Universitätsklinikum Würzburg: Nicht nur eine Reaktion, sondern die Ursache

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

Objectives Report 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. Methods A 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. Results Sixteen 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. Discussion Here 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Yale University IRB I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript

Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome - Journal of Translational Medicine

Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms. Methods The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 healthy controls (HC). The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and HC, as well as, analyze the relationship of these symptoms with cognition and fatigue. Results Statistically significant differences were found between groups in heart rate using the Kruskal–Wallis test (H), with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance. Conclusions Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.