COVID Can Cause Strange Eye and Ear Symptoms

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.

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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.”

4 Ways COVID Leaves Its Mark on the Eye

Authors: Reena MukamalReviewed By Joseph T Nezgoda, MD MBASep. 14, 2021

An analysis of 121 patients dating back to the beginning of the pandemic unveils COVID’s most common effects on the eye. Share this information and remember: Widespread vaccination is key to ending the pandemic American Journal of Ophthalmology

How does COVID reach the eyes?

People respond in different ways to COVID-19 infections. While some people develop mild to severe respiratory problems, others experience no symptoms at all. Pink eye remains the most common sign of COVID in the eyes of children and adults.

Doctors are still learning how COVID affects the eyes. But it’s clear that some people with COVID experience inflammation throughout their body. This inflammation can cause blood clots to form. These clots may travel through the body and reach the veins, arteries and blood vessels of the eye.

COVID’s effects on the retina

The new study suggests that few people with COVID will develop eye problems. But when those problems occur, they can range from mild to vision-threatening. Many of these problems affect the retina — a light-sensing layer of cells in the back of the eye that plays a key role in your vision.

Here are four of the most common eye problems that may develop after COVID infection, according to the new analysis.

1. “Cotton wool” spots

When blood clots prevent nutrients from getting to the retina, the tissue in the retina begins to swell and die. If the doctor examines your eye closely using optical coherence tomography, this area looks white and fluffy like cotton wool (shown in the image above). These spots do not typically affect a person’s vision.

2. Eye stroke (also called retinal artery occlusion)

Blood clots in the arteries of the retina can block the flow of oxygen, causing cells to die. This is known as a retinal artery occlusion, or eye stroke. The most common symptom of an eye stroke is sudden, painless vision loss.

3. Retinal vein occlusion

When a vein in the retina becomes blocked, blood can’t drain out like it should. The buildup of blood raises pressure levels inside the eye, which can cause bleeding, swelling and fluid leaks. People with this complication can develop blurry vision or even sudden, permanent blindness.

4. Retinal hemorrhage

This occurs when blood vessels in the retina start bleeding. It is sometimes caused by a retinal vein occlusion. A hemorrhage can lead to blind spots and gradual or sudden loss of vision.

Am I at risk of eye complications from COVID?

Very few people with COVID will experience serious eye-related complications. But certain people are more likely than others to develop these problems. People with the following conditions are at greatest risk:

When eye problems occur, they tend to develop within 1 to 6 weeks of experiencing COVID symptoms.

These problems have developed in people who were very sick with COVID as well as people who were apparently healthy and lacked symptoms.

Although this is the largest study to date on COVID’s impact on the retina, researchers only examined information from 121 patients. Doctors are continuing to explore how often eye problems affect people with COVID, and how to prevent these conditions.

How to protect your eyes during COVID-19

If you develop symptoms of COVID and notice changes in your vision, schedule an appointment with an ophthalmologist right away.

To protect your eyes and your overall health, be sure to wear a face mask around other people, wash and sanitize your hands frequently and get vaccinated against COVID-19. The potential complications of the disease far outweigh any complications from the vaccine.

Is ‘COVID Eye’ a Thing?

Authors:  Susanne Medeiros;  James G Chelnis, MD Jan. 18, 2022 American Journal of Opthalmology

The British press recently reported that a 9-year-old boy was nearly blinded after developing ‘Covid eye’.  He lost vision in one eye less than a week after testing positive for Covid-19. Physicians determined the boy had developed orbital cellulitis, a bacterial infection in his eye socket.

Cellulitis is serious because if it’s not treated quickly and aggressively, it can lead to blindness. Luckily the boy was treated and made a full recovery.

But does COVID cause cellulitis? There have been a handful of reports of people with COVID who later developed orbital cellulitis. But it’s unclear COVID caused the rare eye infection.

Here’s what ophthalmologists do know. An infection in the blood stream can spread to the eye and cause orbital cellulitis. It’s also possible that those who have recovered from COVID have a weakened immune system and are therefore more susceptible to a new bacterial infection or sinusitis, two conditions that can lead to orbital cellulitis.

Or perhaps small blood clots that form in response to COVID may be to blame? New York ophthalmologist James G. Chelnis, MD, recently treated a patient who developed orbital cellulitis after having COVID. During his COVID infection, the patient developed scattered small blood clots, some that traveled behind the same eye that developed cellulitis.

“Thrombi (blood clots) are like banquets for bacteria,” Dr. Chelnis explained. “It is possible that small emboli are laying the groundwork for infections in the orbit.” 

Whether or not the two conditions are linked, here’s what your ophthalmologist wants you to know about orbital cellulitis.  Because sinus infections are more common in cold weather, cellulitis occurs more in the winter.

Other problems that can lead to cellulitis include:

  • insect bites
  • a skin wound (especially on the face)
  • dental surgery or other surgery of the head and neck
  • sinus infection
  • asthma

It is important to clean any wounds carefully. You also need to follow your doctor or dentist’s instructions for caring for yourself after surgery.

If you think you or your child have cellulitis, call a doctor right away. If it is not treated immediately, cellulitis can cause vision loss or even spread throughout your body.

Cellulitis symptoms include:

4 Ways COVID Leaves Its Mark on the Eye

Authors: Reena MukamalReviewed By Joseph T Nezgoda, MD MBA Sep. 14, 2021

An analysis of 121 patients dating back to the beginning of the pandemic unveils COVID’s most common effects on the eye. Share this information and remember: Widespread vaccination is key to ending the pandemic.

How does COVID reach the eyes?

People respond in different ways to COVID-19 infections. While some people develop mild to severe respiratory problems, others experience no symptoms at all. Pink eye remains the most common sign of COVID in the eyes of children and adults.

Doctors are still learning how COVID affects the eyes. But it’s clear that some people with COVID experience inflammation throughout their body. This inflammation can cause blood clots to form. These clots may travel through the body and reach the veins, arteries and blood vessels of the eye.

COVID’s effects on the retina

The new study suggests that few people with COVID will develop eye problems. But when those problems occur, they can range from mild to vision-threatening. Many of these problems affect the retina — a light-sensing layer of cells in the back of the eye that plays a key role in your vision.

Here are four of the most common eye problems that may develop after COVID infection, according to the new analysis.

1. “Cotton wool” spots

When blood clots prevent nutrients from getting to the retina, the tissue in the retina begins to swell and die. If the doctor examines your eye closely using optical coherence tomography, this area looks white and fluffy like cotton wool (shown in the image above). These spots do not typically affect a person’s vision.

2. Eye stroke (also called retinal artery occlusion)

Blood clots in the arteries of the retina can block the flow of oxygen, causing cells to die. This is known as a retinal artery occlusion, or eye stroke. The most common symptom of an eye stroke is sudden, painless vision loss.

3. Retinal vein occlusion

When a vein in the retina becomes blocked, blood can’t drain out like it should. The buildup of blood raises pressure levels inside the eye, which can cause bleeding, swelling and fluid leaks. People with this complication can develop blurry vision or even sudden, permanent blindness.

