Analysis of microvascular and neurodegenerative complications of mild COVID-19.

PURPOSE: To examine retinal and corneal neurodegenerative and retinal microvascular changes in patients after mild or asymptomatic COVID-19 disease compared to age-matched controls. METHODS: Thirty-five (35) patients after PCR-proven SARS-CoV-2 infection and 28 age-matched controls were enrolled. Swept-source optical coherence tomography (OCT), OCT angiography, and in vivo corneal confocal microscopy were performed in both groups. Corneal subbasal nerve plexus was quantified. Vessel density for superficial (SCP) and deep capillary plexus (DCP) and structural OCT parameters were recorded. RESULTS: Significantly lower nerve branch density (P = 0.0004), nerve fiber area (P = 0.0001), nerve fiber density (P = 0.0009), nerve fiber length (P < 0.0001), and total nerve branch density (P = 0.002) values were observed in patients after COVID-19 compared to healthy controls. VD of the temporal SCP was significantly different between the two groups (P = 0.019). No other SCP and DCP vessel density parameter differed significantly between the two groups. CONCLUSIONS: Our results suggest that peripheral neurodegenerative changes may occur even after mild or asymptomatic SARS-CoV-2 infection. No relevant microvascular changes were seen with OCT angiography and structural OCT parameters did not show any signs of optic neuropathy in post-COVID patients. In vivo confocal microscopy seems to be an important tool in monitoring peripheral neuropathy in patients after COVID-19.

Small fiber neuropathy in the cornea of Covid-19 patients associated with the generation of ocular surface disease.

PURPOSE: To describe the association between Sars-CoV-2 infection and small fiber neuropathy in the cornea identified by in vivo corneal confocal microscopy. METHODS: Twenty-three patients who had overcome COVID-19 were recruited to this observational retrospective study. Forty-six uninfected volunteers were also recruited and studied as a control group. All subjects were examined under in vivo confocal microscopy to obtain images of corneal subbasal nerve fibers in order to study the presence of neuroma-like structures, axonal beadings and dendritic cells. The Ocular Surface Disease Index (OSDI) questionnaire and Schirmer tear test were used as indicators of Dry Eye Disease (DED) and ocular surface pathology. RESULTS: Twenty-one patients (91.31%) presented alterations of the corneal subbasal plexus and corneal tissue consistent with small fiber neuropathy. Images from healthy subjects did not indicate significant nerve fiber or corneal tissue damage. Eight patients reported increased sensations of ocular dryness after COVID-19 infection and had positive DED indicators. Beaded axons were found in 82.60% of cases, mainly in patients reporting ocular irritation symptoms. Neuroma-like images were found in 65.22% patients, more frequently in those with OSDI scores >13. Dendritic cells were found in 69.56% of patients and were more frequent in younger asymptomatic patients. The presence of morphological alterations in patients up to 10 months after recovering from Sars-CoV-2 infection points to the chronic nature of the neuropathy. CONCLUSIONS: Sars-CoV-2 infection may be inducing small fiber neuropathy in the ocular surface, sharing symptomatology and morphological landmarks with DED and diabetic neuropathy.

[First results of clinical diagnostic analysis of post-COVID peripheral neuropathy]. / Pervye rezul'taty kliniko-diagnosticheskogo analiza postkovidnoi perifericheskoi nevropatii.

This analysis of ocular manifestations of the COVID-19 that can occur both in the acute and the post-COVID period focuses on pathological changes associated with hypercoagulation: thrombosis of the central retinal vein, occlusion of the central retinal artery, and decreased peripapillary perfusion. Potential changes in corneal nerve fibers (CNF) associated with coronavirus infection remain poorly understood. Meanwhile, previous studies have shown the possibility of using CNF as biomarkers of polyneuropathy (PNP). PURPOSE: To study clinical and diagnostic features of post-COVID PNP. MATERIAL AND METHODS: We examined 9 female patients aged 32 to 51 years who had suffered an infection caused by SARS-CoV-2 of varying severity. The patients were divided into two groups: the first consisted of 6 patients with clinical manifestations of PNP in the form of neuropathic pain, the second - 3 patients without clinical manifestations. Patients of group 1 underwent comprehensive examination including neurological examination, confocal microscopy of the cornea (in vivo CM), electroneuromyography (ENMG) of the nerves of the upper and lower extremities, quantitative sensory testing in the zone of painful sensations, while patients of group 2 only underwent in vivo CM. RESULTS: All patients of the first group, within 5-40 days after the onset of infection caused by SARS-CoV-2, exhibited symptoms of damage to various parts of the nervous system (peripheral nerves, thoracic spinal roots, trigeminal nerve). The main - and in most cases the only - symptom of the disease was neuropathic pain syndrome. In Guillain-Barré syndrome, for the first time using in vivo CM, the following changes were revealed: enlargement of in Langerhans cells, shortening of CNF and their processes, presence of neuromas. CONCLUSION: The standard neurological examination of patients with post-COVID neuropathy should be supplemented with special diagnostic methods for assessment of structural and functional state of the peripheral nerves. The in vivo CM method is capable of non-invasive assessment of changes in thin CNF and, with accumulation of empirical data, can be included in the algorithm for diagnosing post-COVID PNP.

In Vivo confocal microscopy findings after COVID-19 infection.

PURPOSE: To evaluate clinical and in vivo confocal microscopy (IVCM) findings of a patient who developed multiple unilateral subepithelial stromal opacities following conjunctivitis that developed during a COVID-19 infection. METHODS: A 22-year-old female presented to our clinic with blurred right vision. The history revealed that she had experienced a COVID-19 infection one month ago. Redness and stinging of the right eye had started at the same time and she had been prescribed topical antibiotic drops and ointments. The redness in the right eye had decreased but blurred vision had then developed. RESULTS: Slit lamp examination revealed a normal left eye. Several tiny subepithelial infiltrates without fluorescein staining of the cornea were present in the right eye. The anterior chamber, lens and fundus were bilaterally normal. IVCM revealed irregular corneal epithelial cells with bright borders in addition to scattered inflammatory cells and cell debris in the right eye. There were activated dendritic cells in the subbasal epithelial area with a significant decrease in the subbasal corneal nerve plexus. Clusters of highly reflective cells with an irregular shape were seen in the anterior corneal stroma together with foci of activated keratocytes. The corneal endothelial cell layer was normal. The left eye IVCM findings were all within normal limits. The right eye also showed decreased corneal sensitivity compared to the left. CONCLUSIONS: The possible role of corneal infiltrates as a trigger for COVID-19 could be explained with an immune-mediated mechanism. SARS-CoV-2 can result in decreased corneal sensitivity through corneal nerve involvement. The clinical results of this effect need to be evaluated in larger series.