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Many Covid-19 patients have reported symptoms affecting their ears, including hearing loss and tinnitus
.
Dizziness and balance problems may also occur, which indicates that the SARS-CoV-2 virus may infect the inner ear
A new study from the Massachusetts Institute of Technology (MIT) and the Massachusetts Eye and Ear Institute provides evidence that the virus does infect cells in the inner ear, including hair cells that are essential for hearing and balance
.
The researchers also found that the pattern of infection seen in human inner ear tissue is consistent with the symptoms seen in a study of 10 Covid-19 patients who reported various ear-related symptoms
The researchers used a new type of human inner ear cell model they developed, as well as hard-to-obtain adult human inner ear tissue for research
.
The limited availability of such organizations has hindered previous research on Covid-19 and other viruses that can cause hearing loss
Lee Gehrke, a professor of medical engineering at the Massachusetts Institute of Technology, said: "Having these models is the first step.
This work opens the way for the study of SARS-CoV-2 and other viruses that affect hearing
.
" He is Co-leader of this research
Konstantina Stankovic was an associate professor at Harvard Medical School and director of the Department of Otolaryngology at the Massachusetts Eye and Ear College.
He is now a professor at the Bertarelli Foundation and chair of the Department of Otorhinolaryngology-Head and Neck Surgery at Stanford University School of Medicine, co-leading the research
.
Minjin Jeong, a former postdoctoral fellow in Stankovic's laboratory at Harvard Medical School and a postdoctoral fellow at Stanford Medical School, is the lead author of the paper, which was published in Communications Medicine on October 29, 2021
Ear infection model
Before the start of the Covid-19 pandemic, Gehrke and Stankovic began a collaborative project to develop cell models to study human inner ear infections
.
Viruses such as cytomegalovirus, mumps virus, and hepatitis virus can cause deafness, but how they cause deafness is unclear
In early 2020, after the SARS-CoV-2 virus appeared, the researchers changed their plans
.
At the Massachusetts Eye and Ear Hospital, Stankovic began treating patients with hearing loss, tinnitus, and dizziness, who tested positive for Covid-19
She and Gehrke decided to use the model system they were working on to study SARS-CoV-2 infection
.
They created cell models by extracting human skin cells and converting them into induced pluripotent stem cells
These cells can grow in a flat two-dimensional layer, or they can be organized into three-dimensional organoids
.
In addition, the researchers obtained some hard-to-obtain samples of inner ear tissue.
Patients with these inner ear tissues are undergoing surgery because of a disease that causes severe dizziness, or a tumor that causes hearing loss and dizziness
.
In human inner ear samples and stem cell-derived cell models, the researchers found that certain types of cells—hair cells and Schwann cells—express the proteins necessary for the SARS-CoV-2 virus to enter the cell
.
These proteins include the ACE2 receptor found on the cell surface, as well as two enzymes, furan and the transmembrane protease serine 2, which help the virus to fuse with the host cell
.
The researchers then discovered that this virus can actually infect the inner ear, especially the hair cells, and to a lesser extent Schwann cells
.
They found that other cell types in the model are not sensitive to SARS-CoV-2 infection
.
The human hair cells studied by the researchers are vestibular hair cells, which are involved in sensing head movement and maintaining balance
.
Cochlear hair cells related to hearing are difficult to obtain or produce in cell models
.
However, the researchers showed that mouse cochlear hair cells also contain proteins that allow SARS-CoV-2 to enter
.
Virus connection
The infection pattern the researchers found in their tissue samples appeared to be consistent with the symptoms of 10 Covid-19 patients who reported ear-related symptoms after infection
.
Nine of these patients had tinnitus, six had dizziness, and all experienced mild to severe hearing loss
.
Damage to cochlear hair cells can cause hearing loss, which is usually assessed by measuring otoacoustic emissions
.
Otoacoustic emission is the sound made by sensory hair cells in response to auditory stimuli
.
Of the six Covid-19 patients who underwent this test in the study, all of them had reduced or no otoacoustic emissions
.
Although this study strongly suggests that Covid-19 may cause hearing and balance problems, the overall proportion of Covid-19 patients experiencing ear-related problems is unclear
.
Stankovic said: "Initially, this was because routine testing was not easy for patients diagnosed with Covid, and when patients had more life-threatening complications, they would not pay too much attention to whether their hearing loss or whether There is tinnitus
.
We still don’t know what the incidence is, but our findings do call for more attention to the hearing symptoms of people who have been exposed to the new coronavirus
.
"
Possible ways for the virus to enter the ear include the Eustachian tube connecting the nose and middle ear
.
Stankovic said the virus may also escape from the nose through small openings around the olfactory nerve
.
This will allow it to enter the brain space and infect the cranial nerves, including the cranial nerves that connect to the inner ear
.
2D and 3D external organoids were used to observe SARS-CoV-2 infection in the inner ear
.
This provides a powerful platform to study the effects of many other exposures on the inner ear, including other infections, toxins, and cancer
.
Researchers now hope to use their human cell model to test possible treatments to treat inner ear infections caused by SARS-CoV-2 and other viruses
.
Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19 -associated audiovestibular dysfunction