Altered Vascular Endothelium-Dependent Responsiveness in Frail Elderly Patients Recovering from COVID-19 Pneumonia: Preliminary Evidence

Abstract

We evaluated vascular dysfunction with the single passive leg movement test (sPLM) in 22 frail elderly patients at 84 + 31 days after hospitalization for COVID-19 pneumonia, compared to 22 age-, sex- and comorbidity-matched controls (CTRL). At rest, all COVID-19 patients were in stable clinical condition without severe comorbidities. Patients (aged 72 ± 6 years, 73% male) had moderate disability (Barthel index score 77 ± 26), hypoxemia and normocapnia at arterial blood gas analysis and mild pulmonary restriction at spirometry. Values of circulating markers of inflammation (C-reactive protein: CRP; erythrocyte sedimentation rate: ESR) and coagulation (D-dimer) were: 27.13 ± 37.52 mg/dL, 64.24 ± 32.37 mm/1 h and 1043 ± 729 ng/mL, respectively. At rest, femoral artery diameter was similar in COVID-19 and CTRL (p = 0.16). On the contrary, COVID-19 infection deeply impacted blood velocity (p = 0.001) and femoral blood flow (p < 0.0001). After sPLM, peak femoral blood flow was dramatically reduced in COVID-19 compared to CTRL (p = 0.001), as was blood flow ∆peak (p = 0.05) and the area under the curve (p < 0.0001). This altered vascular responsiveness could be one of the unknown components of long COVID-19 syndrome leading to fatigue, changes in muscle metabolism and fibers’ composition, exercise intolerance and increased cardiovascular risk. Impact of specific treatments, such as exercise training, dietary supplements or drugs, should be evaluated.

An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Altered endothelial dysfunction-related microRNAs were found in plasma from ME/CFS patients recently [ 5 ]. In Covid-19 infection the endothelium is severely affected and the disturbance seems to persist in post-Covid Syndrome (PCS) [ 8 , 12 , 20 , 23 , 34 ]. Particularly the finding of severe endothelial affection in Covid-19 and the persisting endothelial dysfunction corroborates our hypothesis of a role of endothelial and vascular dysfunction in the pathogenesis of PCS.…”

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

“…40, 42, 43 Chronotropic incompetence is also associated with impaired endothelial function assessed by brachial flow-mediated vasodilation 44 and abnormal endothelial function has been demonstrated to be present in the setting of early PASC. 45, 46 Abnormal endothelial function assessed with non-invasive brachial artery flow-mediated dilation may be associated with reduced VO 2 in PASC. 47 Coronary microvascular dysfunction, present in some people recovering from COVID-19, 48 is also associated with chronotropic incompetence in the general population with microvascular dysfunction.…”

“…48 Endothelial and coronary microvascular dysfunction are associated with chronotropic incompetence in the general population 49–51 and have been demonstrated in early PASC. 52–54 Endothelial dysfunction may be associated with reduced VO 2 in PASC; 55 this could be due to endothelial injury from direct viral infection, or due to effects of persistent inflammation and immune activation. 56 Elevated inflammation resulting in changes in autonomic function in PASC could explain reduced exercise capacity, chronotropic incompetence, blunted heart rate recovery, reduced heart rate variability and CPET findings others have noted in PASC including altered peripheral oxygen extraction, 57 preload failure 58 or inadequate stroke volume augmentation, 23, 24 and disordered breathing.…”

l-Arginine and COVID-19: An Update

“…We speculate that L-Arginine supplementation could be also beneficial in controlling long-COVID-19, since the persistence of chronic inflammation and endothelial dysfunction has been shown to be fundamental in COVID-19 sequelae [90][91][92][93].…”