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.

Considerations in Management of Acute Otitis Media in the COVID-19 Era.

OBJECTIVES: To present the otologic findings of a patient with COVID-19 and complicated acute otitis media, evaluate for the presence of SARS-CoV-2 in middle ear fluid, and assess whether suctioning of middle ear fluid may be aerosol- generating. METHODS: The case of a man with SARS-CoV-2 infection and complicated acute otitis media with facial paralysis is presented to illustrate unique clinical decisions made in context of the COVID-19 pandemic. A cadaveric temporal bone was used to simulate droplet spread during suctioning of fluorescein-labelled middle ear fluid and visualized with a blue-light filter. RESULTS: A 23-year-old male who presented with complicated acute otitis media with facial paralysis was found to have an acute infection with SARS-CoV-2, with positive viral PCR of nasopharyngeal swab, and a negative PCR of the middle ear fluid. He was placed on isolation precautions and treated with myringotomy, topical and systemic antibiotics, and antivirals. Consistent with observations during endonasal suctioning, suctioning of middle ear fluid was not found to be aerosol or droplet generating. CONCLUSION: The case of a patient with active COVID-19 presenting with complicated acute otitis media in whom middle ear fluid was sampled to evaluate the etiology of the infection and the potential middle ear predilection of SARS-CoV-2 is described. This study has implications for the clinical management of patients with both known and unknown SARS-CoV-2 infection who present with ear disease. While middle ear suctioning may not be aerosol-generating, the risk of coughing or prolonged close contact requires heightened precautions during otologic procedures in patients with suspected or confirmed COVID-19.

American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Foundation Guide to Enhance Otologic and Neurotologic Care During the COVID-19 Pandemic.

: This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons' local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions.Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered "urgent," and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.

Aerosol Dispersion During Mastoidectomy and Custom Mitigation Strategies for Otologic Surgery in the COVID-19 Era.

OBJECTIVE: To investigate small-particle aerosolization from mastoidectomy relevant to potential viral transmission and to test source-control mitigation strategies. STUDY DESIGN: Cadaveric simulation. SETTING: Surgical simulation laboratory. METHODS: An optical particle size spectrometer was used to quantify 1- to 10-µm aerosols 30 cm from mastoid cortex drilling. Two barrier drapes were evaluated: OtoTent1, a drape sheet affixed to the microscope; OtoTent2, a custom-structured drape that enclosed the surgical field with specialized ports. RESULTS: Mastoid drilling without a barrier drape, with or without an aerosol-scavenging second suction, generated large amounts of 1- to 10-µm particulate. Drilling under OtoTent1 generated a high density of particles when compared with baseline environmental levels (P < .001, U = 107). By contrast, when drilling was conducted under OtoTent2, mean particle density remained at baseline. Adding a second suction inside OtoTent1 or OtoTent2 kept particle density at baseline levels. Significant aerosols were released upon removal of OtoTent1 or OtoTent2 despite a 60-second pause before drape removal after drilling (P < .001, U = 0, n = 10, 12; P < .001, U = 2, n = 12, 12, respectively). However, particle density did not increase above baseline when a second suction and a pause before removal were both employed. CONCLUSIONS: Mastoidectomy without a barrier, even when a second suction was added, generated substantial 1- to 10-µm aerosols. During drilling, large amounts of aerosols above baseline levels were detected with OtoTent1 but not OtoTent2. For both drapes, a second suction was an effective mitigation strategy during drilling. Last, the combination of a second suction and a pause before removal prevented aerosol escape during the removal of either drape.

Airborne Aerosol Generation During Endonasal Procedures in the Era of COVID-19: Risks and Recommendations.

