Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID

Abstract

Background/AimsLong COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID.MethodsForty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density.ResultsThe mean time after the diagnosis of COVID-19 was 3.7±1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (ρ=−0.436; p=0.005, ρ=−0.387; p=0.038, respectively) and CNFL (ρ=−0.404; p=0.010, ρ=−0.412; p=0.026, respectively).ConclusionCorneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.

Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID

“…The hypothesis that some long COVID symptoms reflect underlying small-fiber pathology is supported by research observation of small-fiber loss applying in vivo corneal confocal microscopy to patients with long COVID. 9 As with other post-COVID neurologic illnesses, susceptibility to inflammatory mediators appears essential. Autopsy study of post-COVID patients identified neuritis with perivascular macrophage infiltrates but no viral antigens, implicating inflammatory immune responses rather than direct infection.…”

Subclinical Corneal Nerve Fiber Damage and Immune Cell Activation in Systemic Lupus Erythematosus: A Corneal Confocal Microscopy Study

“…We have pioneered the rapid noninvasive technique of corneal confocal microscopy (CCM) to demonstrate corneal nerve fiber loss in a number of central 14 – 18 and peripheral 19 – 22 neurodegenerative diseases and increased Langerhans cells (LCs) in inflammatory and immune-mediated neuropathies 23 – 27 and long-coronavirus disease (COVID). 28 Moreover, we have shown that CCM has equivalent diagnostic utility to quantitative sensory testing and enhances the diagnosis of small fiber neuropathy. 29 …”

Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology

“…There are small studies which indicate both large ( 68 ) and small ( 69 ) fiber neuropathy in patients following COVID-19, although this may reflect nerve damage associated with severe disease and critical illness ( 70 , 71 ). However, we have recently shown corneal nerve loss and increased dendritic cells in a cohort of patients 12 weeks after relatively mild COVID-19, particularly those with neuropathic and fibromyalgia like symptoms who fulfilled the criteria for long-COVID ( Figure 3 ) ( 72 ).…”