A sizable 10% of patients infected by COVID-19 from SARS-CoV-2 infection develop “long COVID” post-infection and experience often-debilitating symptoms for a protracted period. Studies have suggested that small nerve fiber damage contributes to these lasting symptoms that affect several organ systems, the most prominent being nervous and musculoskeletal.
How does the innervation of the eye fare? A new study used confocal microscopy to quantify sub-basal corneal nerve morphology and dendritic cell (DC) density in patients with and without long COVID. The findings revealed corneal nerve loss and an increase in DC density in patients who have recovered from COVID-19, particularly those with persistent neurological symptoms.
Researchers assessed the data of 40 subjects who recovered from COVID-19 and 30 controls. The mean time after diagnosis of COVID-19 was just under four months, and all had been infected in the previous one to six months. In line with guidelines that define long COVID, patients completed symptom questionnaires at four and 12 weeks post-COVID. CCM was used to assess corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length and various measures of DC density.
The team found that corneal nerve fiber density and length correlated with the total score on the long COVID questionnaire at four and 12 weeks (higher scores = more symptoms). Compared to controls, patients who experienced neurological symptoms four weeks after acute COVID-19 showed nerve fiber loss, along with an increased DC density. At least one neurological symptom was present in 55% and 45% of subjects, four and 12 weeks after the onset of COVID-19, respectively, while at least one symptom was present in 78% and 62% at four and 12 weeks. Though patients without neurological symptoms had similar corneal nerve parameters to controls, they did also have an increased DC density.
“Corneal DC density was increased in COVID-19 patients, comprised of mature DCs in patients with persisting neurological symptoms at four weeks, with an increase in both mature and immature DCs at 12 weeks, providing insights into the evolution of immune activation in COVID-19,” the authors of the study noted. The increase in mature and immature corneal DCs and reduced corneal nerve fiber density is “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.” They note that further studies analyzing the relative change in mature and immature DC density and corneal nerves in COVID-19 patients could examine the contribution of immune and inflammatory pathways to nerve degeneration.
Though infrequently available in most office settings, confocal microscopy “may have clinical utility as a rapid objective ophthalmic test to evaluate patients with long COVID,” the authors concluded.
Bitirgen G, Korkmaz C, Zamani A, et al. Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID. British Journal of Ophthalmology. July 26, 2021. Epub ahead of print.