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A 45-year-old man presents to the otolaryngology department of the Royal National Throat, Nose and Ear Hospital in London, England, reporting having lost the hearing in his left ear over the previous week while in the hospital receiving treatment for COVID-19. His medical history includes asthma, and he notes that prior to his admission, aside from the asthma, he was fit and well.

The patient explains that he was admitted after 10 days of worsening COVID-19 symptoms, and subsequently was transferred to the intensive care unit (ICU) due to breathing difficulties and was intubated for 30 days. His time in the ICU was further complicated by bilateral pulmonary emboli, ventilator-associated pneumonia, pulmonary hypertension, and anemia.

Treatments for his COVID-19 infection included remdesivir, intravenous steroids, and plasma exchange, which resulted in clinical improvement. He was extubated and transferred out of the ICU. A week later, however, he suddenly developed ringing in his left ear and lost hearing in that ear.

The patient has no previous history of hearing loss or ear pathology. His records show that he was also receiving treatment with teicoplanin and ciprofloxacin during admission, but this was completed 2 days before the hearing loss developed, and no ototoxic medications were administered.

The patient completes a course of oral steroids 60 mg for 7 days, and reports having some improved hearing. Subsequent treatment with three rescue intratympanic injections of 0.5 mL methylprednisolone sodium succinate (125 mg/mL), however, do not seem to have any additional benefits when clinicians test his hearing using pure tone audiograms.

The patient's medication history includes:

• Colecalciferol 20,000 units twice weekly

• Doxazosin 4 mg once daily

• Fluticasone 125 μg 1-2 puffs/day

• Fluticasone propionate 50 μg nasal spray

• Folic acid 5 mg once daily

• Lansoprazole 30 mg once daily

• Loratadine 10 mg once daily

• Ramipril 5 mg once daily

• Rivaroxaban 20 mg once daily

• Salbutamol inhaler as needed

• Tadalafil 10 mg as needed

Clinical examination reveals patent and non-inflamed ear canals, with intact tympanic membranes. Bedside hearing tests suggest left-sided sensorineural hearing loss, with a negative Rinne test on that side and a Weber test lateralizing to the opposite side. He has no additional focal neurology.

Diagnosis is later confirmed with a pure tone audiogram, which shows that 2, 3, 4 and 6 kHz frequencies are the most affected, with elevated hearing thresholds of 65, 75, 75 and 85 dB, respectively.

Subsequent to treatment with oral steroids, the patient receives a series of intratympanic steroid injections. A follow-up pure tone audiogram shows that his hearing has improved somewhat, with thresholds of 55, 60, 60, and 80 dB at 2, 3, 4 and 6 kHz frequencies, respectively.

Laboratory tests performed at the onset of the hearing loss show a white cell count within normal range (7.1) and a slightly elevated C-reactive protein of 346, which the medical team believes is related to the patient's COVID-19 infection.

Findings of a full autoimmune screen including rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, centromere antibody, smooth muscle antibody, and anti-cardiolipin antibody are negative, as are the results of viral screens for influenza and HIV.

Angiotensin-converting enzyme (ACE), immunoglobulins, and complement C3 and C4 are all within normal range, and magnetic resonance imaging of the internal auditory meatus excludes any other explanations for the patient's unilateral hearing loss, which does not improve.

In the absence of any clear etiology to explain the patient's sudden hearing loss, clinicians consider it possible that his symptoms may be related to COVID-19.

Discussion

Clinicians presenting this of rare sudden onset sensorineural hearing loss (SSNHL) following COVID-19 note that it is the first to be reported in the U.K., and that there have been only four other cases previously described anywhere in the literature.

Hearing loss can be a significant cause of morbidity and can easily be missed in the ICU setting, the case authors note. Being aware and screening for SSNHL following COVID-19, therefore, allows early treatment with a course of steroids, and represents the best chance of recovering hearing.

SSNHL – defined as a hearing loss of at least 30 decibels (dB) in at least three consecutive frequencies that develops within a 3-day period – is observed relatively commonly in otolaryngology, with a worldwide incidence of five to 160 cases per 100,000 people annually.

