Small Fibre Peripheral Alterations Following COVID-19 Detected by Corneal Confocal Microscopy

Abstract

A large spectrum of neurological manifestations has been associated with coronavirus disease 2019 (COVID-19), and recently, the involvement of small fibers has been suggested. This study aims to investigate the involvement of small peripheral nervous fibers in recovered COVID-19 patients using in-vivo corneal confocal microscopy (CCM). Patients recovered from COVID-19 and a control group of healthy subjects underwent in-vivo CCM. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), fiber tortuosity (FT), number of beadings (NBe), and dendritic cells (DC) density were quantified. We enrolled 302 eyes of 151 patients. CNBD and FT were significantly higher (p = 0.0131, p < 0.0001), whereas CNFW and NBe were significantly lower (p = 0.0056, p = 0.0045) in the COVID-19 group compared to controls. Only CNBD and FT resulted significantly correlated to antiviral drugs (increased) and corticosteroids (decreased). No significant relationship with disease severity parameters was found. COVID-19 may induce peripheral neuropathy in small fibers even months after recovery, regardless of systemic conditions and therapy, and CCM may be a useful tool to identify and monitor these morphological changes.

Infectious Neuropathies

“…86 Abnormalities of corneal nerve fibers on confocal microscopy have been reported in patients after COVID-19 compared with controls. 87 Overall, the nature of long COVID and the pathophysiology of the associated neurologic disorders remains uncertain, with limited quantity and quality of evidence. 86 After COVID-19 vaccination, based on Vaccine Safety Datalink data, the US Centers for Disease Control reports a higher risk of GBS with a viral vector vaccine but no increased risk with mRNA vaccines.…”

“…In a retrospective study of 13 patients with post–COVID-19 painful paresthesia, six patients had evidence of small fiber neuropathy on skin biopsy, and two of those six also demonstrated abnormal autonomic testing 86 . Abnormalities of corneal nerve fibers on confocal microscopy have been reported in patients after COVID-19 compared with controls 87 . Overall, the nature of long COVID and the pathophysiology of the associated neurologic disorders remains uncertain, with limited quantity and quality of evidence 86 …”

Corneal Confocal Microscopy as a Quantitative Imaging Biomarker of Diabetic Peripheral Neuropathy: A Review

“…Other studies confirmed and validated the reliability of corneal nerve fiber measurements via ACCMetrics; in particular, the automated quantification of CNFL, CNFD, and CNBD has demonstrated comparable DPN detection ability to manual and semi-automated analysis [ 63 , 130 , 131 ]. Midena et al have recently demonstrated, integrating the ACCMetrics with nerve beading quantification, the presence of corneal neuropathy in subjects previously affected by the COVID-19 disease [ 17 ].…”

“…Our group previously demonstrated how CCM could represent an in vivo, non-invasive, and reproducible diagnostic technique [ 8 ] for the study of corneal morphological alterations not only in diabetic patients but also in other conditions such as post-refractive surgery [ 9 , 10 ], topical chemotherapy in ocular surface squamous neoplasia [ 11 ], vernal keratoconjunctivitis [ 12 ], Wilson disease [ 13 ], oxaliplatin-induced peripheral neuropathy [ 14 ], therapy with epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in patients affected by EGFR-amplified recurrent glioblastoma [ 15 , 16 ], and recently in COVID-19 recovered patients [ 17 ].…”

SARS-CoV-2-Mimicking Pseudoviral Particles Accelerate α-Synuclein Aggregation In Vitro

“…Recovered patients have also been affected by small fiber peripheral neuropathy, similarly to other neuronal degenerative diseases, even months after recovery …”