A Neuroimmunological Axis between systemic autoimmunity and Parkinson's disease following long-COVID: A case series

Long COVID, a multisystemic syndrome following SARS-CoV-2 infection characterized by persistent immune dysregulation, systemic inflammation, and neuroimmune dysfunction, is a significant area of investigation in the neurological sciences. The hypothesis that this pathophysiological state can trigger de novo autoimmune diseases and potentially accelerate underlying neurodegenerative processes is gaining traction. This case series aims to illuminate the potential neuroimmunological link between these conditions by presenting the patients who developed de novo Crohn's disease (CD) and ankylosing spondylitis (AS) following Long COVID and were subsequently diagnosed with post-COVID Parkinson's Disease (PD).

The first case is a 50-year-old female who developed de novo CD six months after COVID-19 pneumonia, managed with the TNF-α inhibitor. Eighteen months later, she presented with parkinsonian motor deficits. The post-COVID PD diagnosis was supported by susceptibility-weighted MRI showing loss of nigrosome-1 and DAT-SPECT revealing a presynaptic dopaminergic deficit. The second case is a 48-year-old female who was diagnosed with de novo AS eight months post-COVID, treated with adalimumab. Twenty-six months later, she developed progressive bradykinesia and rigidity. Neuroimaging confirmed post-COVID PD with corresponding loss of nigrosome-1 and a presynaptic dopaminergic deficit on DAT-SPECT. In both genetically negative cases, dopaminergic therapy led to substantial motor improvement, with Unified Parkinson's Disease Rating Scale (UPDRS) Part IIIscores decreasing from 8 to 3 and 14 to 4, respectively.

This case series proposes a pathogenic cascade wherein SARS-CoV-2 infection acts as an environmental trigger, initiating a Long COVID-associated immune dysregulation that first precipitates a systemic autoimmune disorder. We hypothesize that this sustained inflammatory milieu subsequently accelerates the dysfunction of the dopaminergic system in predisposed individuals, thereby unmasking the clinical phenotype of post-COVID PD. This novel association highlights a potential nexus between virally-induced autoimmunity and subsequent neurodegeneration, offering a new perspective in the field of neuroimmunology.