Johns Hopkins bone lab studies COVID effects on ears


Elizabeth Landau is a science reporter and communicator living in Washington, D.C. She has actually added to The New York Times, The Washington Post, Quanta Magazine, Smithsonian, and Wired, to name a few publications. Find her on Twitter at @lizlandau.

This story initially included on Undark.

In a narrow medical school corridor, Matt Stewart opened a big cabinet to expose lots of racks stacked with wood boxes and trays, some a minimum of 100 years of ages.

Stewart, high and silver-haired, took out among the trays and flaunted its contents: Thin pieces of human skull bones and the organs of hearing and balance they include, stained tones of pink. Affixed to microscopic lense slides, the physiological bits looked like abstract rubber stamp art, no larger than thumbprints. “Our Johns Hopkins history,” he stated, describing the university’s collection of specimens from more than 5,000 clients.

Stewart’s research study group at Johns Hopkins University in Baltimore had a long, complex journey to make slides like these in 2021. The scientists require these specimens, sliced from the part of skull that houses the inner ear, to ask a basic concern about the unique coronavirus, SARS-CoV-2: Does it straight attack the cells of tissues that make it possible for hearing and balance?

Data on ear issues as they connect to COVID-19, the illness brought on by SARS-CoV-2, is spotty. To date, case reports and little studies have actually discovered that some COVID-19 clients experience considerable and fast hearing loss, calling in the ears called ringing in the ears, or balance problems. Estimates differ on the occurrence of these signs, however since the coronavirus has actually contaminated numerous countless individuals, even a couple of percent of COVID clients experiencing hearing loss would amount to a big boost worldwide. Yet no causal link has actually been drawn in between the unique coronavirus and acoustic signs. Hearing issues aren’t even on lists of COVID-19 signs, brief or long-lasting, released by the Centers for Disease Control and Prevention.

There are numerous possible descriptions for why the illness may be connected with extreme hearing issues, and researchers might never ever identify all of the hidden systems. But scientists like Stewart are pursuing the theory that the infection might be straight harmful inner ear cells. The coronavirus is currently understood to contaminate the cells of the upper nasal cavity, resulting in loss of odor. A comparable procedure may take place in the ear, discussed Stewart, an associate primary medical officer who focuses on inner ear surgical treatment at the Johns Hopkins Hospital.

The ramifications would extend beyond the unique coronavirus. Each year some 90,000 individuals in the United States—that is, 27 out of 100,000—experience unexpected hearing loss from damage to the inner ear, and infections are believed to trigger a number of these cases. Viruses can likewise result in other problems with hearing and balance. But examining why infections trigger these issues has actually long been an obstacle for researchers. To research study these fragile parts, scientists can’t cut up a living individual’s inner ear—the research study would need the elimination of delicate tissue, running the risk of an injury that may lead to overall deafness or vertigo.

The COVID-19 pandemic has actually inspired scientists to establish brand-new methods to tackling this longstanding concern. At Johns Hopkins, Stewart and associates are utilizing cadavers, dissecting the ears utilizing surgical techniques from the 1800s, and more just recently, with a $7,000 diamond-bladed saw. Meanwhile, a different group at the Massachusetts Institute of Technology and the Massachusetts Eye and Ear Infirmary has actually taken on the concern by studying human tissue residues from unusual surgical treatments and by growing inner ear tissue from stem cells—a unique kind of cell that can duplicate and produce organs. The group released early lead to the Nature journal Communications Medicine in October.

Viruses such as SARS-CoV-2, herpes, and the typical cytomegalovirus “all have these tentacles that seem to touch the ear, but nobody’s been able to study them because the ear is so inaccessible,” states virologist Lee Gehrke, a senior author of the Communications Medicine research study and a teacher at both MIT and Harvard University. “So that’s the part that I think I get most excited about,” he stated. “Now we have a way to look at these things in a way that we were not able to do before.”


