Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and ME/CFS, Haffke, Scheibenbogen et al, 2022

[Kalliope]

Transl Med
Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS) Milan Haffke et al

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.

 

[Kalliope]

Spotted on twitter via prof. Kunst who comments:

In a new #LongCovid study, one in three patients showed endothelial dysfunction (i.e., diminished ability to widen blood vessels when needed). Also of note, 15 of the 30 patients qualified for #MECFS for which this impairment is frequently observed.

 

[ME/CFS Skeptic]

This figure seems to show the main results. Doesn't look like a large difference.

 

[SNT Gatchaman]

The cut-off of 1.67 to define normal / abnormal appears to be derived from comparison of the EndoPAT 2000 device against the gold standard evaluation of endothelial dysfunction: direct catheter left main coronary artery challenge with acetylcholine.

From the manufacturer's Datasheet:

The RHI (Reactive Hyperemia Index) is the post-to-pre occlusion PAT™ signal ratio in the occluded arm, relative to the same ratio in the control arm, corrected for baseline vascular tone of the occluded arm where:

Normal: RHI > 1.67
Abnormal: RHI ≤ 1.67​

This index and threshold were used in the validation study presented at section 1.2 of this manual and they reflect endothelial function.

The gold-standard is defined as:

Normal coronary endothelial function is defined as an increase in CBF of >50% and an increase or less than 20% decrease in the coronary artery diameter in response to the maximum dose of intra-coronary Ach

(ΔCBF > 50% and ΔCAD > -20%)

Fig. 1 in the paper shows that HCs can get close to that threshold.