By Tracie White, Science Writer, Stanford Health Care, School of Medicine

Early into the pandemic, Konstantina Stankovic, MD, PhD, an inner ear researcher, and otolaryngologist, was surprised when she began seeing patients exposed to COVID-19 in her Massachusetts clinic complaining of hearing loss, ringing in the ears known as tinnitus, and dizziness, which often starts in the inner ear.

Related article: COVID-19 and Its Possible Impact on the Audiovestibular System

Sure, everyone had heard about other odd sensory side effects, such as loss of taste and smell, because of the disease, but hearing loss? That wasn’t even on most people’s radar.

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Now, after months of research which culminated in the recent publication of a study in Communications Medicine which links the coronavirus with hearing and balance disorders, Stankovic believes these symptoms should be on everybody’s radar. 

“Our study showed evidence that the SARS-CoV-2 virus that causes COVID-19 can directly infect the inner ear,” Stankovic said. “During the peak of the pandemic, when patients were having more life-threatening complications, they weren’t paying much attention to whether their hearing was reduced or whether they had vertigo. It was easy to dismiss these symptoms as just being a coincidence, and routine testing for SARS-CoV-2 was not yet available.”

Stankovic recommends that hearing tests be routine for anyone diagnosed with COVID-19. Or, if a patient presents with new-onset hearing loss, tinnitus, or vertigo, and has had any exposure to the virus, they should be tested and monitored for worsening symptoms by their healthcare provider.

Other researchers have begun to explore the possible connection between the coronavirus and hearing loss, but no one knows for sure how widespread the problem is, Stankovic said.

The team didn’t study how the coronavirus might be getting into the inner ear, but they speculate the nose is a likely culprit in most people. There’s little concern that the virus enters through the outer ear.

Stankovic, previously at Harvard, recently joined Stanford Medicine as the Bertarelli Foundation Professor and chair of the Department of Otolaryngology-Head and Neck Surgery. She co-led the study while at Harvard with Lee Gehrke, PhD, a professor at the Massachusetts Institute of Technology.

Secrets hidden beneath the skull bone

Before the COVID-19 pandemic began, Stankovic and Gehrke were working together to develop human cellular models for studying inner ear infections. It’s clear that viruses such as mumps, chickenpox, measles, and hepatitis can cause deafness by infecting the inner ear, but the molecular underpinnings of how this happens are not well understood. 

When the pandemic hit, and Stankovic began seeing COVID-19 patients with hearing complaints, she and Gehrke switched gears and focused on determining whether SARS-CoV-2 could, like these other viruses, infect the inner ear.

Their first cellular models were created by transforming human skin cells into induced pluripotent stem cells and differentiating these stem cells into several types of cells found in the inner ear. The inner ear cells grew in two dimensions or self-organized into three-dimensional organoids, mini models of an organ in a dish. Next, they obtained tissue samples from the inner ears of patients who underwent unrelated inner ear surgeries. 

“We initially focused on determining whether human inner ear cells express the proteins that allow the virus to infect the cells,” Stankovic said. “This isn’t straightforward to do since, under normal circumstances, the human inner ear cannot be biopsied because the organ is tiny and would be irreversibly damaged in the process of tissue biopsy.  We’re talking about something the size of the upper part of Lincoln’s face on a penny.”

Finding the path inside

Using the cellular models and the tissue samples, the researchers identified the ingredients — the proteins that make it possible for SARS-CoV-2 to infect the inner ear. 

Armed with that knowledge, the researchers then exposed the inner ear cells to the actual SARS-CoV-2 virus. At 48 hours after infection, they observed that inner ear cells had become infected, according to the study.

The researchers 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.

Original Paper: Jeong M, Ocwieja KE, Han D, et al. Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction. Communications Medicine. 2021;1(44).

Source: Stanford Medicine, Communications Medicine