Cadavers can be difficult to come by since they need donors. But for Stewart’s group, getting cadavers of clients who had actually passed away with COVID-19 wasn’t the most challenging part—Johns Hopkins was at first able to supply 3. The larger obstacle was sticking to CDC standards. Early in the pandemic, when the research study started, nobody understood precisely the length of time the coronavirus might endure under various conditions. The CDC prevented using powered surgical tools like drills, which would be the most apparent option to enter a cadaver’s ear, however likewise might shoot viral particles into the air and position a threat to anybody in the space. Since contemporary tools were out, Stewart needed to rely on surgical methods from the late 1800s, carried out utilizing hand tools that wouldn’t electrically spin up viral particles at high speed.

In an autopsy space, the scientists wore N95 masks and other surgical equipment. On each cadaver, they started by making a cut behind the ear, and after that discovered the triangular opening to the mastoid, a part of the skull that “kind of looks like a beehive with a bunch of air cells and very, very, very thin bone,” Stewart states. They run with a small chisel-like instrument called an osteotome in addition to a set of instruments called curettes, “which look like little sharp ice cream scoops,” states Stewart. The curettes can scrape a portion of a millimeter at a time. From the mastoid they developed a 2-millimeter opening—approximately the width of a spaghetti noodle—into the middle ear. They then swabbed inside with small non reusable brush.

It can take a year for the bones from cadavers to soften enough to be sliced thin. That’s a long period of time to wait in a pandemic.

The Hopkins scientists ultimately discovered the hereditary signature of the SARS-CoV-2 coronavirus in 2 of the 3 cadavers, verifying that the infection can make its method to the middle ear and mastoid. Stewart and associates released these findings in a research study letter in the journal JAMA Otolaryngology-Head & Neck Surgery in July 2020, advising that health care companies use eye security and N95 masks throughout treatments including the middle ear. (In unpublished follow-up research study, the viral signature was discovered in 60 percent of more than 20 cadavers.)

In an e-mail to Undark, Jameel Muzaffar, a cosmetic surgeon and scientist at the University of Cambridge and Oto Health in the U.K., stated he was not amazed by the signature of SARS-CoV-2 in the center ear and mastoid because both structures are connected to the nose, where the coronavirus is understood to focus. Indeed, Stewart states, the infection might have taken a trip with “infected snot” from in other places in the sinuses without always attacking valuable inner ear cells.

The research study does provide assistance to “the idea that as the virus is present in the middle ear, it could more easily access the inner ear,” possibly triggering unexpected hearing loss, Muzaffar states. Still, it did not address the concern: Could the coronavirus straight attack and damage the cells of hearing?

A December 2020 research study in Laryngoscope explored this concern in an organism simpler to analyze than human beings: mice. The unique coronavirus is understood to get in cells by engaging with a receptor called ACE-2, which sits on the surface area of some human cells. Researchers at the University of Tokyo wanted to see if ACE-2 receptors and associated proteins exist in mouse ear structures. It ends up, they are.

That research study “lit a creeping fire under me,” Stewart states. If his group duplicated this in human beings, they would require to slice the inner ear into private thin cross-sections to examine under a microscopic lense. But from the time scientists acquire ear samples from cadavers, it can take a year for the bones to soften enough to be sliced thin. That’s a long period of time to wait in a pandemic.


To take a look at human cells, Stewart’s group would require to make brand-new slides with thin cross-sections of the organs of hearing and balance like the historic ones in the medical school corridor cabinets. In the previous cadaver research study, his group did not have a method to access the inner ear. This time, they’d need to sculpt their method to that fragile location, and make really great cuts.

Stewart reflected to when he studied geochemistry as a college student. Back then, he had actually utilized customized tools to cut into rocks and gems. “So I had the idea to use a diamond mineralogic saw,” Stewart states. Since the density of the blade is simply .03 inches, less product would be lost when cutting into temporal bone—a part of the skull enclosing the inner ear and balance organs. From there, Stewart reasoned, the research study group might quickly decalcify the cut bones with acid to soften them, so that they might reach those delicate hearing and balance organs, slice them thin, and carry out experiments to try to find essential cell receptors.

