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.

Associated-Onset Symptoms and Post-COVID-19 Symptoms in Hospitalized COVID-19 Survivors Infected with Wuhan, Alpha or Delta SARS-CoV-2 Variant

“…A first finding of our study was that the prevalence of post-COVID-19 fatigue (70%) was similar between the three SARS-CoV-2 variants suggesting that COVID-19 is associated with long-lasting post-fatigue, sharing common symptoms with myalgic encephalomyelitis/chronic fatigue syndrome [23]. In fact, similar endothelial dysfunction has been found in patients with post-COVID-19 symptoms and those with myalgic encephalomyelitis/chronic fatigue syndrome [24]. It could be hypothesized that although some differences (e.g., higher viral load, higher transmissibility, potential reinfections) between SARS-CoV-2 variants have been identified, the pathogenic cell-to-cell mechanisms associated with the development of post-COVID-19 fatigue may be similar between all variants.…”

Exercise Intolerance in Post-Acute Sequelae of COVID-19 and the Value of Cardiopulmonary Exercise Testing- a Mini-Review

“…However, such impaired diffusion could also be explained by direct damage to the endothelium (40) leading to exercise intolerance as observed in chronic fatigue syndrome (41). Similarly, endothelial dysfunction has been reported in PASC with and without chronic fatigue syndrome (42). Interestingly, all the aforementioned factors may be linked to autonomic dysregulation (43,44).…”

Sequelae of COVID-19 among previously hospitalized patients up to 1 year after discharge: a systematic review and meta-analysis

“…An investigation of autopsy samples demonstrated viral persistence, resulting in multiple organ injury and various clinical presentations [ 107 ]. The role of inflammatory biomarkers in its pathogenesis is discordant since some studies have observed a persistently elevated biomarkers [ 103 , 108 , 109 ], while some researchers also show there is no direct correlations between them [ 110 ].…”