Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID

Abstract

Background and ObjectivesRecovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.MethodsWe analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.ResultsAmong 17 patients (mean age 43.3 years, 69% female, 94% Caucasian, and 19% Latino), 59% had ≥1 test interpretation confirming neuropathy. These included 63% (10/16) of skin biopsies, 17% (2/12) of electrodiagnostic tests and 50% (4/8) of autonomic function tests. One patient was diagnosed with critical illness axonal neuropathy and another with multifocal demyelinating neuropathy 3 weeks after mild COVID, and ≥10 received small-fiber neuropathy diagnoses. Longitudinal improvement averaged 52%, although none reported complete resolution. For treatment, 65% (11/17) received immunotherapies (corticosteroids and/or IV immunoglobulins).DiscussionAmong 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. Various evidence suggested infection-triggered immune dysregulation as a common mechanism.

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

“…Two groups have found evidence of a small fiber neuropathy among those with COVID-19 associated with abnormal autonomic testing. 51, 52…”

“…Two groups have found evidence of a small fiber neuropathy among those with COVID-19 associated with abnormal autonomic testing. 51,52 Autonomic dysfunction could also occur via direct infection of autonomic regulatory regions of the brainstem tone, which are anatomically close to the cribiform plate and the olfactory nerves.…”

“…Skin biopsies suggest small fiber neuropathy among those with COVID-19 associated postural-orthostatic tachycardia syndrome (POTS) and abnormal autonomic testing. 61,62 Similar to preload failure pathophysiology in POTS, autonomic reflexes govern regulation of preload during exercise. 63 Autonomic dysfunction could also occur via infection of autonomic regulatory regions in the brainstem, 64 or through changes in the amygdala evident on longitudinal pre-and post-infection brain MRIs.…”

A Quantum Dot Biomimetic for SARS-CoV-2 to Interrogate Dysregulation of the Neurovascular Unit Relevant to Brain Inflammation

“…Various studies have implicated induction of neuroinflammation as a likely mediator of altered neurologic function associated with COVID-19 neuropathophysiology (2,(73)(74)(75)(76)(77). This idea has gained credence from several human postmortem neuropathologic studies that have not demonstrated widespread infection of either neurons or glia as the basis for long neurologic COVID-19 (31,76,78).…”

SARS-CoV-2 and neurodegenerative diseases: what we know and what we don’t

“…Mild encephalopathies with transient symptoms such as altered consciousness (19.1% of 841 patients) or bradypsychia and disorientation (10.1% of 841 patients) were found to occur rather commonly often accompanied by findings of unspecific T2/FLAIR hyperintensity (35% of 20 patients) and ischemic infarcts (31% of 108 patients) in neuroimaging (Romero-Sanchez et al 2020 ; Mahammedi et al 2020 ; Radmanesh et al 2020 ). Severe COVID-19-associated encephalopathies including ADEM or acute necrotizing encephalopathies and poly(radiculo)neuropathies as GBS or other acute neuropathies (multifocal demyelinating or small fiber polyneuropathy) have also been described in several case reports with an estimated prevalence of 0.1–1% in western countries within 6 weeks of confirmed infection (Mahapure et al 2021 ; Parsons et al 2020 ; Shahali et al 2021 ; Toscano et al 2020 ; Camdessanche et al 2020 ; Hayley and Sun 2021 ; Dixon et al 2020 ; Poyiadji et al 2020 ; Oaklander et al 2022 ). For some entities, a causative relationship to prior SARS-CoV-2 infection is less clear.…”