Stewart looks under a microscopic lense at a temporal bone, which frames the organs of hearing, from a contributed cadaver. Elizabeth Landau / Undark

The diamond-bladed saw expense about $7,000—an uncommon purchase for an ear cosmetic surgeon with a wild concept. While the National Institutes of Health had actually offered financing for Stewart’s previous cadaver research study, the firm decreased to support this unverified strategy, so Stewart straight approached a household that had actually contributed to the health center, asking if they would support using their funds for this job. They did.

Using this strategy, Stewart and associates effectively developed the specimens they required almost 2 weeks after the preliminary surgical treatment. When he returned the very first slide in 2015 in early June, “I just sat back in my office and I felt like I had really accomplished something,” Stewart states. His group had actually prevailed over an essential barrier in searching for receptors that the COVID-triggering infection might assault.

Preliminary results recommend that they’re on the best track. Using temporal bones from 6 cadavers that did not have a COVID-19 infection, the scientists discovered these susceptible cell receptor enters the middle ear, cochlea, and balance system. That indicates the unique coronavirus might possibly trigger hearing damage by straight attacking cells. “That was a big piece of the puzzle,” Stewart states. This has actually not yet been peer-reviewed, however Stewart provided the outcomes at the American Neurotology Society’s conference in September 2021, and his group is preparing a manuscript to send to a journal.


Separately, prior to the pandemic, a group in the Boston location led by cosmetic surgeon Konstantina Stankovic, now at Stanford University, was growing inner ear tissues utilizing a kind of stem cell that aggregates to form clusters called organoids. But it wasn’t till the introduction of COVID that they, in partnership with scientists at MIT, began utilizing these cells to much better comprehend vulnerability to infections.

Under a microscopic lense, the organoid tissues resemble what’s inside a human ear, stated Gehrke, the virologist, who teamed up with Stankovic. The group has actually even grown hair cells, sensory receptors that find motion and make it possible for hearing with small stalks called stereocilia standing out of their surface area. These researchers likewise studied human inner ear tissue from 2 live clients. It originated from an uncommon surgical treatment that relieves crippling vertigo however decreases hearing.

Cells from both the organoids and the clients’ inner ears included the very same proteins that Stewart discovered in his cadaver research study. Gehrke and associates then went one action even more: They exposed both the organoid and the client tissues to SARS-CoV-2. As they forecasted, the unique coronavirus contaminated a few of the cells. “Their work is so important,” Stewart composed in a current e-mail. Gehrke identified Stewart’s initial findings as terrific news. “Any data that are complementary,” he states, are “very useful.”

Because of interaction problems when noises are smothered, a client’s “world kind of contracts.”

Next, Stewart’s group prepares to try to find proof of direct intrusion in the cells of hearing and balance system organs utilizing samples from COVID-19-favorable cadavers. In that method, they might try to find possible interactions in between human tissue and an infection that had actually contaminated it naturally, instead of through an experiment. Stankovic and Gehrke’s group, on the other hand, wish to check speculative treatments in their organoids, Gehrke stated, along with take a look at other infections. Both groups wish to adjust their designs to check out other possible reasons for hearing loss from infections, such as swelling and immune actions.

All of this might one day result in much better treatments and encouraging take care of individuals who deal with hearing and balance problems, Stewart states. The topic is individual for him, as he saw his dad establish hearing loss after years of utilizing dynamite as a field geologist. Because of interaction problems when noises are smothered, Stewart includes, a client’s “world kind of contracts.”

With a higher understanding of how infections engage with the ear, medical professionals will have the ability to much better aid both clients with existing COVID illness too those who have “post-viral effects,” Stewart states.



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