNHL but did not have a positive Covid-19 test, including 37 patients with a mix of unilateral and bilateral SNHL. When comparing bilateral SSNHL, the Covid-19 positive group showed no significant improvement in hearing after the course of steroids; however, the group who were COVID-19 negative showed significant improvement in audiological thresholds after treatment. This study demonstrates that bilateral SSNHL with a positive history of Covid-19 showed the worst hearing recovery among the subgroups. In those with unilateral SSNHL, there was improvement in hearing after steroid treatment, regardless of status of Covid-19 infection.Reference Peron, Scott, Soeiro, JBd, Chandrasekhar and Penido Nd22
Swain et al. carried out a study with 16 patients involved. In this study, all diagnosed cases of SSNHL associated with a Covid-19 infection were treated with oral prednisolone in the tapering dose, along with vitamin B with folic acid, and proton pump inhibitor daily. From the participants, nine patients (56 percent) showed complete resolution of hearing.Reference Swain, Das and Lenka21
Discussion
The published literature on SARS-CoV-2 associated SSNHL remains sparse. Management strategies are heterogenous between centres, incorporating oral, intravenous and intratympanic steroids both independently and in combination. Furthermore, dosing strategies and treatment duration vary between studies for each administration route. The timing and frequency of follow-up pure tone audiograms also varied between studies. This review presents weak evidence in the form of case reports and series of a modest improvement in hearing thresholds associated with steroid therapy. The full natural history and any late effects of SARS-CoV-2 associated SSNHL remain unknown.
There is no current evidence of superiority between oral, intratympanic and intravenous steroids for the management of SARS-CoV-2 associated SSNHL. The frequent combination of systemic and intratympanic steroids limits our ability to compare treatment outcomes. However, systemic steroid administration does bring a higher risk of side effects.Reference Zhao, Tong, Wang, Hellstrom and Duan23 One case series reported several systemic side effects including sleep disturbance, hypertension and gastritis in those receiving intravenous steroids. Whereas the only reported adverse effect of intratympanic steroid injection was a single case of persistent perforation (4.5 percent).Reference Tsuda, Hanada, Wada, Fujiwara, Takeda and Nishimura19 It is common practice in the UK to offer oral steroids as first line management for SSNHL followed by salvage intratympanic steroid injections, although the evidence base remains contradictory.Reference Horby, Lim, Emberson, Mafham, Bell and Linsell6, Reference Plontke, Meisner, Agrawal, Cayé-Thomasen, Galbraith and Mikulec24 NICE guidelines state that the treatment guidelines for idiopathic SSNHL should consider a steroid, form not specified.25
In the reviewed literature, only 63 patients (41 percent) treated with steroids were reported to have complete resolution of their hearing loss. This is substantially lower than the previously reported 65 percent natural resolution rate of SSNHLReference Mattox and Simmons26 and may reflect a worse prognosis of SARS-CoV-2 associated SSNHL. There have certainly been cases of severe-to-profound hearing loss associated SARS-CoV-2 that have been refractory to treatment with both oral and intratympanic steroids.Reference Edwards, Muzaffar, Naik and Coulson13, Reference Beckers, Chouvel, Cassetto and Mustin18 Indeed, one centre reported a 25 percent rate of “dead ear” in a case series of 12 participants with SARS-CoV-2 associated SSNHL with minimal response to intratympanic steroids,Reference Edwards, Muzaffar, Naik and Coulson13, Reference Mohammed, Ahmad and Banerjee27 a larger study of 26 patients reported at least partial resolution of hearing loss in half of participants.Reference Yaseen, Al-Ani and Ali Rashid14 In common with non–SARS-CoV-2 associated SSNHL, evidence suggests that the presence of severe tinnitus may be a poor prognostic sign.Reference Edwards, Muzaffar, Naik and Coulson13
It is important to consider potential confounding factors to explain this variation, such as a lack of consistent follow-up during the pandemic. In addition, there remains a possibility that symptoms may have improved outside of their study period; however, the majority of instances of spontaneous resolution of SSNHL have been reported to be within 14 days of symptom onset, a timeframe which was covered by most studies.Reference Mattox and Simmons26
Regarding future research directions, the UK’s ENT trainee research collaborative (INTEGRATE) have completed a national prospective multi-centre cohort study (the SeaSHel study) to define optimal patient pathways for SSNHL and develop a tool to predict recovery. Following on from this, the STARFISH trial is recruiting to investigate the optimal route of steroid delivery for the management of idiopathic SSNHL.Reference Smith, Knappett, Vickers, White, Schramm and Mehta28 Subgroup analysis of preceding SARS-CoV-2 status would help answer questions raised by the presently sparse literature on this important topic.
• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) associated sudden onset sensorineural hearing loss (SSNHL) has no specific evidence for its treatment.
• Systemic and intratympanic steroids have been used with reported improvements in audiological symptoms; however, there is great heterogeneity in drug formulations, doses, and treatment duration used.
• Only 41 percent (63/154) patients in this review achieved complete resolution of their symptoms following steroid treatment.
• In the limited data available, patients with SSNHL associated with SARS-CoV-2 infection demonstrate worse reported audiometric outcomes than those with SSNHL due to other causes, but included studies lacked sufficient power for formal inferential statistical testing.
Conclusions
It is important to consider that the consensus outlined in this review is likely to change in the near future as more literature is published on the subject. In the absence of better evidence, treatment of SARS-CoV-2-induced SSNHL with oral and intratympanic steroids seems to be associated with improvements in audiological thresholds and symptoms but gross heterogeneity in practice during the pandemic precludes definition of the optimum formulation, dose, and timing of delivery, as well as a small sample of literature being available. The limited existing literature suggests that patients with SSNHL secondary to SARS-CoV-2 may have worse audiometric outcomes than patients with SSNHL due to other causes, but the present studies are not sufficiently powered for formal statistical analysis.
Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Funding statement
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
Conflict of interest statement
The authors have no potential conflicts of interest with respect to the research, authorship and/ or publication of this article.
Author contributions
M.F.: investigation and writing – original draft. B.T.: writing – original draft. N.D.: supervision, writing – review and editing. M.M.: conceptualisation, writing – review and editing, and supervision.
