SARS-CoV-2 Infection of the Inner Ear May Underlie COVID-19-Associated Audiovestibular Dysfunction

Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction | Communications Medicine (nature.com)

Abstract
Background

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.

Methods
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.

Results
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.

Conclusions
Our results provide mechanistic explanations of audiovestibular dysfunction in COVID-19 patients and introduce hiPSC-derived systems for studying infectious human otologic disease.

Plain language summary
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus SARS-CoV-2. A growing number of sensory symptoms have been linked to this illness. Here, we describe patients with COVID-19 and new-onset of hearing loss, tinnitus and/or dizziness. To examine the underlying molecular mechanisms of these symptoms, we studied human and mouse inner ear tissue. We also generated some of the first human cellular models of infectious inner ear disease. We show that human and mouse inner ear cells have the molecular machinery to allow SARS-CoV-2 entry. We further show that SARS-CoV-2 can infect specific human inner ear cell types. Our findings suggest that inner ear infection may underlie COVID-19-associated problems with hearing and balance.​

Yikes!

 

I got the answer of my first question: how did they manage to collect inner ear tissue?

"To evaluate the expression of SARS-CoV-2 receptors in the human inner ear, fresh inner ear tissue was collected during surgical labyrinthectomies and translabyrinthine resections of vestibular schwannomas (N = 6)."

But it led me to my second question: is a fresh inner tissue collected close to a vestibular schwanomma a safe and representative sample of inner ear tissue?

And then further in the text, I read something I am not sure to understand: they did another procedure and they managed to get inner ear organoid differentiation based on skin biopsies.

Well can someone help me to understand?

 

Well that's already a known known. You can go deaf or get tinnitus from a severe bout of flu -- belongs also to the corona family of viruses. It can happen but it's rare.

The trouble is that COVID-19 is not so rare these days.

 

This is a fundamentally different mechanism, though. Influenza doesn't directly attack the ear, and damage and hearing loss is usually secondary to sinusitis.

COVID-19 is being shown in these studies to directly damage olefactory and audiological nerves, because it binds to ACE2 which is all over your body, compared to influenza which is more laser targeted on epithelial cells in the lungs.

Which is to say, COVID-19 appears to be causing hearing damage and tinnitus at a much higher rate than flu (5-15% of cases have persisting hearing issues).

 

This is exactly my case.