Small Fiber Neuropathy in Long COVID: A Cohort Study with Multimodal Assessment and Follow-Up

Given the increasing number of patients suffering from pain associated with dysautonomic symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we aimed to estimate the occurrence of small fiber neuropathy (SFN) in a cohort of long coronavirus disease 19 (COVID-19) patients reporting postinfectious neuropathic pain.

The study cohort included 18 patients suffering from neuropathic pain (neuropathic pain score DN4 ≥4) appearing after or during SARS-CoV-2 infection and lasting ≥90 days; presenting normal nerve conduction studies excluding large fiber damage. Patients underwent multimodal SFN evaluation by skin biopsy, quantitative sensory testing (QST), laser evoked potential (LEP) recording and electrochemical skin conductance (ESC; Sudoscan).

Out of 18 patients, 17 were analyzed. Participants' ages averaged 44 ± 9 years, with 94% females. Fourteen (82%) had abnormal skin biopsy results. Notably, 12/17 (70%) patients presented with autonomic complaints, all of whom had abnormal skin biopsy results. At 6-month follow-up, 10/17 patients reported a subjective improvement in pain and/or dysautonomia with or without symptomatic pharmacological or non-pharmacological treatment. In our cohort, QST showed the highest sensibility (79%) and specificity (67%), followed by LEP (sensibility 71%, specificity 67%). ESC showed poor reliability in the screening of SFN with a sensibility of 7% and specificity of 50%.

The results of our study suggest that SFN may develop during or shortly after SARS-CoV-2 infection, provoking disabling sensory and dysautonomic symptoms that tend to persist for more than 6 months. Furthermore, our findings imply that noninvasive exams are a useful complement to biopsy in the diagnostic process of SFN.