4. Retinal hemorrhage

This occurs when blood vessels in the retina start bleeding. It is sometimes caused by a retinal vein occlusion. A hemorrhage can lead to blind spots and gradual or sudden loss of vision.

Am I at risk of eye complications from COVID?

Very few people with COVID will experience serious eye-related complications. But certain people are more likely than others to develop these problems. People with the following conditions are at greatest risk:

When eye problems occur, they tend to develop within 1 to 6 weeks of experiencing COVID symptoms.

These problems have developed in people who were very sick with COVID as well as people who were apparently healthy and lacked symptoms.

Although this is the largest study to date on COVID’s impact on the retina, researchers only examined information from 121 patients. Doctors are continuing to explore how often eye problems affect people with COVID, and how to prevent these conditions.

How to protect your eyes during COVID-19

If you develop symptoms of COVID and notice changes in your vision, schedule an appointment with an ophthalmologist right away.

Ophthalmic Manifestations Of Coronavirus (COVID-19)

Authors: Katherine Hu; Jay Patel; Cole Swiston; Bhupendra C. Patel.

Introduction

Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[1] Initially, there were several reports of eye redness and irritation in COVID-19 patients, both anecdotal and published, supporting conjunctivitis as an ocular manifestation of SARS-CoV-2 infection. Reports continue to emerge on further associations of COVID-19 with uveitic, retinovascular, and neuro-ophthalmic disease.

During the 2003 severe acute respiratory syndrome (SARS) outbreak, a study detected SARS-CoV in tear samples in SARS patients in Singapore.[2] Lack of eye protection was a primary risk factor of SARS-CoV transmission from SARS patients to healthcare workers in Toronto, prompting a concern that respiratory illness could be transmitted through ocular secretions.[3][4] Similar concerns have been raised with SARS-CoV-2, especially among eye care providers and those on the front lines triaging what could be initial symptoms of COVID-19.

As conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19. Indeed, one of the first providers to voice concerns regarding the spread of coronavirus in Chinese patients was Dr. Li Wenliang, MD, an ophthalmologist. He later died from COVID-19 and was believed to have contracted the virus from an asymptomatic glaucoma patient in his clinic.[5]

The authors of this article have attempted to collect the most up-to-date information on ophthalmic manifestations of COVID-19 as a resource for identifying symptoms, providing diagnostic pearls, and mitigating transmission.

Etiology

SARS-CoV-2 is a novel enveloped, positive single-stranded RNA beta coronavirus that causes COVID-19, originally linked to an outbreak in Wuhan of China’s Hubei province.[1] Direct contact with mucous membranes, including the eye, is a suspected route of transmission.

Coronaviruses can cause severe ocular disease in animals, including anterior uveitis, retinitis, vasculitis, and optic neuritis in feline and murine species. However, ocular manifestations in humans are typically mild and rare,[6] although there are increasing numbers of associated ocular findings in patients positive for the COVID-19. There are no described ocular manifestations of Middle East respiratory syndrome (MERS) or SARS, though, as previously stated, SARS-CoV was isolated in ocular secretions.[2] Other coronaviruses have been found to cause viral conjunctivitis in humans.[7]Go to:

Epidemiology

At the time of writing the initial article on April 4, 2020, there were 1,272,953 confirmed cases and 69,428 deaths due to COVID-19 worldwide, according to the World Health Organization (WHO), with 79,332 new cases confirmed in the previous 24 hours. At the time, the Center for Disease Control and Prevention (CDC) had reported 337,278 cases and 9,637 deaths in the United States to that date. On April 16, 2021, just over a year since our initial review, the number of deaths worldwide has crossed the 3 million mark. The severity of the pandemic is emphasized by noting the rate of deaths: it took 8.5 months after the first fatality in China to mark the loss of the first 1 million lives, 3.5 months to reach 2 million, and 3 months for the loss to cross 3 million lives. 

As of December 23, 2021, there have been 51,574,787 confirmed cases of COVID-19 and 809,300 deaths in the United States. Globally, there have been over 276 million confirmed cases of COVID-19 and 5,374,744 deaths reported to the WHO. As of December 23, 2021, a total of 8,649,057,088 vaccine doses have been administered worldwide. The United States has had the most infections to date, followed by India, Brazil, the United Kingdom, Russia, Turkey, and France.

Viral mutations leading to variants of SARS-CoV-2 have been found around the world: the B.1.1.7 in the United Kingdom in early 2020, the B.1.526 in the United States in November 2020, the B.1.525 in the United Kingdom and Nigeria in December 2020, and the B.1.351 in South Africa in late 2020. The Delta variant B.1.617.2 was initially identified in India in December 2020 and rapidly spread through over 60 countries due to a 40-60% increase in transmissibility, becoming the dominant strain globally by August 2021.[8] Most recently, the Omicron variant B.1.1.529 was named a variant of concern in late November 2021 after cases emerged out of Botswana and South Africa with rapid, exponential spread.[9]

Early studies postulated that ocular manifestations of COVID-19 were rare overall. Only 9 (0.8%) out of 1,099 patients from 552 hospitals across 30 provinces in China were reported to have “conjunctival congestion” from December 2019 through January 2020.[10] More recent data, however, have supported a much higher incidence of ocular signs and symptoms. A 2021 meta-analysis by Nasiri et al. reported a pooled prevalence of all ocular manifestations among 7,300 COVID-19 patients as 11.03%, with the most frequent ocular disease being conjunctivitis (88.8%).[11] In the same meta-analysis, dry eye or foreign body sensation (16%), eye redness (13.3%), tearing (12.8%), and itching (12.6%) were among the most frequent symptoms reported. 

A case series reported ocular symptoms in 12 (31.6%) of 38 hospitalized patients with COVID-19 in Hubei province, China.[12] These 12 of 38 patients had conjunctival hyperemia (3 patients), chemosis (7 patients), epiphora (7 patients), or increased secretions (7 patients). Of note is that one patient who had epiphora presented with epiphora as the first symptom of COVID-19. Of those with ocular manifestations, 2 (16.7%) patients had positive results of SARS-CoV-2 on reverse-transcriptase polymerase chain reaction (RT-PCR) by a conjunctival swab, as well as by nasopharyngeal swabs. Only one patient in this study presented with conjunctivitis as the first symptom.[12] The authors noted that patients with ocular symptoms had higher white blood cell and neutrophil counts, C-reactive protein, and higher levels of procalcitonin and lactate dehydrogenase compared to patients without ocular abnormalities. 

Out of 30 hospitalized patients with COVID-19 tested by Xia et al., one patient had conjunctivitis and was also the sole patient in the study to test positive for SARS-CoV-2 in ocular secretions by a conjunctival swab. This patient did not have a severe fever or respiratory symptoms at the time of testing.[13]

Pathophysiology

The pathogenesis and tissue tropism of SARS-CoV-2 relates to the binding of the viral spike protein to its cognate receptor on human host cells— the angiotensin-converting enzyme 2 (ACE-2) receptor. Efficient cell entry requires cleavage by protein transmembrane serine protease 2 (TMPRSS2). ACE-2 is expressed primarily on respiratory mucosal and alveolar epithelial cells and has been identified in other tissues, including the gastrointestinal tract, kidney, vascular endothelial cells, immune cells, and even neurons. Virulence is achieved via direct cellular invasion and death and the induction of widespread cytokine-driven inflammation and vascular leakage.[14] Immune cell and complement debris can also lead to an increased thromboembolic state.

