• Long COVID affects around 1 in 10 people who recover from COVID-19.
• In a recent small study, researchers looked at whether changes to the cornea — the transparent outer layer of the eye — could have links with long COVID.
• The scientists concluded that the loss of nerve fibers and the increase of immune cells in a person’s cornea has links to long COVID. However, larger studies with a greater number of participants are necessary to confirm the results.

In a new study, researchers have identified a link between changes to a person’s cornea and the likelihood of having long COVID.

The researchers hope that in the future, doctors might be able to identify whether a person has long COVID by checking for a loss of nerve fibers and an increase of immune cells in their cornea.

The study appears in the British Journal of Ophthalmology.

Long COVID

COVID-19 is primarily a respiratory disease. According to the Centers for Disease Control and Prevention (CDC), symptoms can range from non-existent, where a person does not know they have contracted the virus, to severe, requiring hospitalization. Over 4.1 million people have died due to COVID-19 globally.

Despite primarily being a respiratory disease, COVID-19 can also affect other parts of the body. A study accepted for publication in the journal BMJ Open found that COVID-19 can also damage various organs.

For the study’s authors, this is one of the key reasons why an estimated 1 in 10 people go on to develop what is known as long COVID, where symptoms continue for weeks or months after the acute phase of COVID-19 has passed.

According to an overview of the syndrome published in the journal Diabetes & Metabolic Syndrome: Clinical Research & Reviews, symptoms of long COVID can include a tight chest, coughing, tiredness, palpitations, feeling breathless, muscle pain, or difficulty focusing.

Researchers have also noted that COVID-19 can also cause neurological symptoms, such as headache, loss of taste or smell, numbness, dizziness, and pain due to problems with the nervous system.

Although they are unsure why this occurs, they think that SARS-CoV-2 — the virus that causes COVID-19 — can transmit directly to a person’s nervous system.

Nerve fiber damage

Another possible underlying mechanism proposed by researchers is small nerve fiber damage.

In previous research, the researchers behind the present study analyzed nerve fiber damage in people’s corneas and linked this to neuropathy and fibromyalgia.

To analyze the cornea, the researchers used a process called corneal confocal microscopy. As well as revealing nerve fiber damage, this also shows the levels of dendritic cells — a type of immune cell — present in the cornea.

The researchers had previously found that increases in these cells had links to diabetic neuropathy and multiple sclerosis.

The researchers wanted to see if damage to a person’s nerve fibers and increases in dendritic cells in the corneas could also be a sign of long COVID.

Speaking to Medical News Today, senior author Dr. Rayaz A. Malik of the Department of Medicine at Weill Cornell Medicine-Qatar in Doha said the significance of the neurological symptoms of long COVID may not be fully appreciated.

“Long [COVID] develops in at least 10% of people after recovery from COVID-19. The primary symptoms during acute [COVID-19] are respiratory and cardiovascular; however, neuropathic symptoms occur and manifest as loss of taste and smell. However, after acute [COVID-19], neuropathic and musculoskeletal symptoms predominate, as captured in the National Institute for Health and Care Excellence [long COVID] questionnaire.

“We believe there is a need for an objective test to identify underlying nerve damage in [long COVID] because many of these symptoms are not being taken seriously. There are parallels between the symptoms of [long COVID] and small fiber neuropathy based on an international consensus I was a part of.

“Over 20 years, we have pioneered an ophthalmic test called corneal confocal microscopy that allows rapid objective quantification of sensory nerve damage in the cornea. This reflects nerve damage in other parts of the body in a wide range of peripheral and central neurodegenerative conditions.

“I have been working with Dr. Bitirgen, an ophthalmologist in Turkey, over almost 10 years where we have used [corneal confocal microscopy] to identify nerve damage and increase immune cells in patients with diabetes, Behçet’s disease, MS, and Fabry disease.”

“It seemed logical that [corneal confocal microscopy] could be a rapid objective test to assess for nerve damage in patients with [long COVID]. The findings of our study now unequivocally show corneal nerve loss in people with [long COVID].”

Controlled study

In the study, the researchers recruited 40 people who had had COVID-19 during the past 1–6 months and 30 people to act as a control.

The researchers asked the 40 people who had recovered from COVID-19 to complete a questionnaire to identify any lingering symptoms at 4 and 12 weeks after receiving a diagnosis of the disease.

The questionnaire covered general symptoms, as well as respiratory, psychological, musculoskeletal, neurological, gastrointestinal, nose, ear, throat, and skin symptoms.

All of the participants underwent corneal confocal microscopy. The researchers then compared the scans of the control group and the participants who had recovered from COVID-19.

Link to neurological symptoms?

The researchers found that the participants who reported neurological symptoms at 4 weeks had more nerve fiber damage and increased dendritic cells than the control participants.

Participants who had recovered from COVID-19 but did not report lingering neurological symptoms had similar nerve fibers to the control group. However, the researchers found that they also had increased levels of dendritic cells.

More generally, the researchers found a strong correlation between the results of the questionnaires that suggested long COVID and corneal nerve fiber damage.

According to Dr. Malik, their findings clarify the need for further research to confirm and expand the study.

Speaking to MNT, Dr. Malik said, “[l]arger studies are required to confirm our initial findings, which show definite corneal nerve damage in patients with long [COVID] and an ongoing immune response long after these patients have ‘recovered’ from acute [COVID-19]. We also need to perform longitudinal studies to see the evolution of this condition.”

Dr. Malik told MNT that the findings could be crucial in ensuring recognition of long COVID as a legitimate illness and ensuring that people experiencing the syndrome get the support they need.

“Clinicians need to utilize the NICE questionnaire or have a rapid test to identify [long COVID]. The only way that the medical profession will take long [COVID] seriously is if they have an objective test to confirm or refute [its diagnosis]. We believe [corneal confocal microscopy] provides a rapid and non-invasive way to do this.”

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