Does Long COVID After Mild Infection Lead to Small Fiber Neuropathy?

Researchers sought to evaluate patients with long COVID who had been referred for peripheral neuropathy evaluations.

Patients with long COVID-19 often experience prolonged, disabling, small fiber neuropathy (SFN) within 1 month due to immune dysregulation, according to study findings published in Neuroimmunology and Neuroinflammation.

SARS-CoV-2 can lead to long-term disability from COVID and new neurological symptoms, including peripheral neuropathy. Symptoms may overlap with those of small fiber polyneuropathy (SFN), prior studies indicate. The objective of the current study was evaluate patients with long COVID who had been referred for peripheral neuropathy evaluations.

Researchers tracked these patients for a mean 1.4 years, capturing symptoms, exam and objective neurodiagnostic test results, and outcomes. Patients reported symptoms in online surveys and telehealth neuropathy exams.

Of the 17 patients (aged mean 43.3 years, 68.8% women 94.1% White) who had COVID-19 between February 21, 2020, and January 19, 2021, 16 had mild COVID and 1 had severe COVID due to critical care illness and SFN. No patients had conventional neuropathy risks or systemic dysimmunity.

The researchers found that 16.7% of electrodiagnostic studies were abnormal and 62.5% of lower leg skin biopsies confirmed SNF. Half of upper thigh biopsies and autonomic function tests corroborated those results. Initial SFN symptom scores were abnormal (mean 40.7% ideal) and pain scores averaged 4.8/10. Initial neuromuscular exams were a mean 77.0% of ideal, with reduced distal pin and vibration sensation and lack of Achilles reflexes. Two participants had distal muscle weakness and atrophy. Sixteen participants whose condition began in 2020 had more than a year of follow-up.

Corticosteroids treated 6 patients and IV immunoglobulins (IVIg) treated 6 patients. Five patients received doses of 2.0 g/kg/4 weeks and 1 patient received 1.6 g/kg/4 weeks.

Patients who repeatedly received IVIg benefited, the researchers reported. Patients reported a mean 51.8±6.7%, with variations in illness severity, treatment status, and assessment timing.

“This report strengthens evidence linking several idiopathic multisymptom conditions—including SFN and fibromyalgia—with dysimmunity, sometimes incident to infections or vaccinations,” the researchers stated.

Study limitations include bias toward referrals for sensory neuropathy, low power, timing of initial evaluations, and inability to establish causation or magnitude of association.

“Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset,” they concluded.


Oaklander AL, Mills AJ, Kelley M, et al. Peripheral neuropathy evaluations of patients with prolonged long COVID. Neurol Neuroimmunol Neuroinflamm. Published online March 1, 2022. doi: 10.1212/NXI.0000000000001146