The potential of infection through ocular secretions is currently unknown, and it remains unclear how SARS-CoV-2 accumulates in ocular secretions. Possible theories include direct inoculation of the ocular tissues from respiratory droplets or aerosolized viral particles, migration from the nasopharynx via the nasolacrimal duct, or even hematogenous spread through the lacrimal gland.[6]

Data surrounding the expression of ACE-2 and TMPRSS2 on the ocular surface are mixed. One study demonstrated the expression of both these proteins on the cornea and limbus but observed low levels on the conjunctiva.[15] Lange et al. also found the human conjunctival to have low levels of ACE-2.[16]

A case report from Rome, Italy, isolated SARS-CoV-2 by RT-PCR from conjunctival swabs in a COVID-19 patient with ocular symptoms.[17] Conjunctival swabs were collected from hospital days 3 to 27. Although conjunctivitis was clinically resolved on day 20, the patient had detectable viral SARS-CoV-2 RNA in conjunctival samples on day 21 and subsequently on day 27 after SARS-CoV-2 was negative by nasopharyngeal swab. Because SARS-CoV-2 has not been successfully cultured from human tears or conjunctival swabs, the viability and transmissibility of SARS-CoV-2 in human ocular secretions remains uncertain.[18] Limited reports suggest that tears can be both an early and late source of infection transmission, even after the patient becomes asymptomatic.[17][19]

Using RT-PCR, Azzolini et al. found SARS-CoV-2 present on the ocular surface in 52 of 91 patients with COVID-19 (57.1%).[5] They found that even when the nasopharyngeal swab was negative, the virus was detected on the ocular surface in 10 of 17 patients. It has been postulated that the viral particles in tears may be from the lacrimal gland with diffusion from a systemic load of the virus or from direct contagion from airborne droplets.[5]

History and Physical

The prevalence of ocular manifestations in patients with COVID-19 ranges from 2% to 32%.[20][21][22][23][24][11][25]

Conjunctiva

Patients infected with SARS-CoV-2 can present with acute conjunctivitis symptoms, including eye redness, ocular irritation, eye soreness, foreign body sensation, tearing, mucoid discharge, eyelid swelling, congestion and chemosis. These symptoms have more commonly affected patients with severe systemic symptoms of COVID-19, though they can rarely present as an initial manifestation of the disease.[12] Non-remitting conjunctivitis was found to be the sole manifestation of COVID-19 in five patients with confirmed SARS-CoV-2 infection on nasopharyngeal RT-PCR; these patients never developed fever, general malaise, or respiratory symptoms throughout the course of their illness.[26]

Examination findings include those consistent with mild follicular conjunctivitis, including unilateral or bilateral bulbar conjunctiva injection, follicular reaction of the palpebral conjunctiva, watery discharge, and mild eyelid edema. Bilateral chemosis alone may represent third-spacing in a critically ill patient rather than a true ocular manifestation of the virus. A case report published by Cheema et al. described the first case of keratoconjunctivitis as the presenting manifestation of COVID-19 in North America.[27] The patient’s primary symptoms included eye redness and tearing. The examination was significant for conjunctival injection, the follicular reaction of the palpebral conjunctiva, and corneal findings that developed rapidly over 3 days, including transient pseudodendritic lesions and diffuse subepithelial infiltrates with overlying epithelial defects.

Navel et al. observed a case of severe hemorrhagic conjunctivitis and pseudomembrane formation in a patient with onset 19 days after the beginning of systemic symptoms and 11 days after admission to the intensive care unit.[28]

We saw a 46-year-old male with mild respiratory symptoms and a positive nasopharyngeal test for COVID-19. Five days after the positive test, he developed a hemorrhagic bilateral conjunctivitis with pseudomembrane formation and chemosis. The left eye had been removed some years previously for melanoma. The conjunctival of the socket showed the same hemorrhagic conjunctivitis with chemosis and pseudomembrane formation. He was treated empirically with topical antibiotics and his symptoms resolved in four weeks. He did not develop any other symptoms of COVID-19.

It should be noted that in pediatric patients, COVID-19 has been strongly associated with the Kawasaki-like illness known as multisystem inflammatory syndrome in children (MIS-C). While there have been several ocular manifestations reported in this syndrome (papilledema, iritis, keratitis), the most common ocular manifestation has been conjunctivitis.[29]

Sclera/Episclera

There have been at least two reported cases of episcleritis onset in the setting of COVID-19 infection. Otaif et al. described a 29-year-old male with unilateral episcleritis as the initial presenting symptom of SARS-CoV-2 infection, and Mangana et al. observed nodular episcleritis in a 31-year-old female.[30][31]

Feizi et al. reported two cases of anterior scleritis in patients with COVID-19.[32] The first was a 67-year-old woman with necrotizing anterior scleritis which began 3 weeks after viral symptom onset. The second was a case of sectoral anterior scleritis which was highly responsive to topical and systemic steroids in a 33-year-old male; his ocular symptoms started 2 weeks after the onset of COVID-19.

Anterior Chamber

Beyond the ocular surface, acute anterior uveitis has also been reported both in isolation and in association with COVID-19 related multi-system inflammatory disease.[33][34] Sanjay et al. also reported a case of reactivated idiopathic anterior uveitis post-COVID-19 infection; this patient had remained quiescent for 13 years prior to this episode.[35]

Retina and Choroid

Posterior segment diseases have also been suspected to be associated with COVID-19 infection. These have varied between vascular, inflammatory, and neuronal etiologies. Both ACE-2 and TMPRSS2 are highly expressed in the human retina, and a recent case series of 3 patients discovered S and N COVID-19 proteins by immunofluorescence microscopy within retinal vascular endothelial cells, presumably containing viral particles.[36][37][36]

Both central retinal vein and artery occlusions have been reported in patients without classic systemic vascular risk factors. The hypothesized mechanism includes a complement-induced prothrombic and inflammatory state induced by the virus resulting in endothelial damage and microangiopathic injury. A striking example was reported by Walinjkar et al. with a central retinal vein occlusion (CRVO) in a 17-year-old female with COVID-19.[38] Yahalomi et al. presented a similar case in a previously healthy 33-year-old.[39] Several cases of central retinal artery occlusions (CRAO) have been reported, potentially related to viral-induced endothelial insult and vasculitis.[40][41][42]

Acute macular neuroretinopathy (AMN) and paracentral acute middle maculopathy (PAMM), conditions in which there is ischemia to the deep retinal capillary plexus, have also been observed with COVID, marked by hyperreflective changes at the level of the outer plexiform and inner nuclear layers.[43]

