Comparative Analysis of Circulating Cytokines and Adrenergic Autoantibodies in Postural Orthostatic Tachycardia Syndrome, Postacute Sequelae of SARS-CoV-2, and Healthy Controls

Postural orthostatic tachycardia syndrome (POTS) is increasingly recognized after SARS-CoV-2 infection. We compared autonomic phenotype, functional impact, and circulating immune markers in POTS, postacute sequelae of COVID-19 (PASC), and healthy controls. In this cross-sectional study (August 2021 to December 2022), we recruited patients with POTS (n=24) or PASC (n=24) and healthy controls (n=19). Participants underwent 10-minute active stand testing, 24-hour Holter monitoring, serum cytokine, and adrenergic autoantibody assays (cell-based activation). Patient-reported outcome measures were collected via secure electronic link. The study included 67 participants (mean age, 32.4±8.9 years; 71% women). Compared with controls and participants with PASC, participants with POTS demonstrated significantly higher orthostatic tachycardia (active stand heart rate change from supine to standing, 46.3±14.0 bpm versus 12.7±6.6 bpm in controls and 34.6±13.7 bpm in PASC; <0.001; POTS versus PASC =0.005). Among participants with PASC, 62.5% met formal POTS criteria. Cytokine analysis revealed lower interleukin-2 and higher interleukin-8 levels in POTS versus controls, with POTS cases showing elevated tumor necrosis factor-α compared with those without POTS. Autoantibody activation measures did not differ significantly among groups, and multivariate biomarker models lacked predictive utility for POTS diagnosis. Patient-reported outcome measures indicated greater fatigue, orthostatic intolerance, and autonomic symptom burden and reduced health-related quality of life in POTS and PASC groups compared with controls. POTS and PASC exhibit overlapping autonomic symptomology and profound functional impairment. Alterations in cytokines suggest a possible cytokine-linked or compartmentalized immune contribution, but cytokine and autoantibody measures alone do not predict POTS. Routine autonomic assessment in persistent postviral illness and larger longitudinal, multimodal studies are warranted. Australian New Zealand Clinical Trial Registry; ACTRN: 12621000476831.