New laboratory evidence for the association between endothelial dysfunction and COVID-19 disease progression.

Abstract

There is growing evidence that angiotensin‐converting enzyme 2 is highly expressed on endothelial cells, endothelial dysfunction plays a critical role in coronavirus disease 2019 (COVID‐19) progression, but laboratory evidence is still lacking. This study established a multicenter retrospective cohort of 966 COVID‐19 patients from three hospitals in Wuhan, China. We found that male (62.8% vs. 46.5%), old age [72 (17) vs. 60.5 (21)], and coexisting chronic diseases (88.5% vs. 60.0%) were associated with poor clinical prognosis in COVID‐19. Furthermore, the deteriorated patients exhibited more severe multiorgan damage, coagulation dysfunction, and extensive inflammation. Additionally, a cross‐sectional study including 41 non‐COVID‐19 controls and 39 COVID‐19 patients assayed endothelial function parameters in plasma and showed that COVID‐19 patients exhibited elevated vascular cell adhesion molecule‐1 (VCAM‐1) (median [IQR]: 0.32 [0.27] vs. 0.17 [0.11] μg/ml, p < 0.001), E‐selectin (21.06 [12.60] vs. 11.01 [4.63] ng/ml, p < 0.001), tissue‐type plasminogen activator (tPA) (0.22 [0.12] vs. 0.09 [0.04] ng/ml, p < 0.001), and decreased plasminogen activator inhibitor‐1 (0.75 [1.31] vs 6.20 [5.34] ng/ml, p < 0.001), as compared to normal controls. Moreover, VCAM‐1 was positively correlated with d‐dimer (R = 0.544, p < 0.001); tPA was positively correlated with d‐dimer (R = 0.800, p < 0.001) and blood urea nitrogen (R = 0.638, p < 0.001). Our findings further confirm the strong association between endothelial dysfunction and poor prognosis of COVID‐19, which offers a rationale for targeting endothelial dysfunction as a therapeutic strategy for COVID‐19.