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

Abstract

Background/aims: Long 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.

Methods: Forty 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.

Results: The 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).

Conclusion: Corneal 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.

Keywords: Covid-19; cornea; imaging.

Figure 1

Representative corneal confocal microscopic images of the central corneal sub-basal nerve plexus in a healthy control participant (A), and in COVID-19 patients with (B) and without (C) long COVID.

Figure 2

Corneal nerve fibre parameters and dendritic cell density in healthy control participants and patients with and without neurological symptoms 4 weeks after the initial diagnosis of COVID-19. Error bars indicate mean (SD) for corneal nerve fibre density, nerve branch density and nerve fibre length, and median (IQR) for dendritic cell density.