Small fiber neuropathy associated with COVID-19 infection and vaccination: A prospective case-control study

Small fiber neuropathy (SFN) after both COVID-19 infection or vaccination has been reported in sporadic cases, but a detailed description and comparison are missing. We aimed to screen a large cohort of patients complaining of pain and autonomic symptoms after COVID-19 natural infection or vaccination to ascertain the presence of SFN and its correlation with autoimmune diseases. We prospectively recruited for this case-control study 66 patients: 33 developing sensory and autonomic symptoms after a natural COVID-19 infection (P-COVID) and 33 after a mRNA vaccination against COVID-19 (P-VAC). We also used 33 matched healthy controls (HC) collected before 2019 when the COVID-19 virus appeared. Patients underwent neurological examination and clinical scales, an extensive serum screening, and skin biopsy to detect small nerve fiber involvement. Clinical scales showed higher scores for autonomic symptoms in P-COVID patients than in P-VAC patients, but the other scales did not differ. P-COVID and P-VAC patients showed a significant decrease in somatic small nerve fibers compared with HC, whereas autonomic innervation did not differ. SFN was more frequent in P-COVID patients (94%) than in P-VAC patients (79%). Epidermal innervation was correlated with clinical scales for pain and autonomic dysfunctions. Autoimmune abnormalities were frequent in both groups but importantly they were not correlated with SFN. Somatic SFN was frequently found in both P-COVID and P-VAC patients, with a higher incidence in the former group. Spared skin autonomic innervation was spared in both groups although a subtle autonomic involvement in P-COVID patients was suggested by a high COMPASS-31 scale score. SFN was not correlated with autoimmune dysfunctions, although autoimmune diseases were frequent in both groups.