There have been two published case reports on Purtscher-like retinopathy observed in patients with COVID-19. Bottini et al. described a 59-year-old male who presented with multiple bilateral cotton wool spots localized to the posterior pole after a month-long hospitalization for COVID-19 pneumonia associated with multiorgan failure and severe coagulopathy.[44] Rahman and colleagues reported a 58-year-old male who presented with bilateral areas of ill-defined retinal whitening and arteriolar narrowing following a severe COVID-19 infection associated with disseminated intravascular coagulation.[45]

Optical coherence tomography (OCT) showed subclinical hyperreflective lesions at the level of the inner plexiform and ganglion cell layers in 12 adults examined after systemic disease onset; cotton wool spots and microhemorrhages were found on dilated fundus examinations in 4 of these patients.[46] Invernizzi and colleagues found retinal hemorrhages (9.25%), cotton wools spots (7.4%), dilated veins (27.7%), and tortuous vessels (12.9%) in 54 patients with COVID-19 upon screening with fundus photography.[47] These authors also found that retinal vein diameter correlated directly with disease severity, suggesting that this may be a non-invasive parameter to monitor inflammatory response and/or endothelial injury in COVID-19. Lecler et al. described abnormal MRI findings in the posterior pole of 9 patients with COVID-19 consisting of one or several hyperintense nodules in the macular region on FLAIR-weighted images.[48] These lesions were postulated to be either direct inflammatory infiltration of the retina or microangiopathic disease from viral infection.

Various forms of posterior uveitis have been observed following either acute COVID-19 infection or the COVID vaccine. Souza et al. reported a case of unilateral multifocal choroiditis, though it is noted that the temporal relationship of the viral infection could be attributed to chance alone.[49] Goyal et al. published a case of bilateral multifocal choroiditis within one week of the COVID-19 vaccine.[50] Cases of serpiginous and ampiginous choroiditis have also been reported.[51][52][51]

Immune dysregulation due to COVID-19 may contribute to the reactivation of latent herpervirus leading to acute retinal necrosis. This has been reported in two consecutive patients by Soni et al.[53]

Animal model studies have also shown the involvement of the retina with retinal vasculitis [54], retinal degeneration [55], and breakdown of the blood-retinal barrier.[56]

Optic Nerve

A wide variety of neuro-ophthalmologic manifestations have also been found in association with COVID-19, mostly related to demyelinating disease. While the mechanism of these manifestations is unknown, hypotheses include direct neuronal invasion, endothelial cell dysfunction leading to ischemia and coagulopathy, or a widespread inflammatory “cytokine storm” induced by the virus.[57] Optic neuritis has developed in several infected patients, presenting with neuromyelitis optica spectrum disorder and anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies.[58][59][60] Patients presented with subacute vision loss, a relative afferent pupillary defect, pain with eye movements, optic disc edema, and radiographic findings of acute optic neuritis following a COVID-19 infection. There have also been reports of acute optic neuritis following vaccination for COVID-19.[61]

A case of multiple sclerosis following COVID-19 infection was reported by Palao et al. in a 24-year-old patient who presented with right optic neuritis; MRI demonstrated right optic nerve inflammation and supratentorial periventricular demyelinating lesions.[62] These cases suggest that SARS-CoV-2 can either trigger or exacerbate inflammatory and demyelinating disease.

Ophthalmologists may also be called to evaluate for papilledema in SARS-CoV-2 infected patients, as there have been cases of elevated intracranial pressure, both due to widespread inflammation and dural venous sinus thrombosis.[63] As previously mentioned, multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 is also becoming recognized as a unique syndrome similar to Kawasaki disease and has been linked to both optic neuritis and elevated intracranial pressure.[64] Verkuli et al. described a case of a 14-year-old girl with pseudotumor cerebri syndrome associated with MIS-C due to COVID-19 manifesting as a new right abducens palsy, papilledema with disc hemorrhages, and lumbar puncture with an opening pressure of 36 cm H2O.[65]

Extraocular Motility, Cranial Nerves

Cranial nerve III, IV, and VI palsies associated with COVID-19 have been reported in the literature within a few days of fever and cough onset, most without remarkable radiological features.[66][67][68] Ocular cranial neuropathies and binocular diplopia with nerve enhancement on MRI have also been observed in association with post-infectious demyelinating conditions such as Miller Fisher and Guillain Barré syndrome. For example, Dinkin et al. described a 36-year-old male with left mydriasis, ptosis, and limited depression and adduction with concurrent MRI enhancement of the left oculomotor nerve.[69] He was also found to have lower extremity hyporeflexia and ataxia consistent with Miller Fisher syndrome.

Ocular myasthenia gravis has been described as a post-infectious sequela of COVID-19, with authors proposing that antibodies directed against SARS-CoV-2 proteins may cross-react with acetylcholine receptors and similar components at the neuromuscular junction.[70] Huber and colleagues described a 21-year-old patient who presented 4 weeks after COVID-19 infection with fluctuating vertical binocular diplopia and ptosis, treated successfully with intravenous immunoglobulins and oral pyridostigmine.[71]

Pupils

Pupillary changes have also been observed. Several groups have described patients with mydriasis and cholinergic super-sensitivity, indicative of tonic pupils and post-ganglionic parasympathetic pupillary nerve fiber damage.[72][73][74][73]

Nystagmus

Oscillopsia has been reported in several cases of COVID-19 with neurologic involvement. Malayala described a 20-year-old woman who presented with intractable vertigo, nausea, and vomiting with a presumed diagnosis of viral-induced vestibular neuritis secondary to COVID-19.[75] Central vestibular nystagmus has also been described in association with clinical and imaging findings consistent with rhombencephalitis.[76][77]

Visual Cortex

Perhaps the most devastating neuro-ophthalmic complication of severe COVID-19 infection is acute stroke affecting the posterior visual pathways. The incidence of stroke in these patients has been found to be 7.6 times higher than that of patients with influenza and has been occurring in a far younger than average patient population without classic vascular risk factors.[78] These patients may present with homonymous visual field deficits prompting ophthalmologic consultation. Authors at our university recently published a case of bilateral posterior cerebral artery ischemic strokes presenting as a homonymous visual field defect in a 12-year old patient with multisystem inflammatory syndrome related to COVID-19.[79]

Orbit and Ocular Adnexa

While oculoplastic and orbital manifestations of COVID-19 are uncommon, there is growing evidence to link inflammatory and infectious orbital disease to the virus. There have been two reported cases of sinusitis, orbital cellulitis, and intracranial abnormalities in adolescents with COVID-19.[80] It was postulated in this study at SARS-CoV-2 infection resulted in congestion of the upper respiratory tract and increased risk for secondary bacterial infection. This theory was expanded on by Shires et al., who reported a case of bacterial orbital abscess in a patient with COVID-19, with a unique intraoperative finding of highly avascular nasal mucosa and cultures positive for Streptococcus constellatus and Peptonipihilus indolicus, bacteria normally absent in the orbit or upper respiratory mucosa.[81] It is possible that the local microbiologic and immunologic environment was altered due to avascularity induced by thrombosis in the setting of SARS-CoV-2 infection.