While the etiology is generally not confirmed, presumed causes include viral-related, immune-mediated, cellular stress response, and vascular occlusion pathologies; while herpes species and cytomegalovirus have been linked with hearing loss, these are not commonly considered to cause SSNHL.

Of the cases reported, clinicians cite several in patients with COVID-19 in which physical examination and imaging excluded other causes of hearing loss. One involved a previously healthy 60-year-old man admitted to the ICU due to severe COVID-19 who developed deafness in his right ear along with left-sided sensorineural hearing loss; symptoms were managed with intratympanic steroids and a cochlear implant.

SSNHL is a subject of ongoing research in the field of otolaryngology with questions focused on the optimal route of steroid administration. The case authors note that their patient's symptoms responded well to oral steroids, and there was no further benefit from intratympanic steroid injections. Furthermore, the patient later mentioned having difficulty acknowledging the hearing loss in the busy ICU environment.

Regarding initial assessment of patients with presumptive SSNHL, the most recent strongly recommend against use of routine computed tomography (CT) scan of the head (i.e., nontargeted head CT scan that is often ordered in the emergency department setting for patients presenting with sudden hearing loss). Additionally, the guidelines note that clinicians should not obtain routine laboratory tests in patients with SSNHL or routinely prescribe antivirals, thrombolytics, vasodilators, or vasoactive substances to these patients.

Neuronal inflammation related to COVID-19 has been reported previously in the context of anosmia, but the relationship between COVID-19 and SSNHL has not been thoroughly explored to date.

The case authors cite a of polymerase chain reaction (PCR) testing that showed that of five patients presenting with SSNHL, only one was found to be SARS-CoV-2 positive and had no other new symptoms. However, given the variable sensitivity of SARS-CoV-2 PCR testing – ranging in from 32% to 98% depending on the site and quality of the sample, stage of disease, and viral multiplication and clearance -- the case authors suggest that a higher proportion of those five patients with sensorineural hearing loss may have indeed been previously infected with SARS-CoV-2.

Another 2020 of transient evoked otoacoustic emissions (TEOAEs) in 20 patients who were SARS-CoV-2 positive but who had no COVID-19-related symptoms and 20 control patients found significantly worse high frequency pure tone audiometry thresholds and TEOAE amplitudes among those who were SARS-CoV-2 positive. These findings support a potential association between COVID-19 and cochlear damage, the case authors suggest.

In addition, despite the low numbers of studies, it is important to explore a possible relationship between COVID-19 and SSNHL, the authors note, explaining that histopathological studies of patients with SSNHL have shown loss of hair cells and supporting cells of the organ of Corti without inflammatory cell infiltrate. This suggests that the pathology of idiopathic SSNHL may be related to cellular stress pathways.

SARS-CoV-2 is thought to bind to the ACE-2 receptor, which is present on alveolar epithelial cells and endothelial cells, and more recently was noted in murine models to be expressed in epithelial cells of the middle ear, as well as the stria vascularis and spiral ganglion.

In addition, SARS-CoV-2 causes an inflammatory response and an increase in cytokines such as tumor necrosis factor-alpha and interleukins 1 and 6; direct entry into the cochlea and inflammation leading to cell stress have both been implicated in persistent sensorineural hearing loss, and may have roles in SARS-CoV-2 infection.

While this patient's case is the first to be reported following COVID-19 infection in the U.K., the pandemic nature of the virus coupled with the significant morbidity associated with hearing loss makes further investigation of this possible symptom of COVID-19 crucial, especially at a time when hospital resources may be strained, the case authors emphasize.

They recommend asking COVID-19 patients in intensive case environments about hearing loss when applicable, and referring any patient reporting acute hearing loss to otolaryngology on an emergency basis.

Conclusion

The case authors urge screening for hearing loss in the hospital to avoid missing the treatment window and increasing the possibility of decreasing hearing loss-associated morbidity.

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