From conjunctivitis to vertigo, coronavirus infections can affect disparate senses

Authors:  Emily Sohn SCIENTIFIC AMERICAN

Red eyes, ringing ears, sensitivity to light, trouble hearing: although a loss of taste and smell have become well-known sensory symptoms of COVID, accumulating research suggests that vision and hearing are also frequent targets of SARS-COV-2, the virus that causes the disease.

More than 10 percent of people who get COVID develop some type of eye or ear symptom, according to the latest data, and both categories are among the complaints that can end up persisting for a long time. As researchers work to understand how the virus infiltrates our senses, their findings suggest that people may need to broaden the scope of warning signs for when to get tested. Instead of just a fever, cough or changes in taste and smell, the first signs of illness might include irritated eyes, hearing problems or balance issues.

Nearly two years into the pandemic, research on COVID’s effects on the eyes and ears suggests that scientists have much more to learn about how the virus affects our bodies and nervous systems, experts say. “The data are growing to suggest that there are more neural consequences of this infection than we originally thought,” says Lee Gehrke, a molecular biologist at the Massachusetts Institute of Technology.

THE EYES HAVE IT

One of the first people who tried to warn the world about COVID was Li Wenliang, a Chinese ophthalmologist in Wuhan. He likely caught the virus from an asymptomatic glaucoma patient, according to Bhupendra Patel, of the University of Utah’s John A. Moran Eye Center, who co-authored a 2021 review of research on COVID’s ocular symptoms. Li died from his illness early in 2020, but his case was not the only early clue that eyes might play a role in the virus’s spread. From the beginning of the pandemic, reports included red eyes as a common symptom.

That was not surprising to scientists. During the 2003 SARS outbreak, researchers in Singapore detected the virus that causes that disease in patients’ tears. And in Toronto, the risk of infection was higher among health care workers who did not wear eye protection. But because COVID causes severe respiratory problems and other symptoms, and because most eye doctors closed their offices during lockdowns, eyes were overlooked at first, Patel says.

Over the pandemic’s first year and a half, accumulated data have established that about 11 percent of people with COVID develop some kind of eye issue, according to a review of multiple studies. The most common symptom is conjunctivitis, or inflammation of the eye lining. This condition affected nearly 89 percent of people with eye symptoms, researchers in Iran reported in a 2021 meta-analysis that included 8,219 COVID patients across 38 studies.

Other ocular symptoms can include dry eyes, redness, itching, blurry vision, sensitivity to light and the feeling that there is a foreign particle in the eye. People on ventilators often develop a type of eye irritation called chemosis, a swelling or bulging of the eye membranes and eyelids, Patel says. He suspects that as many as one third of people with COVID have some type of eye issue—even if it is just red eyes that do not bother them. And some eye issues are not visible. Patel and his colleagues are working on a study, not yet submitted for publication, that he says will be among the first to report that the virus can cause inflammation in the tissue behind the eyeball.

Eye symptoms can show up early or late in the illness, adds Shahzad Mian, an ophthalmologist at the University of Michigan. He and his colleagues reported ocular signs and symptoms in nearly 10 percent of 400 patients hospitalized in Michigan in March and April 2020.

A person who has COVID can shed the virus through their tears, sometimes long after they have recovered from the illness. One early COVID patient was a 65-year-old woman who travelled from Wuhan to Italy in January 2020 and was soon admitted to a hospital with a cough, sore throat and conjunctivitis in both eyes. Even though her eyes were better by 20 days after she was admitted, researchers detected viral RNA in eye swabs on day 27. In the Lombardy region of Italy, researchers found SARS-CoV-2 on the surface of the eyes in 52 out of 91 patients hospitalized with COVID in the spring of 2020, sometimes even when their nasal swab was negative.

The virus may also able to get into the body through the eyes, studies suggest—either from eye rubbing and the direct transfer of tears or from respiratory droplets that happen to land on the eye. When drops containing SARS-CoV-2 were put into the eyes of rhesus macaques in a 2020 study, the animals got sick. A monkey intervention study cannot reveal whether or how often people get infected through their eyes in real life, but the virus appears to be able to replicate in eye tissue and then make its way into the nasal passages, Mian says. Eye involvement “may be a portal for COVID in addition to being just a symptom,” he says.

As many as 6 percent of people will show symptoms in their eyes before any other signs of COVID, Mian says. Red eyes or irritation could be a sign that someone has the illness, especially if there is a known exposure or other symptoms. “As a parent or as a patient or as a community member, you should be aware that if you have conjunctivitis in this day and age, you want to make sure that it’s not COVID,” he says.

INSIDE THE EARS

Hearing and balance changes can also be signs of SARS-CoV-2 infection, says Zahra Jafari, an audiologist and cognitive neuroscience at the University of Lethbridge in Alberta. In a 2021 meta-analysis, she and her colleagues found dizziness or vertigo in 12 percent of COVID patients, a ringing in the ear known as tinnitus in 4.5 percent and hearing loss in 3 percent. One hypothesis of how SARS-CoV-2 might affect the ears, she says, is that inflammation caused by the virus may directly impact the auditory system. The virus could also invade a barrier between the bloodstream and inner ear.

Confirming those mechanisms has been difficult because the inner ear is notoriously hard to study, Gehrke says. Encased in bone and located deep inside the head, it is inaccessible, and animal models do not always help. Mice are not natural hosts for RNA viruses, so the commonly used lab rodents do not work particularly well as a stand-in for SARS-CoV-2 infection.

To investigate what might be happening inside the ears of people with COVID, Gehrke teamed up with researchers at several other labs to grow human ear tissues using stem cells. With those tissues, the team was then able to show that two types of inner ear cells have the genes for making proteins—including ACE-2 receptors—that allow SARS-CoV-2 to get into cells.

Hair cells, which are important for both hearing and balance, can also be infected by the virus, the researchers reported in Nature in October. The team was able to confirm that inner ear infection with the virus is possible by studying human tissue that had been removed as part of surgeries that were scheduled as treatments for other disorders. The findings are “highly suggestive that, indeed, SARS-CoV-2 patients might have hearing loss associated with virus infection due to infection of the hair cells,” Gehrke says.

Most of the time, both eye and ear symptoms get better on their own, experts say. But research is starting to suggest that, in both cases, COVID-induced symptoms can become long-lasting. Patel knows of two cases in which COVID-patients have lost sensation in their corneas, which can cause those corneas to break down, even with minor trauma. That breakdown can lead to corneal infection, damage and ultimately blindness. Multiple case reports include ear-related symptoms that stick around even after people recover from the illness, Jafari says.

Although damage to sight and hearing still appear to be less common than loss of smell and taste—which can affect 40 percent or more of people with COVID—studies on eyes and ears lend insight into the many and often still mysterious ways that the virus can go to work inside the human body, experts say.

The research also illustrates how intertwined our sensory organs are. Nasal passages butt against Eustachian tubes and eyeballs. “The nerves that allow you to taste, the nerves that allow you to smell, and the nerves that allow you to feel corneal sensation—these are all part of the central nervous system where the brain connects to these different parts,” Patel says. Vision, smell and taste—“these are all connected.”