There have been a growing number of reports of acute invasive fungal rhino-orbital mucormycosis co-infection with COVID-19. These opportunistic pathogens thrive in the hypoxic respiratory environment induced by SARS-CoV-2, as well as an immunocompromised state induced by high-dose steroids and immunosuppressive therapies. In patients with poorly controlled diabetes, particularly those with diabetic ketoacidosis (DKA), the risk is further increased.[82][83][84] Singh et al. published a systematic review of 101 reported cases of COVID-19 patients with mucormycosis; these patients were predominantly male (79%), 80% of which had diabetes and 15% with concomitant DKA.[85] Corticosteroids had been used in 76% of these patients and nearly 60% of the cases reported rhino-orbital involvement.[85] Another case described a 33-year-old female who presented with orbital compartment syndrome due to concurrent COVID-19 and fulminant mucormycotic infection.[86]

There have also been reports of MRI-proven orbital myositis in two separate COVID-19 patients in the absence of concomitant bacterial infection.[87][88][87] The authors postulated either direct viral orbital invasion or induced autoimmunity as possible mechanisms.

Similar processes have been proposed by Diaz et al., who reported a case of acute dacryoadenitis in a 22-year-old male with positive SARS-CoV-2 antibodies who developed partial ophthalmoplegia.[89] Providers at our university have treated one patient with typical symptoms and signs of dacryoadenitis occurring concurrently with a positive COVID-19 nasopharyngeal test. The patient responded to a slow taper of steroids over six weeks. A recently submitted cases series by our group also highlights a case of biopsy-proven chronic dacryoadenitis in a 57-year-old man with COVID-19, with symptom onset one month following his viral symptoms. Other cases in this series include idiopathic inflammation in an anophthalmic socket.

Lacrimal System

Epiphora has been described as an initial finding in patients with COVID-19.[12] This is thought to be secondary epiphora from inflammation of the conjunctiva. Direct involvement of the nasolacrimal system or the lacrimal sac has not been reported to date. 

Manifestations in Newborn Infants

There have been recent data to support frequent ocular manifestations of SARS-CoV-2 infection in newborn infants. In a study by Perez-Chimal et al. in Mexico, 15 infants were identified with positive RT-PCR nasopharyngeal swabs. All of these newborns exhibited ocular manifestations, most commonly periorbital edema (100%), followed by chemosis and hemorrhagic conjunctivitis (73%) and ciliary injection (53%). Unique findings included 6 infants (40%) with corneal edema, 1 with rubeosis and posterior synechiae, and posterior segment manifestations including retinopathy of prematurity in 3 (20%) infants.[90] Vitreous hemorrhage was observed in 1 full-term baby and subtle cotton wool spots in 2 other newborns.

Evaluation

A thorough history is necessary regarding the onset, duration, and characteristics of symptoms. Anterior segment examination at the slit lamp or bedside can confirm findings of conjunctivitis or episcleritis. Measurement of visual acuity, intraocular pressure, and dilated fundus examination are warranted to rule out potentially more harmful ocular diseases. The clinician should perform a careful examination of pupils and color testing to evaluate patients for evidence of optic neuropathy. Evaluation of extraocular motility may show evidence of nystagmus or cranial neuropathies. Visual field testing can detect and confirm deficits related to stroke.

SARS-CoV-2 can be detected in RT-PCR by sweeping the lower eyelid fornices to collect tears and conjunctival secretions with a virus sampling swab.[13] Additional serum or cerebrospinal fluid testing may be useful to evaluate for inflammatory, autoimmune, or demyelinating entities. Neuroimaging can be valuable in patients presenting with optic neuritis, visual field deficits, cranial neuropathies, or other associated neurologic symptoms.

All patients should be questioned about recent fever, respiratory symptoms, exposure, and travel history to assess the need for further evaluation of COVID-19. 

Treatment / Management

Chen et al. reported gradual symptomatic improvement of COVID-19 conjunctivitis in one patient with administration of ribavirin eye drops.[91] The efficacy of targeted treatment has not been studied. It is unlikely to be of long-term clinical importance in a self-limited viral illness. However, eye care providers should be mindful of trying to decrease possible viral load and potential transmission.[92]

As with other viral infections, COVID-19 conjunctivitis is presumed to be self-limited and can be managed with symptomatic care. In the absence of significant eye pain, decreased vision, or light sensitivity, many patients can be managed remotely with a trial of frequent preservative-free artificial tears, cold compresses, and lubricating ophthalmic ointment. A short course of topical antibiotics can prevent or treat bacterial superinfection based on the patient’s symptoms and risk factors (e.g. contact lens wear).[93] 

On March 18, 2020, the American Academy of Ophthalmology (AAO) urged all ophthalmologists to provide only urgent or emergent care to reduce the risk of SARS-CoV-2 transmission and to conserve disposable medical supplies. Specific criteria are presented below. In the summer of 2020, many centers had begun to resume elective surgeries and consider expanding care on a case-by-case basis based on reopening guidelines from the federal government. 

Although preliminary studies suggest that the risk of viral transmission through ocular secretions is low, large-scale research has not yet been done, and new data is emerging daily. Therefore, healthcare providers are still urged to wear proper protection of the eyes, nose, and mouth when examining patients (see below). Eye care providers and technicians may be more susceptible to infection due to the nature and proximity of the ophthalmic examination.[94] Eye care providers are encouraged to use slit lamp breath shields and should counsel patients to speak as little as possible when sitting at the slit lamp to reduce the risk of virus transmission. Disinfection and sterilization practices should be employed for shared clinic equipment such as tonometers, trial frames, pinhole occluders, B-scan probes, and contact lenses for laser procedures.[2][94] Disposable barrier protection of clinic tools should be used where possible.

Stratification of Ophthalmic Patients for Clinic Visits from early 2020 to December 2020

In the presence of life-threatening infections such as this, ophthalmologists have to achieve a balance between providing ophthalmic care and infection control. Most ophthalmic conditions are not life-threatening. Furthermore, many can be managed with some delay in treatment as they progress relatively slowly (cataracts, glaucoma, ptosis, etc.). However, some conditions like retinal detachments, acute infections (cellulitis, orbital cellulitis), severe inflammation (uveitis), and trauma require more urgent attention. To that end, the following is suggested for the management of ophthalmic patients:

1. All routine ophthalmic patients are delayed until the severity of disease spread reduces as determined by the WHO and the local Chief Medical Officer. These include chronic conditions and routine clinic annual and other follow-ups as well as new patients with chronic conditions like cataracts, ptosis, etc. 

2. New patient referrals are reviewed by the consultant surgeon to determine urgency. If necessary, telephone interviews with the referring doctor and/or the patient are held. 

3. All patients considered for a clinic visit are reviewed for three things: 

  • Presence of fever, cough, or shortness of breath
  • Any foreign travel or travel to an area with a high infection rate within the prior 14 days
  • Any contact with patients who have been diagnosed as having COVID-19

The presence of any of these would be a reason to consider the necessity of seeing and examining the patient more closely. If a patient has two of the three are referred for medical assessment. If a patient with COVID-19 or one with a fever, cough, or shortness of breath needs to be examined, the patient is seen in a separate isolation room. Ideally, only one person (physician, technician, etc.) should be present in the room (as ophthalmic rooms tend to be small) and should wear the full personal protective equipment (PPE): gown, N95 mask, face shield, and gloves. Hands are washed before and after examination for a minimum of 20 seconds with soap and water. Once the ophthalmic examination is completed, the patient is referred for further assessment by the medical team. 

