Patients with long COVID-19 have corneal small nerve fiber damage and increased dendritic cells (DCs), investigators found in a study published in British Journal of Ophthalmology

An estimated 80% of patients who recover from COVID-19 continue to have at least 1 symptom, sign, or abnormal laboratory parameter, beyond 2 weeks after initial diagnosis and at least 10% will go on to develop long COVID.  The researchers used corneal confocal microscopy (CCM) to identify whether small nerve fiber damage is a biomarker of long COVID.

The study included 40 patients who had contracted COVID 1 to 6 months previously and 30 control individuals in the study. They reviewed the COVID-19 patients’ blood test results and identified persisting symptoms at 4- and 12-weeks after diagnosis using the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia (FM-Q) questionnaires. The researchers used CCM to compare subbasal corneal nerve morphology and DC density in patients with and without long COVID. They manually quantified corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and DC density.


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The 55% of COVID patients who had neurological symptoms at 4 weeks following diagnosis tended to have lower CNFD (mean difference -4.85 (1.88); P =.032), CNBD (mean difference -14.62; P =.020), and CNFL (mean difference -3.35; P =.012) compared with the control individuals. They had increased total (median 35.1 vs 12.7) cells/mm2; P =.046) and mature (median 7.3 vs 0 cells/mm2; P =.003) DC densities compared with the control individuals.

Patients without neurological symptoms had higher total median 53.5 vs 12.7 cells/mm2; P =.003), mature (median 7.3 vs 0 cells/mm2; P =.010) and immature (median 33.5 vs 12.7) cells/mm2; P =.007) DC densities, compared with control individuals.

Patients with neurological symptoms at 12 weeks had a lower CNFD (mean difference -6.94; P =.008), CNBD (mean difference -16.40; P =.031) and CNFL (mean difference -4.51; P =.004), and higher total (median 59.6 vs 12.7 cells/mm2; P =.016), mature (median 8.3 vs 0 cells/mm2; P =.001), and immature (median 41.2 vs 12.7 cells/mm2; P =.039) DC densities, compared with control individuals. CNFD (mean difference -7.78; P =.008) and CNFL (mean difference -4.80; P =.006) were lower in patients with neurological symptoms compared with those who did not.

COVID patients with long COVID had significantly higher musculoskeletal symptoms (FM-Q) (median 11.0 vs 2.0, respectively; P =.001) than those without long COVID.

Limitations of the study include the use of questionnaires to define the severity of neurological symptoms instead of more objective measures and lack of assessment of ocular surface symptoms and corneal sensitivity.

Reference

Bitirgen G, Korkmaz C, Zamani A, et al. Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID. Br J Ophthalmol. 2021;0:1-7. doi:10.1136/bjophthalmol-2021-319450