Article Text

Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID
  1. Gulfidan Bitirgen1,
  2. Celalettin Korkmaz2,
  3. Adil Zamani2,
  4. Ahmet Ozkagnici1,
  5. Nazmi Zengin1,
  6. Georgios Ponirakis3,
  7. Rayaz A Malik3,4
  1. 1 Department of Ophthalmology, Necmettin Erbakan University Meram Medical Faculty Hospital, Konya, Turkey
  2. 2 Department of Pulmonary Medicine, Necmettin Erbakan University Meram Medical Faculty Hospital, Konya, Turkey
  3. 3 Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
  4. 4 Institute of Cardiovascular Sciences, Cardiac Centre, Faculty of Medical and Human Sciences, University of Manchester and NIHR Clinical Research Facility, Manchester, UK
  1. Correspondence to Dr Gulfidan Bitirgen, Department of Ophthalmology, Necmettin Erbakan University Meram Medical Faculty Hospital, Konya, 42080, Turkey; gbitirgen{at}yahoo.com

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.

  • cornea
  • Covid-19
  • imaging

Data availability statement

The data that support the findings of this study are available from the corresponding author (ORCID: 0000-0002-0509-5649) upon reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Data availability statement

The data that support the findings of this study are available from the corresponding author (ORCID: 0000-0002-0509-5649) upon reasonable request.

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Footnotes

  • Contributors Study concept and design: GB, CK, RAM. Data collection: GB, CK, AZ, AO. Data analysis and interpretation: GB, NZ, GP, RAM. Drafting the manuscript: GB, CK, AZ. Revision of the manuscript: AO, NZ, RAM. Administrative, technical, or material support: AZ, AO, NZ, GP, RAM. Study supervision: RAM.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.