Clinical significance of endothelin-1 and angiotensin-2 levels in patients with post-COVID syndrome according to the timing of rehabilitation therapy

   Introduction. Post-COVID syndrome (PCS) leads to multiorgan dysfunction, the primary pathophysiological basis of which is considered to be endothelial dysfunction – a state of imbalance among vasoactive and angiogenic mediators.

   Aim. To evaluate the clinical relevance of endothelin-1 (EDN1) and angiotensin-2 (ANG-2) levels in PCS patients in relation to the timing of enrollment in rehabilitation treatment.

   Materials and methods. The study included 190 patients diagnosed with PCS and 30 healthy controls with no prior history of COVID-19. Assessments encompassed clinical, functional, and laboratory evaluations, including enzyme-linked immunosorbent assay (ELISA) for serum levels of ANG-2, EDN1, bactericidal/permeability-increasing protein (BPI), and C-reactive protein (CRP). Pulmonary function was assessed by spirometry. Physical performance was measured using the 6-minute step test (6MST), dyspnea severity via the Baseline Dyspnea Index (BDI). Fatigue was assessed using the Fatigue Assessment Scale (FAS), and health-related quality of life by the SF-36 questionnaire.

   Results. Patients were stratified into four groups based on PCS duration: Group I (<6 months), Group II (6–12 months), Group III (12–24 months), and Group IV (>24 months). Cardiovascular comorbidities predominated in Groups I and II, whereas bronchial asthma and chronic bronchitis were more common in Groups III and IV. Notably, 11.5 % of patients developed respiratory diseases de novo after COVID-19. ANG-2 levels were elevated across all PCS groups compared to controls. EDN1 concentrations were highest in Group I (52.3 [33.3; 62.5] pg/mL) versus controls (44.4 [39.81; 47.22] pg/mL) and showed a progressive decline with longer PCS duration: Group II – 39.4 [26.4; 50.0] pg/mL; Group III – 23.2 [16.0; 40.7] pg/mL; Group IV – 18.7 [16.5; 21.7] pg/mL. FAS and SF-36 scores revealed persistent chronic fatigue and reduced quality of life – both physical and mental – among PCS patients.

   Conclusion. For up to two years following acute COVID-19, patients exhibit signs of unresolved low-grade inflammation and impaired endothelial vasomotor function, which underlie persistent PCS symptoms, including chronic fatigue and diminished quality of life.

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