Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction.

BACKGROUND: COVID-19 is a pandemic respiratory and vascular disease caused by SARS-CoV-2 virus. There is a growing number of sensory deficits associated with COVID-19 and molecular mechanisms underlying these deficits are incompletely understood. METHODS: We report a series of ten COVID-19 patients with audiovestibular symptoms such as hearing loss, vestibular dysfunction and tinnitus. To investigate the causal relationship between SARS-CoV-2 and audiovestibular dysfunction, we examine human inner ear tissue, human inner ear in vitro cellular models, and mouse inner ear tissue. RESULTS: We demonstrate that adult human inner ear tissue co-expresses the angiotensin-converting enzyme 2 (ACE2) receptor for SARS-CoV-2 virus, and the transmembrane protease serine 2 (TMPRSS2) and FURIN cofactors required for virus entry. Furthermore, hair cells and Schwann cells in explanted human vestibular tissue can be infected by SARS-CoV-2, as demonstrated by confocal microscopy. We establish three human induced pluripotent stem cell (hiPSC)-derived in vitro models of the inner ear for infection: two-dimensional otic prosensory cells (OPCs) and Schwann cell precursors (SCPs), and three-dimensional inner ear organoids. Both OPCs and SCPs express ACE2, TMPRSS2, and FURIN, with lower ACE2 and FURIN expression in SCPs. OPCs are permissive to SARS-CoV-2 infection; lower infection rates exist in isogenic SCPs. The inner ear organoids show that hair cells express ACE2 and are targets for SARS-CoV-2. CONCLUSIONS: Our results provide mechanistic explanations of audiovestibular dysfunction in COVID-19 patients and introduce hiPSC-derived systems for studying infectious human otologic disease.

Implementation of Mobile Audiometry During the COVID-19 Pandemic.

During the COVID-19 pandemic, the utility of portable audiometry became more apparent as elective procedures were deferred in an effort to limit exposure to health care providers. Herein, we retrospectively evaluated mobile-based audiometry in the emergency department and outpatient otology and audiology clinics. Air conduction thresholds with mobile audiometry were within 5 dB in 66% of tests (95% CI, 62.8%-69.09%) and within 10 dB in 84% of tests (95% CI, 81.4%-86.2%) as compared with conventional audiometry. No significant differences were noted between mobile-based and conventional audiometry at any frequencies, except 8 kHz (P < .05). The sensitivity and specificity for screening for hearing loss were 94.3% (95% CI, 91.9%-96.83%) and 92.3% (95% CI, 90.1%-94.4%), respectively. While automated threshold audiometry does not replace conventional audiometry, mobile audiometry is a promising screening tool when conventional audiometry is not available.