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

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) (odds ratio: 1.000; 95% confidence interval [CI]: 1.000-1.000; p = 0.002), E-selectin (odds ratio: 1.000; 95% CI: 1.000-1.001; p < 0.001), tissue-type plasminogen activator (tPA) (odds ratio: 1.024; 95% CI: 1.014-1.035; p < 0.001), and decreased plasminogen activator inhibitor-1 (odds ratio: 0.995; 95% CI: 0.990-1.000; p = 0.059). 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.