BACKGROUND: 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.
METHODS: 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.
RESULTS: 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. P P
CONCLUSIONS: 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.
REGISTRATION: Australian New Zealand Clinical Trial Registry; ACTRN: 12621000476831.