Protection of Medical Workers

Although the 2003 SARS-CoV crisis did not create quite so severe a spread of infection in the United States, it was noted that health care workers (HCW) accounted for about 20% of all patients with infections.[95] Most recent figures show that HCWs make up 9% of Italy’s COVID-19 cases. In the United States, between March 2020 and April 7. 2021, more than 3699 health workers have died from COVID-19 infections with the majority being younger than 60 years of age. As of April 7, 2021, the number of coronavirus cases recorded among healthcare workers in Italy reached 129,873.  Early in the pandemic in Italy, by April 2020, more than 100 health care workers had died from COVID-19 infections, including, more than 60 doctors. Current figures are not available and figures in other countries will continue to increase. 

It is, therefore, vital that front-line medical workers wear proper protection. Secondly, it is important to monitor these health care workers for disease and implement appropriate containment measures. 

A significant number of deaths in the United States were associated with an initial severe shortage of appropriate personal protective equipment for healthcare providers. Even with the availability of appropriate protective equipment, it behooves us to choose the level of protective gear based upon the risk of infection. The following is suggested:

  • Keep the waiting room as empty as possible with available seating spaced at least 6 feet apart.
  • For all patients who have none of the three criteria mentioned above, the medical workers will wear a surgical mask, a face shield, and gloves. Hands are washed before and after every encounter.
  • If a patient is positive for any of the three criteria, the full PPE of gown, face shield, gloves, and the N95 mask are worn. 
  • It has been noted that droplets from sneezes can travel up to 6 meters.[96] To that end, inventive ophthalmic technicians at the Moran Eye Center have developed a slit-lamp shield made by passing two plastic sheets through a laminator without a paper in between and cutting openings for the eyepieces (Fig 1). Others have similarly used old X-ray films when commercially available shields are in short supply. 
  • Conversations are kept to a minimum during the consultation. Ophthalmologists are, by nature, a gregarious lot. Such temptations are to be resisted. 
  • As a shortage of surgical masks has become a reality, some institutions are storing used masks at the end of each day in a container with a view to re-sterilization if necessary. 
  • As many as a quarter of patients being injected under sedation may develop a severe involuntary sneeze.[97][98] This is more common with eyelid injections than with retrobulbar injections. Ophthalmic surgeons should be acutely aware of this to take appropriate precautions during the administration of the local anesthetic. 

Surveillance of Medical Workers

  • In Singapore, health workers reported their temperatures twice a day via an online system: this was eminently sensible as the “walk-by” temperature-testing that was practiced may not be as accurate or complete with staff arriving early, leaving late, etc.[99] As of April 16, 2021, Singapore had had 60,769 infections and only 30 deaths caused by the virus. 
  • All travel outside the state or country should be declared to the medical administration for review. This should still apply in April 2021 as there are recurring hot spots of infection in different states and countries. 
  • All health workers should self-report any symptoms, so appropriate testing may be performed: isolation and contact-tracing would then be undertaken as deemed necessary. 

Sterilization of Equipment

  • The slit-lamp shields are disinfected with 70% ethyl alcohol after each patient; 70% ethyl alcohol has been shown to reduce coronavirus infectivity.[96]
  • Slitlamps, B-scan probes, and any other tools are similarly cleaned with 70% ethyl alcohol.
  • Goldman tonometers are sterilized with a 10% diluted sodium hypochlorite solution, which inactivates coronaviruses.[100]

Differential Diagnosis

Ocular manifestations of COVID-19 have most commonly presented with conjunctivitis otherwise indistinguishable from other viral etiologies. Differential diagnosis includes a broad range of common ocular manifestations of eye redness and increased tearing:

  • Other viral conjunctivitis (e.g., adenovirus)
  • Bacterial conjunctivitis
  • Allergic conjunctivitis
  • Herpes simplex virus keratitis
  • Anterior uveitis
  • Corneal abrasion
  • Foreign body
  • Dry eye syndrome
  • Exposure keratopathy in an intubated patient
  • Chemosis in a critically ill patient

Go to:

Prognosis

Conjunctivitis related to COVID-19 is currently thought to be self-limited. Larger studies and long-term follow-up of patients with other ocular manifestations COVID-19 have yet to be reported. Globally, we are in the grip of grim circumstances with ebbs and flows of infections. With the rather disjointed global response to the infection and unbalanced vaccine administration, the hope that out of the pain joy will spring and new strengths arise from recognition of the weaknesses of administrations around the world is a distant hope.

Complications

Sequelae and complications from demyelinating disease and stroke require management in conjunction with other specialties such as neurology, occupational therapy, and physical medicine and rehabilitation. Ophthalmologists need to be vigilant as we continue to learn of the different ways that COVID-19 may affect the eye and periorbital tissues. 

Deterrence and Patient Education

Prevention strategies are vital to limiting the spread of disease. In addition to physical distancing and practicing good hand-washing hygiene, patients should employ behavioral changes that reduce the direct touching of the eyes and face. These are “soft” suggestions which are mostly ignored now that vaccinations are becoming available and infections in parts of the world are decreasing.

  • Refraining from wearing contact lenses during the outbreak
  • Refraining from applying cosmetics
  • Wearing glasses and sunglasses
  • Changing sheets, pillowcases, and towels regularly

Pearls and Other Issues

  • Ocular shedding of SARS-CoV-2 via tears is a distinct possibility of which ophthalmologists should be aware.
  • Conjunctivitis or tearing can be the first presentation and even sole manifestation in a patient with the COVID-19 infection.
  • Several ocular manifestations of COVID-19 have been observed, including retinovascular disease, uveitis, optic neuropathies, and orbital fungal co-infections.
  • SARS-CoV-2 may trigger or exacerbate inflammatory/demyelinating disease.
  • Patients may present with chemosis in advanced cases (Fig 2) or follicular conjunctivitis (Fig 3).
  • The ocular examination should be performed while wearing gloves and using extension instruments (cotton swabs, etc.) to avoid direct contact with secretions.
  • As many patients who visit the ophthalmic clinic are elderly, many with comorbidities, it is important to screen the need for the visit ahead of time and only see patients who need urgent care. We continue to practice telemedicine for many of these patients. 
  • As advocated in many countries, social distancing means being 6 feet away from others: this is clearly impossible in the clinical world and certainly in the small confines of ophthalmic examination lanes. One way to practice it is to have only one person in the room with the patient.
  • Anecdotally, it has been observed that physicians most at risk of becoming infected include ophthalmologists, otolaryngologists, and anesthesiologists because of the proximity of the examiners to mucosal surfaces.
  • When performing surgery under general anesthesia, it has been recommended that surgeons and other staff do not enter the room for 15 minutes after intubation or extubation. This standard is applied to all general anesthesia cases in many facilities, whether the patient is COVID-19 positive or negative.

