Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

Abstract

BACKGROUND: Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of  patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue  Syndrome (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis  and damaging the endothelium, we investigated endothelial dysfunction (ED) and  endothelial biomarkers in patients with PCS. METHODS: We studied the endothelial  function in 30 PCS patients with persistent fatigue and exertion intolerance as  well as in 15 age- and sex matched seronegative healthy controls (HCs). 14  patients fulfilled the diagnostic criteria for ME/CFS. The other patients were  considered to have PCS. Peripheral endothelial function was assessed by the  reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) in  patients and HCs. In a larger cohort of patients and HCs, including post-COVID  reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan  (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) and ACE2 were analysed as  endothelial biomarkers. RESULTS: Five of the 14 post-COVID ME/CFS patients and  five of the 16 PCS patients showed ED defined by a diminished RHI (< 1.67), but  none of HCs exhibited this finding. A paradoxical positive correlation of RHI  with age, blood pressure and BMI was found in PCS but not ME/CFS patients. The  ET-1 concentration was significantly elevated in both ME/CFS and PCS patients  compared to HCs and PCHCs. The serum Ang-2 concentration was lower in both PCS  patients and PCHCs compared to HCs. CONCLUSION: A subset of PCS patients display  evidence for ED shown by a diminished RHI and altered endothelial biomarkers.  Different associations of the RHI with clinical parameters as well as varying  biomarker profiles may suggest distinct pathomechanisms among patient subgroups.