COVID-19 is associated with endotheliopathy and coagulopathy, potentially leading to multi-organ failure. However, the direct mechanisms by which SARS-CoV-2 infection leads to endothelial damage are unclear. Here we developed an infection-competent human vascular organoid from pluripotent stem cells amenable for modeling endotheliopathy. Longitudinal proteome analysis of COVID-19 patient serume was conducted to gain further insights into molecular mediators that drive vascular complications. Differential signatures were identified by comparing late- and early- recovery groups. In the late recovery group, there were significant increases in FCGBP (anti-inflammation), SFTPB (lung surfactant metabolism), coagulation system (A2M and SERPINA1), and complement proteins (C7, CFHR5, and CFD) on day 1-2.