Corneal nerve fiber morphology following COVID-19 infection in vaccinated and non-vaccinated population – Nature.com

SARS-COV-2 virus infection has been described to have significant impact on nearly all organs in the human body, primarily because of the direct influence of the virus and the extensive inflammatory response it triggers2. Many ophthalmic complications associated with viral infection have been recorded, including conjunctivitis, keratoconjunctivitis, dry eye disease, episcleritis, acute macular neuroretinopathy, venous and arterial retinal vascular occlusion, optic neuritis, intraretinal hemorrhages, uveitis, and endogenous endophthalmitis20,21,22,23. Several studies have reported neurological manifestations associated with COVID-19, including effects on the peripheral nervous system. The SARS-CoV-2 virus has been shown to potentially affect nerves and cause various neurological symptoms24,25,26.

Previous authors reported increased corneal DC density and altered nerve fiber morphology in patients with and without long COVID-19. The difference was more pronounced in post-COVID patients with neurological symptoms at 4weeks7. Our previous study demonstrated peripheral small nerve fiber damage in the cornea associated with inflammatory DCs even after mild COVID-19 disease6.

To date, there is no direct evidence to support the theory that COVID-19 vaccines have neuroprotective effects. However, the vaccines may indirectly provide some neuroprotective benefits by reducing the risk of COVID-19 infection and its potential neurological complications. While the direct neuroprotective effects of COVID-19 vaccines are not yet fully understood, there is some evidence to suggest that vaccination may be associated with a lower risk of cognitive decline and dementia. A study published in the Journal of Alzheimer's Disease found that individuals who received the influenza vaccine had a lower risk of developing dementia compared to those who did not receive the vaccine. It is important to note that the COVID-19 vaccines are a new development, and long-term studies on their potential neuroprotective effects are still ongoing27. However, based on the available evidence, getting vaccinated against COVID-19 is an important step in reducing the risk of infection and potentially reducing the risk of neurological complications.

Besides the benefits of vaccines, several studies reported corneal complications following the administration of the COVID-19 vaccine including corneal graft rejection, herpes zoster ophthalmicus, herpes simplex keratitis, keratolysis and peripheral ulcerative keratitis28. Authors explained their findings with the vaccine-induced immunomodulation and that the increased vascular permeability following vaccination impairs the corneal immune privilege29,30. Significantly higher DC density of DC was observed in the non-vaccinated group compared to the control group. We observed a statistically significant difference in the size of mature DCs but the size of immature DCs did not differ significantly among the 3 groups. The area of mature DCs was the greatest in the non-vaccinated group followed by the vaccinated COVID-19 group, and the difference between the three groups was statistically significant. A previous case report demonstrated a highly elevated mature DC density during COVID-19 infection (237.532.13 cells/mm2) and activated DC clumps around corneal infiltrates as a result of an immune-mediated mechanism31.

The present investigation has certain limitations that should be taken into consideration when interpreting the outcomes. First, due to the low number of cases, we were unable to examine the differences between the vaccinations, and most of the study participants received not only mRNA-based vaccines but also vector-based and attenuated pathogen-containing vaccines or a combination of them. While a larger study population would always be advantageous, our numbers are similar to previously published cross-sectional comparative investigations3,5,6,7. Similarly powered studies support the relevance of our results. Second, since the SARS-CoV-2 virus changes over time causing various disease types with different severities, the included patients might have been affected by multiple virus variants. It should be emphasized that the vaccine is not neuroprotective in the absence of COVID-19 infection. However, in our study, a reduction in neurodegenerative complications was observed in vaccinated patients compared to unvaccinated patients, possibly due to a milder course of infection. Third, while our study identified statistically significant differences in corneal nerve fiber morphology between vaccinated and non-vaccinated individuals after COVID-19, it is crucial to acknowledge the substantial overlap on the graphs. This overlap suggests that despite the observed differences, the distributions of the nerve plexus parameters in the study groups largely coincide. Consequently, the clinical significance of these findings may be limited, as the overlapping spread indicates that individual variations within each group are considerable.

Our study investigated the role of the vaccine against COVID-19 in terms of the subbasal nerve fibers of the cornea, thus indirectly the peripheral nervous system. Our findings showed that corneal nerve fiber density, nerve branch density, nerve fiber length, nerve fiber total branch density, nerve fiber area and width was increased among the vaccinated subjects compared to the unvaccinated COVID-19 group. Corneal dendritic cell density and area were elevated in the unvaccinated group compared to the vaccinated patients within six months after the infection. In summary, our results suggest that SARS-CoV-2 vaccination may have a protective effect against the complications of COVID-19 disease on the corneal subbasal nerve fibers.

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Corneal nerve fiber morphology following COVID-19 infection in vaccinated and non-vaccinated population - Nature.com