COVID-19 Infection Linked With Corneal Cellular, Neuroinflammatory Changes

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A study shows significantly reduced posterior stromal keratocyte density and other changes following SARS-CoV-2 infection.

A SARS-CoV-2 infection can be associated with corneal cellular and ultrastructural density changes as a result of inflammation in the cornea, according to research published in Cornea

Researchers selected 30 participants who had previously contracted a SARS-CoV-2 and 41 aged-matched controls. They used In vivo confocal microscopy to examine the corneal cell layers and subbasal nerve fibers cellular and ultrastructural density changes. From these images, researchers analyzed the density of the epithelial cells, anterior stromal keratocyte cells, posterior keratocyte cells, endothelial cells, and dendritic cells and the area of the dendritic cells. Additionally, the nerve fibers and branches of the subbasal nerve plexus were analyzed for density, length, area, and width. 

They found that patients who had experienced a SARS-CoV-2 infection had significantly reduced posterior stromal keratocyte density compared with the control (P =.0006). Upon examination of the dendritic cells, they found significantly higher dendritic cell density in the central cornea (P =.0004) and a significant difference between the previously infected group, and the control group for dendritic cell area (P <.0001). Additionally, hyperreflective round inflammatory cells without dendrites were found following SARS-CoV-2 infection. In all examined areas except for nerve fiber width, the subbasal nerve fiber morphology was significantly altered. All other areas examined showed no significant changes between the groups. 

These results are consistent with previous findings in patients with varying severity of SARS-CoV-2 infection, and the researchers suggest that changes are likely due to inflammation caused by the infection.

“We demonstrated peripheral small nerve fiber damage associated with inflammatory [dendritic cells] even in the absence of severe COVID-19,” study authors explain. “Further studies are needed to investigate the long-term complications of COVID-19-associated corneal neuropathy and its regenerative capacity.”

The limitations of this study include the small sample size and limitation of the population to those who had mild SARS-CoV-2 infection, the lack of a skin biopsy for diagnosis of peripheral neuropathy, and not using standard dry eye disease evaluation with tear film osmolarity on patients. The researchers of this study suggest that future studies should examine the long-term effects of SARS-CoV-2 infection on corneal cellular and ultracellular density.  


Kolkedi Z, Csutak A, Szalai E. Corneal cellular and neuroinflammatory changes after SARS-CoV-2 infection. Cornea. Published online March 18, 2022. doi:10.1097/ICO.0000000000003018