Background: 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 post-infectious neuropathic pain.

Methods: The study cohort included 18 patients suffering from symptoms suggestive of SFN (Neuropathic pain score DN4 ≥4) appearing after or during SARS-CoV-2 infection and lasting ≥90 days. Patients underwent multimodal SFN evaluation by skin biopsy, quantitative sensory testing (QST), laser evoked potential (LEP) recording and Electrochemical skin conductance (ESC; Sudoscan).

Results: 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 months 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%.

Conclusions: 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 non-invasive exams, are a useful complement to biopsy in the diagnostic process of SFN.