Small Fiber Neuropathy after COVID-19: A Key to Long COVID

ObjectivesReport a case series of new onset small fiber neuropathy (SFN) after COVID-19 treated with intravenous immunoglobulin (IVIG). SFN is a critical objective finding in long COVID and amenable to treatment. MethodsA retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We documented demographics, symptoms, treatments, diagnostics, and clinical response to treatment. ResultsSixteen patients were diagnosed with length dependent or independent SFN on skin biopsy (median age 47, 75% female, 75% Caucasian). Among the nine patients tested for autoantibodies, six were positive for either trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor 3 (FGFR3). Eight patients underwent treatment with IVIG and experience significant clinical improvement in their neuropathic symptoms. 92% of patients reported post-exertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and six patients underwent invasive cardiopulmonary exercise testing (iCPET), which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. DiscussionHere we present preliminary evidence that SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating post-infectious small fiber neuropathy.