This cross-sectional study examined central sensitization (CS) prevalence and its associations with autonomic symptom burden, cerebral blood flow, neuroinflammation (IL-6), and small-fiber neuropathy in 169 consecutive Long COVID patients referred for orthostatic intolerance evaluation.
CS was present in 81% of patients. Those with CS had greater orthostatic cerebral blood flow velocity decline (-25.53% vs. -22.09%, p=0.038), higher IL-6 levels (p=0.041), and significantly worse autonomic, sensory, and global health symptom scores (all p<0.001). Autonomic failure rates (≈85%) and abnormal skin biopsy findings (≈51%) were similar between CS and non-CS groups.
Single-center referral cohort limits generalizability; cross-sectional design prevents causal inference between CS, hypoperfusion, and neuroinflammation; CS was measured via self-report inventory (Central Sensitization Inventory), not a biological gold standard.
Screen Long COVID patients with orthostatic intolerance for central sensitization — it is present in 4 out of 5 and linked to worse multisystem symptom burden, greater cerebral hypoperfusion, and elevated IL-6. Recognizing CS as a distinct contributor may help target management beyond autonomic dysfunction alone.
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