Abstract 16646: Evidence of Protein Dysregulation in Patients With Post-Acute COVID-19 Syndrome With- and Without Postural Orthostatic Tachycardia Syndrome

Abstract

Introduction: Approximately 30 % of patient with Post-acute COVID-19 Syndrome (PACS) develop postural orthostatic tachycardia syndrome (POTS). The pathophysiological mechanisms behind PACS and associated POTS remain largely unknown. Hypothesis: PACS and POTS-specific phenotype are associated with dysregulation of proteins involved in cardiovascular regulation. Methods: We recruited 20 (19 female) patients with PACS and POTS (age 39±11 years, 18±3 months after SARS-CoV-2 infection) and 22 patients (all female) with PACS without POTS (age 44±11years, 19±3 months after SARS-CoV-2 infection). Head-up TILT test was performed in both groups. Age- and sex matched healthy volunteers (n=21; 20 female, age 43±6 years) without- (n=16) and with (n=5) a history of SARS-Cov-2 infection but without symptoms served as control group. Plasma levels of 700 proteins involved in cardiovascular regulation was analysed using Proximity Extension Assay (Olink® Explore 384 Cardiometabolic Assays I and II). Results: Several proteins were dysregulated both in patients with PACS and POTS (n=206/700, 29%) and in PACS patients without POTS (201/700=29%) compared to healthy controls (figure 1A). Only 13 proteins were uniquely up- and 3 down-regulated in PACS and POTS compared to healthy controls (figure 1B). Gene ontology pathway enrichment analysis revealed upregulation of pathways controlling inflammation, hemostasis, platelet activation and apoptosis in PACS compared to healthy controls (figure 1C). Conclusions: PACS is associated with a substantial protein dysregulation regardless of concomitant POTS up to 18 months after a mild primary SARS-CoV-2 infection. This suggests that PACS-associated POTS exist on a background of protein dysregulation but other pathophysiological mechanisms for PACS-induced POTS need to be established. Whether the dysregulated proteins observed in PACS constitute potential treatment target should be explored.