The punishing symptoms of long COVID are largely invisible to the eye, but new research suggests one of the hallmarks of the disease could literally be staring us in the face.

Long COVID refers to a staggering range of debilitating symptoms that up to 30 percent of patients endure long after recovering from acute SARS-CoV-2 infection, including brain fog, headaches, fatigue, loss of taste and/or smell, and more.

Many of these discomforts aren't always obvious on the outside, but according to a new study, long COVID might actually be detectable in the eyes of patients, in the form of nerve damage that can be seen in the cornea.

The cornea is a transparent dome that forms the front surface of the eye, covering the iris and pupil.

Nerve damage in the cornea can be detected by a non-invasive laser technique called corneal confocal microscopy (CCM), which has been used by researchers to identify corneal abnormalities linked to a range of diseases, such as nerve damage from diabetes, multiple sclerosis, and fibromyalgia.

Here, the team used the same technique to see if CCM could identify corneal nerve damage and increased dendritic cells (DCs, a type of immune system cell) in cases of long COVID. They compared the results of 40 patients with previous COVID-19 infections against CCM observations of 30 healthy individuals who never had the disease.

According to the researchers, CCM can be used to help indicate long COVID, with corneal scans of a subset of the COVID-19 group (patients who reported ongoing neurological symptoms after recovery from the virus) showing greater corneal nerve fiber damage and loss, along with higher counts of dendritic cells, than healthy participants.

"To the best of our knowledge, this is the first study reporting corneal nerve loss and an increase in DC density in patients who have recovered from COVID-19, especially in subjects with persisting symptoms consistent with long COVID," the researchers, led by first author Gulfidan Bitirgen from Necmettin Erbakan University in Turkey, write in their paper.

While this is only a small study – and an observational study at that, which can't confirm that COVID-19 actually caused these patients' corneal abnormalities – the links here nonetheless amount to further evidence of how SARS-CoV-2 infection may contribute to neurological and neuropathic problems.

This could be due to potential disruptions to healthy nerve fiber development, leading to an increase in dendritic cells summoned as part of our immune response.

"These findings are consistent with an innate immune and inflammatory process characterized by the migration and accumulation of DCs in the central cornea in a number of immune mediated and inflammatory conditions," the team explains.

"Further study of the relative change in mature and immature DC density and corneal nerves in COVID-19 patients over time may provide insights into the contribution of immune and inflammatory pathways to nerve degeneration."

According to the results, the patients with more severe cases of COVID-19 tended to exhibit greater corneal nerve damage, so it's possible the eye abnormalities shown here all stem from the way the disease presents in patients, the researchers suggest.

As the team acknowledges, more research with much larger cohorts is needed to pursue these early leads, but for now it's yet another example of how closely eye health is linked to our wider health, which is why techniques like CCM could have great promise as future diagnostic aids.

"Corneal confocal microscopy may have clinical utility as a rapid objective ophthalmic test to evaluate patients with long COVID," the researchers say.

The findings are reported in British Journal of Ophthalmology.