In this case-control study, our primary objective was to detect small fiber neuropathy (SFN) among patients who experienced sensory symptoms and pain following the acute phase of COVID-19. Additionally, we sought to investigate potential risk factors associated with the development of SFN and to delve into the mechanisms contributing to the occurrence of post-COVID-19 pain.

To definitely diagnose SFN, we collected clinical data and investigated quantitative sensory testing (QST) and skin biopsy in 26 selected patients with painful post COVID-19 conditions. We also screened 100 previously ill COVID-19 survivors, selecting 30 control participants without any post COVID-19 neurological symptoms and 33 patients with painless post COVID-19 symptoms. Then, we compared the main demographic and clinical variables between groups.

Among the 26 patients with painful post-COVID-19 conditions, 12 exhibited clinical sensory signs and abnormalities in skin biopsy and/or QST results, consistent with a diagnosis of SFN. In our patients, demographic and clinical data (including COVID-19 severity) were comparable to those of previously ill COVID-19 survivors without neurological symptoms and to patients with painless post COVID-19 symptoms. The most frequent QST sensory profile among patients with SFN was mechanical hyperalgesia.

Our study showed that SFN is relatively common in patients suffering from painful post COVID-19 condition; in our patients, however, this specific post COVID-19 complication was unrelated to demographic and clinical variables related to COVID-19, highlighting the need to screen this population for the presence of SFN, regardless of COVID-19 severity or specific risk factors. Moreover QST data suggests  that pain might predominantly reflect central sensitization phenomena.