Circulating angiogenic progenitor cell apoptosis in Post-COVID-19 syndrome

Background: Cellular endothelial dysfunction in patients recovering from Coronavirus disease 2019 (COVID-19) remains poorly understood. This study examined circulating angiogenic progenitor cells (CAC) and mature endothelial cells (CEC) in individuals with persistent symptoms following hospitalization for COVID-19 (PH-PCS) at ≥ 18-months post-infection. Methods: We compared PH-PCS (n = 14) to matched controls without symptomatic COVID-19 (n = 7). Examinations included macro- and microvascular structure and function and the analysis of CAC and CEC using flow cytometry. Results: Estimates indicated somewhat lower apoptotic CAC concentrations (mean differencemd 95 %CI = 0.050 cells/µl 0.003, 0.137, p = 0.084) and proportions (% total CAC, 7.7 percentage points (pp) 0.3, 12.9, p = 0.066) in patients compared to controls, though estimates were imprecise. Similar results were observed for apoptotic CEC concentrations (1.202 cells/µl 0.040, 7.518, p = 0.066) and proportions (% total CEC, 2.7 pp 0.2, 23.8, p = 0.048). Live CAC (-7.6 pp -12.7, -1.1, p = 0.084) and live CEC proportions (-4.9 pp -23.7, -0.3, p = 0.042) were somewhat enhanced in PH-PCS. Brachial-arterial flow-mediated dilation (baFMD) and retinal vessel imaging parameters showed little evidence for differences between groups, except for maximal arteriolar constriction, where estimates suggested on average higher values in PH-PCS (md 95 %CI = 1.64 0.050, 3.63, p = 0.084), but estimates were uncertain. Pooling PH-PCS and controls, correlations were observed between reduced baFMD and both elevated total CEC concentrations (ρ = -0.56, p = 0.038) and decreased apoptotic CAC proportions (ρ = 0.56, p = 0.042). Conclusions: This study suggests the possibility of unbalanced CAC and CEC apoptosis in PH-PCS, but with uncertain magnitude. The findings might inform hypothesis generation for future studies on (cellular) endothelial function in PH-PCS.