OBJECTIVE: In the era of SARS-CoV-2, the risk of infectious airborne aerosol generation during otolaryngologic procedures has been an area of increasing concern. The objective of this investigation was to quantify airborne aerosol production under clinical and surgical conditions and examine efficacy of mask mitigation strategies. STUDY DESIGN: Prospective quantification of airborne aerosol generation during surgical and clinical simulation. SETTING: Cadaver laboratory and clinical examination room. SUBJECTS AND METHODS: Airborne aerosol quantification with an optical particle sizer was performed in real time during cadaveric simulated endoscopic surgical conditions, including hand instrumentation, microdebrider use, high-speed drilling, and cautery. Aerosol sampling was additionally performed in simulated clinical and diagnostic settings. All clinical and surgical procedures were evaluated for propensity for significant airborne aerosol generation. RESULTS: Hand instrumentation and microdebridement did not produce detectable airborne aerosols in the range of 1 to 10 µm. Suction drilling at 12,000 rpm, high-speed drilling (4-mm diamond or cutting burs) at 70,000 rpm, and transnasal cautery generated significant airborne aerosols (P < .001). In clinical simulations, nasal endoscopy (P < .05), speech (P < .01), and sneezing (P < .01) generated 1- to 10-µm airborne aerosols. Significant aerosol escape was seen even with utilization of a standard surgical mask (P < .05). Intact and VENT-modified (valved endoscopy of the nose and throat) N95 respirator use prevented significant airborne aerosol spread. CONCLUSION: Transnasal drill and cautery use is associated with significant airborne particulate matter production in the range of 1 to 10 µm under surgical conditions. During simulated clinical activity, airborne aerosol generation was seen during nasal endoscopy, speech, and sneezing. Intact or VENT-modified N95 respirators mitigated airborne aerosol transmission, while standard surgical masks did not.

Demonstration and Mitigation of Aerosol and Particle Dispersion During Mastoidectomy Relevant to the COVID-19 Era.

BACKGROUND: COVID-19 has become a global pandemic with a dramatic impact on healthcare systems. Concern for viral transmission necessitates the investigation of otologic procedures that use high-speed drilling instruments, including mastoidectomy, which we hypothesized to be an aerosol-generating procedure. METHODS: Mastoidectomy with a high-speed drill was simulated using fresh-frozen cadaveric heads with fluorescein solution injected into the mastoid air cells. Specimens were drilled for 1-minute durations in test conditions with and without a microscope. A barrier drape was fashioned from a commercially available drape (the OtoTent). Dispersed particulate matter was quantified in segments of an octagonal test grid measuring 60 cm in radius. RESULTS: Drilling without a microscope dispersed fluorescent particles 360 degrees, with the areas of highest density in quadrants near the surgeon and close to the surgical site. Using a microscope or varying irrigation rates did not significantly reduce particle density or percent surface area with particulate. Using the OtoTent significantly reduced particle density and percent surface area with particulate across the segments of the test grid beyond 30 cm (which marked the boundary of the OtoTent) compared with the microscope only and no microscope test conditions (Kruskall-Wallis test, p = 0.0066). CONCLUSIONS: Mastoidectomy with a high-speed drill is an aerosol-generating procedure, a designation that connotes the potential high risk of viral transmission and need for higher levels of personal protective equipment. A simple barrier drape significantly reduced particulate dispersion in this study and could be an effective mitigation strategy in addition to appropriate personal protective equipment.

Endonasal instrumentation and aerosolization risk in the era of COVID-19: simulation, literature review, and proposed mitigation strategies.

BACKGROUND: International experience with coronavirus 2019 (COVID-19) suggests it poses a significant risk of infectious transmission to skull base surgeons, due to high nasal viral titers and the unknown potential for aerosol generation during endonasal instrumentation. The purpose of this study was to simulate aerosolization events over a range of endoscopic procedures to obtain an evidence-based aerosol risk assessment. METHODS: Aerosolization was simulated in a cadaver using fluorescein solution (0.2 mg per 10 mL) and quantified using a blue-light filter and digital image processing. Outpatient sneezing during endoscopy was simulated using an intranasal atomizer in the presence or absence of intact and modified surgical mask barriers. Surgical aerosolization was simulated during nonpowered instrumentation, suction microdebrider, and high-speed drilling after nasal fluorescein application. RESULTS: Among the outpatient conditions, a simulated sneeze event generated maximal aerosol distribution at 30 cm, extending to 66 cm. Both an intact surgical mask and a modified VENT mask (which enables endoscopy) eliminated all detectable aerosol spread. Among the surgical conditions, cold instrumentation and microdebrider use did not generate detectable aerosols. Conversely, use of a high-speed drill produced significant aerosol contamination in all conditions tested. CONCLUSION: We confirm that aerosolization presents a risk to the endonasal skull base surgeon. In the outpatient setting, use of a barrier significantly reduces aerosol spread. Cold surgical instrumentation and microdebrider use pose significantly less aerosolization risk than a high-speed drill. Procedures requiring drill use should carry a special designation as an "aerosol-generating surgery" to convey this unique risk, and this supports the need for protective personal protective equipment.