The development and persistence of neurological symptoms following SARS-CoV-2 infection is referred to as “long-haul” syndrome. Here, we aim to study the role of small fiber neuropathy (SFN) underlying neuropathic symptoms associated with COVID-19 infection.

Post COVID-19 “long-haul” syndrome include chronic fatigue, brain fog, sleep disturbance and paraesthesias. These symptoms can overlap with those seen in SFN, which have not been investigated given the recent wave of pandemic and patients who developed new onset of symptoms following infection.

Using retrospective study between May 2020 – May 2021, we screened the skin biopsy database of patients who were referred from the Center of Post-COVID Care at the Mount Sinai Hospital. Thirteen patients were identified and undergone routine nerve conduction studies and electromyography which ruled out evidence of a large fiber neuropathy. Patients were then clinically evaluated and consented for skin punch biopsy. All specimens were processed using PGP9.5 immunostaining for evaluating intraepidermal nerve fiber density (IENFD) to confirm SFN.

We identified 13 patients, 8 women and 5 men (age 38-67 years) with follow-up duration between 8-12 months. All had negative neuropathy blood profile including HbA1c, ANA, B12, TSH, free T4, and serum immunofixation. Three patients had pre-existing but controlled neuropathy risk factors. None had neurological symptoms prior to the SARS-CoV-2 infection. All patients developed new-onset paresthesias within 2 months following infection, with an acute onset in 7 and co-existing autonomic symptoms in 7. Six patients had biopsy-confirmed SFN, all of whom showed both neuropathy symptoms and signs, with 2 showing autonomic dysfunction. Of the remaining 7 patients with negative skin biopsies, 6 showed no clinical neuropathy signs, and 1 exhibited signs with abnormal autonomic function testing.

Our findings support that symptoms of SFN may develop during or shortly after COVID-19 illness. SFN may underlie the paresthesias associated with long-haul post-COVID-19 symptoms.