• The use of irradiated homologous cartilage for the restoration of facial contour defects remains a controversial issue in reconstructive surgery. Both favorable and unfavorable reports can be found in the literature. Some basic research concerning the rate and mechanism of resorption has been completed but has failed to resolve the issue of the usefulness of this material in day-to-day practice. One frequently cited reference concerning the use of irradiated homologous cartilage in reconstructive surgery was coauthored by two of the present investigators ten years ago. In an effort to place this study in a long-term perspective, we examined 42 of the original 107 patients who formed the initial population base. Sixty-two of the original 145 irradiated homologous cartilage grafts have been followed up for an average of nine years, with an average resorption rate of approximately 75%. Eighteen of 24 grafts followed up from 11 to 16 years completely resorbed. In spite of complete graft resorption, some patients have maintained satisfactory facial contour with fibrous tissue replacement of the cartilage. (Arch Otolaryngol Head Neck Surg1988;114:291-295)

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.