Small fibre neuropathy frequently underlies the painful long-COVID syndrome

Pietro Falco; Daniel Litewczuk; Giulia Di Stefano; Eleonora Galosi; Caterina Leone; Gianfranco De Stefano; Giuseppe Di Pietro; Lorenzo Tramontana; Maria Rosa Ciardi; Patrizia Pasculli; Maria Antonella Zingaropoli; Lars Arendt-Nielsen; Andrea Truini

doi:10.1097/j.pain.0000000000003259

Small fibre neuropathy frequently underlies the painful long-COVID syndrome

Pain. 2024 May 7. doi: 10.1097/j.pain.0000000000003259. Online ahead of print.

Authors

Affiliations

¹ Department of Human Neuroscience, Sapienza University, Rome, Italy.
² Department of Medicine, Infectious Diseases, Sapienza University, Rome, Italy.
³ Centre for Neuroplasticity and Pain, SMI, School of Medicine, Aalborg University, Aalborg, Denmark.
⁴ Department of Gastroenterology and Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark.
⁵ Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, Aalborg, Denmark.

PMID: 38723183
DOI: 10.1097/j.pain.0000000000003259

Abstract

Approximately 10% to 20% of individuals with previous SARS-CoV-2 infection may develop long-COVID syndrome, characterized by various physical and mental health issues, including pain. Previous studies suggested an association between small fibre neuropathy and pain in long-COVID cases. In this case-control study, our aim was to identify small fibre neuropathy in patients experiencing painful long-COVID syndrome. Clinical data, quantitative sensory testing, and skin biopsies were collected from 26 selected patients with painful long-COVID syndrome. We also examined 100 individuals with past COVID-19 infection, selecting 33 patients with painless long-COVID syndrome, characterized mainly by symptoms such as brain fog and fatigue, and 30 asymptomatic post-COVID-19 controls. Demographic and clinical variables were compared among these groups. Among the 26 patients with painful long-COVID syndrome, 12 had skin biopsy and/or quantitative sensory testing abnormalities compatible with small fibre neuropathy. Demographic and clinical data did not differ across patients with small fibre neuropathy, patients with painless long-COVID syndrome, and asymptomatic post-COVID-19 controls. This case-control study showed that approximately 50% of patients experiencing painful long-COVID syndrome had small fibre neuropathy. However, in our patient cohort, this specific post-COVID-19 complication was unrelated to demographic and COVID-19 clinical variables. Approximately half of our sample of patients with painful long-COVID symptoms met diagnostic criteria for small fibre neuropathy.