Cervicothoracic Mechanical Constraint of the Vagus Nerve as a Unifying Causal Mechanism in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

Post-acute sequelae of SARS-CoV-2 infection (PASC) manifests as persistent multisystem dysfunction with marked clinical heterogeneity. Although immune dysregulation, endothelial injury, mitochondrial impairment, and gut microbiome alteration are consistently documented, prevailing models treat these abnormalities as parallel downstream effects rather than identifying a central sustaining driver. This manuscript proposes that PASC is primarily driven by mechanically mediated disruption of vagal-autonomic signaling arising from posture-dependent constraint at the cervicothoracic junction. SARS-CoV-2–induced neuroinflammation and fibro-inflammatory remodeling are hypothesized to create perineural vulnerability, predisposing to focal connective-tissue adhesions and chronic mechanical compression. Anatomical variability in vagal pathways and constraint loci is predicted to generate distinct symptom phenotypes. A falsifiable experimental framework incorporating mechanical provocation, metabolic stress testing, sham controls, and a standardized standing mechanical release maneuver is presented to test mechanotransductive reversibility and sustained autonomic recalibration.