SARS‐Cov‐2 Spike Protein Causes Human Lung Endothelial Inflammation

Abstract

Patients with COVID‐19 often present with pulmonary inflammation and blood coagulopathy, with severe cases advancing to acute respiratory distress syndrome (ARDS) and multiple organ failure. Although the pathogenesis is not completely understood, endothelial inflammation is suspected to be a major causative factor for the systemic manifestations of COVID‐19. In this study, we investigated the direct effects of SARS‐Cov‐2 spike protein on pulmonary microvascular endothelial cells (ECs) isolated from the small airway region of viable human lungs. We verified the expression of angiotensin‐converting enzyme 2 (Ace‐2), the receptor for SARS‐Cov‐2 spike protein, in pulmonary ECs using flow cytometry analysis and immunofluorescence labeling. Treating ECs with recombinant spike protein caused increased F‐actin stress fibers, enhanced phosphorylation of myosin light chain 2, and disruption of adherens junction continuity. In addition to the junction and cytoskeletal changes, spike protein‐treated ECs showed increased expression of intercellular adhesion molecule 1 and enhanced adherence for monocytic cells. Interestingly, there was a significant accumulation of von Willebrand factor long strands on the cell surface in ECs isolated from COVID‐19 positive human lungs, as well as on ECs from normal human lungs following spike protein treatment. In conclusion, we demonstrate that the SARS‐Cov‐2 spike protein is capable of directly activating human lung ECs and promoting inflammation/coagulopathy.