A new study from MIT and Massachusetts Eye and Ear supplies evidence that the SARS-CoV-2 infection can infect cells of the inner ear. Credit: Christine Daniloff, MIT
The prevalence of acoustic symptoms in Covid-19 clients is unknown, but infection of the inner ears might be accountable for hearing and balance problems.
Many Covid-19 patients have reported signs impacting the ears, consisting of hearing loss and ringing in the ears. Dizziness and balance problems can also take place, recommending that the SARS-CoV-2 infection may have the ability to infect the inner ear.
A brand-new study from MIT and Massachusetts Eye and Ear supplies proof that the infection can certainly infect cells of the inner ear, consisting of hair cells, which are critical for both hearing and balance. The scientists likewise found that the pattern of infection seen in human inner ear tissue follows the signs seen in a study of 10 Covid-19 patients who reported a range of ear-related signs.
They were able to stimulate those cells to distinguish into several types of cells discovered in the inner ear: hair cells, supporting cells, nerve fibers, and Schwann cells, which insulate neurons.
Possible routes for the infection to go into the ears consist of the Eustachian tube, which connects the nose to the middle ear. That would allow it to get in the brain area and contaminate cranial nerves, consisting of the one that links to the inner ear.
” This post offers very compelling evidence that Sars-CoV-2 contaminates the inner ear, and may be causally associated to the hearing and balance symptoms in a number of clients with Covid-19 infection,” states Yuri Agrawal, a professor of otolaryngology-head and neck surgery at Johns Hopkins School of Medicine, who was not included in the study. “Another amazing advance for our field is the usage of 2D and 3D in vitro organoids to observe Sars-CoV-2 infection of the inner ear.
The researchers used unique cellular designs of the human inner ear that they established, as well as hard-to-obtain adult human inner ear tissue, for their research studies. The minimal availability of such tissue has actually hindered previous research studies of Covid-19 and other infections that can cause hearing loss.
” Having the models is the initial step, and this work opens a path now for working with not just SARS-CoV-2 however likewise other infections that affect hearing,” states Lee Gehrke, the Hermann L.F. von Helmholtz Professor in MITs Institute for Medical Engineering and Science, who co-led the research study.
Konstantina Stankovic, a previous associate professor at Harvard Medical School and former chief of otology and neurotology at Massachusetts Eye and Ear, who is now the Bertarelli Foundation Professor and chair of the Department of Otolaryngology– Head and Neck Surgery at Stanford University School of Medicine, co-led the study. Minjin Jeong, a previous postdoc in Stankovics lab at Harvard Medical School, who is now at Stanford Medical School, is the lead author of the paper, which was published on October 29, 2021, in Communications Medicine.
Designs of ear infection
Before the Covid-19 pandemic began, Gehrke and Stankovic began collaborating on a project to develop cellular models to study infections of the human inner ear. Viruses such as cytomegalovirus, mumps virus, and liver disease viruses can all trigger deafness, but precisely how they do so is not well-understood.
In early 2020, after the SARS-CoV-2 infection emerged, the scientists modified their strategies. At Massachusetts Eye and Ear, Stankovic started to see clients who were experiencing hearing dizziness, tinnitus, and loss, who had evaluated positive for Covid-19. “It was very uncertain at the time whether this was coincidental or causally related, because hearing loss and tinnitus are so typical,” she remembers.
She and Gehrke chose to use the model system they were dealing with to study infection of SARS-CoV-2. They created their cellular models by taking human skin cells and transforming them into induced pluripotent stem cells. They were able to promote those cells to differentiate into a number of types of cells found in the inner ear: hair cells, supporting cells, nerve fibers, and Schwann cells, which insulate nerve cells.
These cells might be grown in a flat, two-dimensional layer or organized into three-dimensional organoids. In addition, the scientists had the ability to get samples of hard-to-obtain inner ear tissue from patients who were going through surgery for a condition that causes serious attacks of vertigo or for a tumor that triggers hearing loss and dizziness.
In both the human inner ear samples and the stem-cell-derived cellular models, the scientists discovered that particular types of cells– hair cells and Schwann cells– reveal the proteins that are needed for the SARS-CoV-2 virus to go into the cells. These proteins include the ACE2 receptor, which is discovered on cell surfaces, and 2 enzymes called furin and transmembrane protease serine 2, which assist the infection to fuse with the host cell.
The researchers then showed that the virus can actually contaminate the inner ear, specifically the hair cells and, to a lower degree, Schwann cells. They found that the other cell enters their designs were not vulnerable to SARS-CoV-2 infection.
The human hair cells that the scientists studied were vestibular hair cells, which are associated with sensing head motion and maintaining balance. Cochlear hair cells, which are included in hearing, are much more difficult to generate or obtain in a cellular model. Nevertheless, the scientists showed that cochlear hair cells from mice also have proteins that enable SARS-CoV-2 entry.
Viral connection
The pattern of infection that the scientists discovered in their tissue samples appears to correspond to the signs observed in a group of 10 Covid-19 patients who reported ear-related symptoms following their infection. Nine of these clients experienced ringing in the ears, 6 knowledgeable vertigo, and all experienced mild to profound hearing loss.
Damage to cochlear hair cells, which can trigger hearing loss, is typically assessed by measuring otoacoustic emissions– sounds emitted by sensory hair cells as they react to auditory stimulation. Amongst the 6 Covid-19 clients in the research study who underwent this screening, all had actually lowered or missing otoacoustic emissions.
While this study strongly suggests that Covid-19 can cause auditory and balance problems, the general percentage of Covid-19 clients who have actually experienced ear-related problems is not known.
” Initially this was since regular testing was not easily available for patients who were detected with Covid, and also, when clients were having more life-threatening problems, they werent paying much attention to whether their hearing was reduced or whether they had tinnitus,” Stankovic says. “We still dont understand what the occurrence is, however our findings truly call for increased attention to audiovestibular symptoms in people with Covid direct exposure.”
Possible routes for the virus to enter the ears consist of the Eustachian tube, which connects the nose to the middle ear. The virus might also be able to leave from the nose through little openings surrounding the olfactory nerves, Stankovic states. That would permit it to get in the brain area and contaminate cranial nerves, including the one that links to the inner ear.
” This article provides extremely compelling proof that Sars-CoV-2 infects the inner ear, and might be causally associated to the hearing and balance symptoms in a variety of clients with Covid-19 infection,” says Yuri Agrawal, a professor of otolaryngology-head and neck surgical treatment at Johns Hopkins School of Medicine, who was not associated with the study. “Another interesting advance for our field is making use of 2D and 3D in vitro organoids to observe Sars-CoV-2 infection of the inner ear. This provides an effective platform to study the effect of a number of other exposures, consisting of other infections, contaminants, and cancers, on the inner ear.”
The researchers now intend to use their human cellular models to test possible treatments for the inner ear infections triggered by SARS-CoV-2 and other infections.
Recommendation: “Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction” by Minjin Jeong, Karen E. Ocwieja, Dongjun Han, P. Ashley Wackym, Yichen Zhang, Alyssa Brown, Cynthia Moncada, Andrea Vambutas, Theodore Kanne, Rachel Crain, Noah Siegel, Valerie Leger, Felipe Santos, D. Bradley Welling, Lee Gehrke and Konstantina M. Stankovic, 29 October 2021, Communications Medicine.DOI: 10.1038/ s43856-021-00044-w.
The research study was funded by the National Institutes of Health, the Remondi Foundation, the Nancy Sayles Day Foundation, and the Barnes Foundation.