Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>COVID-19 is a pandemic respiratory and vascular disease caused by SARS-CoV-2 virus. There is a growing number of sensory deficits associated w...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/150483 |
| _version_ | 1811072120502878208 |
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| author | Jeong, Minjin Ocwieja, Karen E Han, Dongjun Wackym, P Ashley Zhang, Yichen Brown, Alyssa Moncada, Cynthia Vambutas, Andrea Kanne, Theodore Crain, Rachel Siegel, Noah Leger, Valerie Santos, Felipe Welling, D Bradley Gehrke, Lee Stankovic, Konstantina M |
| author2 | Harvard-MIT Program in Health Sciences and Technology |
| author_facet | Harvard-MIT Program in Health Sciences and Technology Jeong, Minjin Ocwieja, Karen E Han, Dongjun Wackym, P Ashley Zhang, Yichen Brown, Alyssa Moncada, Cynthia Vambutas, Andrea Kanne, Theodore Crain, Rachel Siegel, Noah Leger, Valerie Santos, Felipe Welling, D Bradley Gehrke, Lee Stankovic, Konstantina M |
| author_sort | Jeong, Minjin |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Our results provide mechanistic explanations of audiovestibular dysfunction in COVID-19 patients and introduce hiPSC-derived systems for studying infectious human otologic disease.</jats:p>
</jats:sec> |
| first_indexed | 2024-09-23T09:01:13Z |
| format | Article |
| id | mit-1721.1/150483 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:01:13Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1504832023-04-12T03:48:43Z Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction Jeong, Minjin Ocwieja, Karen E Han, Dongjun Wackym, P Ashley Zhang, Yichen Brown, Alyssa Moncada, Cynthia Vambutas, Andrea Kanne, Theodore Crain, Rachel Siegel, Noah Leger, Valerie Santos, Felipe Welling, D Bradley Gehrke, Lee Stankovic, Konstantina M Harvard-MIT Program in Health Sciences and Technology <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our results provide mechanistic explanations of audiovestibular dysfunction in COVID-19 patients and introduce hiPSC-derived systems for studying infectious human otologic disease.</jats:p> </jats:sec> 2023-04-11T14:15:09Z 2023-04-11T14:15:09Z 2021 2023-04-11T14:11:10Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/150483 Jeong, Minjin, Ocwieja, Karen E, Han, Dongjun, Wackym, P Ashley, Zhang, Yichen et al. 2021. "Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction." Communications Medicine, 1 (1). en 10.1038/S43856-021-00044-W Communications Medicine Creative Commons Attribution http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Jeong, Minjin Ocwieja, Karen E Han, Dongjun Wackym, P Ashley Zhang, Yichen Brown, Alyssa Moncada, Cynthia Vambutas, Andrea Kanne, Theodore Crain, Rachel Siegel, Noah Leger, Valerie Santos, Felipe Welling, D Bradley Gehrke, Lee Stankovic, Konstantina M Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction |
| title | Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction |
| title_full | Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction |
| title_fullStr | Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction |
| title_full_unstemmed | Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction |
| title_short | Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction |
| title_sort | direct sars cov 2 infection of the human inner ear may underlie covid 19 associated audiovestibular dysfunction |
| url | https://hdl.handle.net/1721.1/150483 |
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