Study finds SARS-CoV-2 virus can infect inner ear
Many novel coronavirus (COVID-19) patients have reported symptoms affecting the ears, including hearing loss and tinnitus. Dizziness and balance problems can also occur, suggesting that the SARS-CoV-2 virus may be able to infect the inner ear, according to a new study from the Massachusetts Institute of Technology and Massachusetts Eye and Ear published in the journal Nature.
The study provides evidence that the virus can infect cells of the inner ear, including hair cells, which are critical for both 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 a variety of ear-related symptoms.
The researchers used novel cellular models of the human inner ear that they developed, as well as hard-to-obtain adult human inner ear tissue, for their studies. The limited availability of such tissue has hindered previous studies of COVID-19 and other viruses that can cause hearing loss.
Before the COVID-19 pandemic, the researchers began working together on a project to develop cellular models to study infections of the human inner ear. Viruses such as cytomegalovirus, mumps virus, and hepatitis viruses can all cause deafness, but exactly how they do so is not well-understood. In early 2020, after the SARS-CoV-2 virus emerged, the researchers altered their plans. At Massachusetts Eye and Ear, practitioners started to see patients who were experiencing hearing loss, tinnitus, and dizziness, who had tested positive for COVID-19.
The researchers decided to use the model system they were working on 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. Then, they were able to stimulate those cells to differentiate into several types of cells found in the inner ear: hair cells, supporting cells, nerve fibers, and Schwann cells, which insulate neurons.
These cells could be grown in a flat, two-dimensional layer or organized into three-dimensional organoids. In addition, the researchers were able to obtain samples of hard-to-obtain inner ear tissue from patients who were undergoing surgery for a disorder that causes severe attacks of vertigo or for a tumor that causes hearing loss and dizziness.
In both the human inner ear samples and the stem-cell-derived cellular models, the researchers found that certain types of cells, specifically hair cells and Schwann cells, express the proteins that are needed for the SARS-CoV-2 virus to enter the cells. These proteins include the ACE2 receptor, which is found on cell surfaces, and two enzymes called furin and transmembrane protease serine 2, which help the virus to fuse with the host cell.
The researchers then showed that the virus can infect the inner ear, specifically the hair cells and, to a lesser degree, Schwann cells. They found that the other cell types in their models were not susceptible to SARS-CoV-2 infection.
The human hair cells that the researchers studied were vestibular hair cells, which are involved in sensing head motion and maintaining balance. Cochlear hair cells, which are involved in hearing, are much harder to obtain or generate in a cellular model. However, the researchers showed that cochlear hair cells from mice also have proteins that allow SARS-CoV-2 entry.
The pattern of infection that the researchers found in their tissue samples appears to correspond to the symptoms observed in a group of 10 COVID-19 patients who reported ear-related symptoms following their infection. Nine of these patients suffered from tinnitus, six experienced vertigo, and all experienced mild to profound hearing loss.
Damage to cochlear hair cells, which can cause hearing loss, is usually evaluated by measuring otoacoustic emissions, sounds given off by sensory hair cells as they respond to auditory stimulation. Among the six COVID-19 patients in the study who underwent this testing, all had reduced or absent otoacoustic emissions.
While this study strongly suggests that COVID-19 can cause auditory and balance problems, the overall percentage of COVID-19 patients who have experienced ear-related issues is not known. The researchers said they now hope to use their human cellular models to test possible treatments for the inner ear infections caused by SARS-CoV-2 and other viruses.