Enhancing Healthcare Team Outcomes

Within outpatient, inpatient, and surgical settings, an interprofessional approach is necessary to manage COVID-19 patients and successfully mitigate the spread of disease.

There should be clear communication between hospital administration, provider teams, and clinic support staff regarding expectations for screening patients, wearing personal protective equipment, and utilizing new technologies for telemedicine consultations.

COVID Can Cause Strange Eye and Ear Symptoms

From conjunctivitis to vertigo, coronavirus infections can affect disparate senses

Authors: By Emily Sohn on November 17, 2021

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.”

COVID-19 linked to potentially dangerous eye abnormalities

Authors: by Radiological Society of North America

Researchers using MRI have found significant abnormalities in the eyes of some people with severe COVID-19, according to a study published in the journal Radiology. The study results support the need for eye screening in these patients to provide appropriate treatment and management of potentially severe ophthalmological manifestations of COVID-19.

The COVID-19 pandemic has affected more than 100 million people since it began early in 2020. While the virus primarily attacks the lungs, it has been linked with eye abnormalities like conjunctivitis, also known as pink eye, and retinopathy, a disease of the retina that can result in a loss of vision. Eye abnormalities visible on MRI exams have been reported but there is limited research on the nature and frequency of these abnormalities.

To find out more, the French Society of Neuroradiology (SFNR) initiated a study of 129 patients with severe COVID-19 who underwent brain MRI.

Of the 129 patients, nine (7%) had abnormal MRI findings of the globe, or eyeball. The MRI scans showed one or more nodules in the back part, or posterior pole, of the eyeball. Eight of the nine patients had spent time in the intensive care unit (ICU) for COVID-19.

“We showed that a few patients with severe COVID-19 from the French COVID-19 cohort had one or several nodules of the posterior pole of the globe,” said study lead author Augustin Lecler, M.D., Ph.D., associate professor at the University of Paris and neuroradiologist from the Department of Neuroradiology at the Foundation Adolphe de Rothschild Hospital in Paris. “This is the first time these findings have been described using MRI.”

All nine patients had nodules in the macular region, the area in the back of the eye responsible for our central vision. Eight had nodules in both eyes.

The results suggest that screening should be considered in all patients with severe COVID-19 to detect these nodules. In clinical practice, this screening could include dedicated exploration of the eyes with high-resolution MRI, the researchers said. Additional recommended exams include fundoscopy, which uses a magnifying lens and a light to check the back of the inside of the eye, and optical coherence tomography, a noninvasive test that provides a 3-D picture of the structure of the eye.

Dr. Lecler noted that severe eye problems might largely go unnoticed in the clinic, as COVID-19 patients hospitalized in the ICU are often being treated for much more severe, life-threatening conditions.

“Our study advocates for screening of all patients hospitalized in the ICU for severe COVID-19,” Dr. Lecler said. “We believe those patients should receive specific eye-protective treatments.”

The mechanism behind nodule formation remains unknown, the researchers said, although it could be related to inflammation triggered by the virus. Inadequate drainage of the veins of the eyes, a problem found in patients who spend time in the ICU in the prone position or intubated, may also be a factor. Seven of the nine patients with eye abnormalities in the study had been placed in a prone position in the ICU for an extended time.

The researchers are performing follow-up clinical and MRI examinations in the survivors to monitor the nodules and see if they carry any clinical consequences such as vision loss or visual field impairment.

They are also performing MRI examinations in new patients with severe COVID-19 from the second and third waves of the pandemic, using more comprehensive ophthalmological tests to correlate with the MRI results.

The effects on patients with moderate COVID-19 are currently under investigation.

“We have launched a prospective study with dedicated high-resolution MR images for exploring the eye and orbit in patients with light to moderate COVID,” Dr. Lecler said. “Therefore, we will be able to know whether our findings were specific to severe COVID patients or not.”

The findings support previous research that showed COVID-19 exacts a greater toll in people with existing health problems. Of the nine patients with eye nodules, two had diabetes, six were obese and two had hypertension.

For More Information: https://medicalxpress.com/news/2021-02-covid-linked-potentially-dangerous-eye.html

Severe COVID-19 Linked With Changes in Eyes

Authors: By Ernie Mundell and Robert Preidt HealthDay Reporters WEDNESDAY, Feb. 17, 2021 (HealthDay News)

Severe eye abnormalities have been found in the eyes of some COVID-19 patients, a new study out of France contends.

The findings show the need for eye screening, as well as appropriate treatment and management of potentially serious eye problems in these patients, experts say.

“We showed that a few patients with severe COVID-19 from the French COVID-19 cohort had one or several nodules of the posterior pole of the [eye’s] globe,” explained study lead author Dr. Augustin Lecler, a neuroradiologist at the Foundation Adolphe de Rothschild Hospital in Paris.

One U.S. ophthalmologist unconnected to the study explained that these nodules appeared in a portion of the eye’s globe called the macula.

“The macula is the area of the retina responsible for central vision,” said Dr. Mark Fromer, who practices at Lenox Hill Hospital in New York City. “The retina is easily evaluated by a retina specialist using magnifying lenses at the bed side.”

At this point in time, he said it’s not yet clear whether the eye changes are directly linked to COVID-19 or to its treatment, such as intubating severely ill patients and putting them on a ventilator.

As the Paris team explained, while the coronavirus that causes COVID-19 primarily affects the lungs, it’s been linked with an increased risk for eye conditions such as conjunctivitis (pink eye) and retinopathy, a disease of the retina that can result in vision loss.

There have been reports of eye abnormalities detected on MRI exams of COVID-19 patients, but there’s only been limited investigation into the types and rates of such eye problems.

To learn more, the French Society of Neuroradiology conducted a study of 129 patients with severe COVID-19 who underwent brain MRIs.

Nine (7%) of the patients had one or more nodules in the back part of the eyeball. All had nodules in the macular region, and eight had nodules in both eyes. Eight of the nine patients had COVID-19 so severe that they had to spend time in ICUs.

Ophthalmic Manifestations Of Coronavirus (COVID-19)

Authors: Katherine Hu; Jay Patel; Cole Swiston; Bhupendra C. Patel.Author Information Last Update: May 19, 2021.

Several reports of suspected ocular manifestations of coronavirus disease 2019 (COVID-19) have prompted investigations into ocular signs, symptoms, and transmission. This activity reviews the evaluation and management of ocular manifestations of COVID-19 and highlights the interprofessional team’s role in managing patients with this condition.

Objectives:

  • Summarize the epidemiology of ocular manifestations of COVID-19.
  • Describe the typical presentation of a patient with ocular manifestations of COVID-19.
  • Outline management considerations for patients with ocular manifestations of COVID-19, including key patient counseling on disease transmission prevention.
  • Explain the importance of collaboration and communication among the interprofessional team to improve outcomes for patients affected by COVID-19.

Introduction

Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[1] Initially, there were several reports of eye redness and irritation in COVID-19 patients, both anecdotal and published, suggesting that conjunctivitis is an ocular manifestation of SARS-CoV-2 infection. Reports continue to emerge on further associations of COVID-19 with uveitic, retinovascular, and neuro-ophthalmic disease.

