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Objective: To describe corneal confocal microscopy findings in patients with long COVID-19 with persistent symptoms over 20 months after SARS-CoV-2 infection. Design: A descriptive cross-sectional study that included a total of 88 patients; 60 patients with Long COVID-19 and 28 controls. Long COVID-19 diagnosis was established according to the World Health Organization criteria. Corneal confocal microscopy using a Heidelberg Retina Tomograph II (Heidelberg Engineering, Heidelberg, Germany) was performed to evaluate sub-basal nerve plexus morphology (corneal nerve fiber density, nerve fiber length, nerve branch density, nerve fiber total branch density, nerve fiber area, and nerve fiber width). Dendritic cell density and area, along with microneuromas and other morphological changes of the nerve fibers were recorded. Results: Long COVID-19 patients presented with reduced corneal nerve density and branch density as well as shorter corneal nerves compared to the control group. Additionally, Long COVID-19 patients showed an increased density of dendritic cells also with a greater area than that found in the control group of patients without systemic diseases. Microneuromas were detected in 15% of Long COVID-19 patients. Conclusions: Long COVID-19 patients exhibited altered corneal nerve parameters and increased DC density over 20 months after acute SARS-CoV-2 infection. These findings are consistent with a neuroinflammatory condition hypothesized to be present in patients with Long COVID-19, highlighting the potential role of corneal confocal microscopy as a promising noninvasive technique for the study of patients with Long COVID-19.

In vivo corneal confocal microscopy (IVCM) is a non-invasive ophthalmic imaging technique that provides images of the cornea at the cellular level. Despite the uses in ocular surface pathologies, in the last decades IVCM has been used to provide more knowledge in refractive surgery wound healing, in neuropathies diagnosis, etc. The observation of the corneal cells, both normal and inflammatory, and the possibility of quantification of the corneal nerve density with manual or automated tools, makes IVCM have a significant potential to improve the diagnosis and prognosis in several systemic and corneal conditions.