During the 2003 severe acute respiratory syndrome (SARS) outbreak, a study detected SARS-CoV in tear samples in SARS patients in Singapore.[2] Lack of eye protection was a primary risk factor of SARS-CoV transmission from SARS patients to healthcare workers in Toronto, prompting a concern that respiratory illness could be transmitted through ocular secretions.[3][4] Similar concerns have been raised with SARS-CoV-2, especially among eye care providers and those on the front lines triaging what could be initial symptoms of COVID-19.

As conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19. Indeed, one of the first providers to voice concerns regarding the spread of coronavirus in Chinese patients was Dr. Li Wenliang, MD, an ophthalmologist. He later died from COVID-19 and was believed to have contracted the virus from an asymptomatic glaucoma patient in his clinic.

The authors of this article have attempted to collect the most up-to-date information on ophthalmic manifestations of COVID-19 as a resource for identifying symptoms, providing diagnostic pearls, and mitigating transmission.

Etiology

SARS-CoV-2 is a novel enveloped, positive single-stranded RNA beta coronavirus that causes COVID-19, originally linked to an outbreak in Wuhan of China’s Hubei province.[1] Direct contact with mucous membranes, including the eye, is a suspected route of transmission.

Coronaviruses can cause severe ocular disease in animals, including anterior uveitis, retinitis, vasculitis, and optic neuritis in feline and murine species. However, ocular manifestations in humans are typically mild and rare, [5] although there are increasing numbers of associated ocular findings in patients positive for the COVID-19. There are no described ocular manifestations of Middle East respiratory syndrome (MERS) or SARS, though, as previously stated, SARS-CoV was isolated in ocular secretions.[2] Other coronaviruses have been found to cause viral conjunctivitis in humans.[6]

Epidemiology

At the time of writing the initial article on April 4, 2020, there were 1,272,953 confirmed cases and 69,428 deaths due to COVID-19 worldwide, according to the World Health Organization (WHO), with 79,332 new cases confirmed in the previous 24 hours. At the time, the Center for Disease Control and Prevention (CDC) had reported 337,278 cases and 9,637 deaths in the United States to that date. On April 16, 2021, just over a year since our initial review, the number of deaths worldwide has crossed the 3 million mark. The severity of the pandemic is emphasized by noting the rate of deaths: it took 8.5 months after the first fatality in China to mark the loss of the first 1 million lives, 3.5 months to reach 2 million, and 3 months for the loss to cross 3 million lives. 

As of May 17, 2021, there have been over 164 million confirmed cases globally (the real number is, of course, far in excess of this as the number does not include infected individuals who were not tested or asymptomatic cases) and 3,403,722 deaths. India, Iran, and Brazil are currently experiencing the highest number of infections in a 24 hour period ever with new viral strains being discovered in different parts of the world. The United States has had the most infections (33,745,500) and deaths (600,514), followed by India, Brazil, France, Turkey, Russia and the United Kingdom. Increasing infections are currently being seen in Canada, France, Germany, and other countries, necessitating further shutdowns. In the United States, there is an overall uptick in infections as restrictions are relaxed. 

Viral mutations leading to variants of SARS-CoV-2 have been found around the world: the B.1.525 in the United Kingdom and Nigeria in December 2020, the B.1.526in the United States in November 2020, the B.1.1.7 in the United Kingdom in early 202, the B.1.351 in South Africa in late 2020, and the Indian variant in April 2021. 

Early studies postulated that ocular manifestations of COVID-19 were rare overall. Only 9 (0.8%) out of 1,099 patients from 552 hospitals across 30 provinces in China were reported to have “conjunctival congestion” from December 2019 through January 2020.[7] More recent data, however, have supported a much higher incidence of ocular signs and symptoms. A 2021 meta-analysis by Nasiri et al. reported a pooled prevalence of all ocular manifestations among 7,300 COVID-19 patients as 11.03%, with the most frequent ocular disease being conjunctivitis (88.8%).[8] In the same meta-analysis, dry eye or foreign body sensation (16%), eye redness (13.3%), tearing (12.8%), and itching (12.6%) were among the most frequent symptoms reported. 

A case series reported ocular symptoms in 12 (31.6%) of 38 hospitalized patients with COVID-19 in Hubei province, China.[9] These 12 of 38 patients had conjunctival hyperemia (3 patients), chemosis (7 patients), epiphora (7 patients), or increased secretions (7 patients). Of note is that one patient who had epiphora presented with epiphora as the first symptom of COVID-19. Of those with ocular manifestations, 2 (16.7%) patients had positive results of SARS-CoV-2 on reverse-transcriptase polymerase chain reaction (RT-PCR) by a conjunctival swab, as well as by nasopharyngeal swabs. Only one patient in this study presented with conjunctivitis as the first symptom.[9] The authors noted that patients with ocular symptoms had higher white blood cell and neutrophil counts, C-reactive protein, and higher levels of procalcitonin and lactate dehydrogenase compared to patients without ocular abnormalities. 

Out of 30 hospitalized patients with COVID-19 tested by Xia et al., one patient had conjunctivitis and was also the sole patient in the study to test positive for SARS-CoV-2 in ocular secretions by a conjunctival swab. This patient did not have a severe fever or respiratory symptoms at the time of testing.[10]

For More Information: https://www.ncbi.nlm.nih.gov/books/NBK556093/

COVID-19 and Eye: A Review of Ophthalmic Manifestations of COVID-19

Authors: Mrittika Sen 1Santosh G Honavar 1Namrata Sharma 2Mahipal S Sachdev 3 PMID: 33595463 PMCID: PMC7942063 DOI: 10.4103/ijo.IJO_297_21

Abstract

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had health implications of unprecedented magnitude. The infection can range from asymptomatic, mild to life threatening respiratory distress. It can affect almost every organ of the body. Ophthalmologists world over are reporting various manifestations of the infection in the eye. This review was undertaken to help ophthalmologists recognize the possible manifestations and the stage of the viral disease when they commonly appear. Literature search was performed for the publications on ophthalmic manifestations of coronavirus disease-19 (COVID-19) between January 1, 2020 and January 31, 2021. 46 case reports, 8 case series, 11 cross sectional/cohort observational studies, 5 prospective interventional studies, 3 animal models/autopsy studies and 6 reviews/meta-analysis were included. Conjunctivitis is the most common manifestation and can develop at any stage of the disease. Direct effect due to virus, immune mediated tissue damage, activation of the coagulation cascade and prothrombotic state induced by the viral infection, the associated comorbidities and drugs used in the management are responsible for the findings in the eye. The viral ribonucleic acid (RNA) has been isolated from ocular tissues but the role of eye as a route for infection is yet to be substantiated. Ophthalmic manifestations may be the presenting feature of COVID-19 infection or they may develop several weeks after recovery. Ophthalmologists should be aware of the possible associations of ocular diseases with SARS-CoV-2 in order to ask relevant history, look for specific signs, advise appropriate tests and thereby mitigate the spread of infection as well as diagnose and initiate early treatment for life and vision threatening complications.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33595463/