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

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.

Extracellular vesicles: new players in regulating vascular barrier function.

Extracellular vesicles (EVs) have attracted rising interests in the cardiovascular field not only because they serve as serological markers for circulatory disorders but also because they participate in important physiological responses to stress and inflammation. In the circulation, these membranous vesicles are mainly derived from blood or vascular cells, and they carry cargos with distinct molecular signatures reflecting the origin and activation state of parent cells that produce them, thus providing a powerful tool for diagnosis and prognosis of pathological conditions. Functionally, circulating EVs mediate tissue-tissue communication by transporting bioactive cargos to local and distant sites, where they directly interact with target cells to alter their function. Recent evidence points to the critical contributions of EVs to the pathogenesis of vascular endothelial barrier dysfunction during inflammatory response to injury or infection. In this review, we provide a brief summary of the current knowledge on EV biology and advanced techniques in EV isolation and characterization. This is followed by a discussion focusing on the role and mechanisms of EVs in regulating blood-endothelium interactions and vascular permeability during inflammation. We conclude with a translational perspective on the diagnostic and therapeutic potential of EVs in vascular injury or infectious diseases, such as COVID-19.

The application of Temporary Ark Hospitals in controlling COVID-19 spread: The experiences of one Temporary Ark Hospital, Wuhan, China.

Coronavirus disease 2019 (COVID-19) had its evolution in Wuhan, Hubei Province, China, and now it has spread around the world, resulting in a large number of deaths. Temporary Ark hospitals (TAHs) have played an important role in controlling the spread of the epidemic in the city of Wuhan. Taking one TAH with 800 beds as an example, we summarized details of the layout, setting, working mode of medical staff, patient management, admission standards, discharge standards, and standards for transferring to another hospital, hospital operation, and so on. Over the period of operation, a total of 1124 patients were admitted for treatment. Of these, 833 patients were cured and discharged from the hospital and 291 patients were transferred to other designated hospitals, owing to aggravation of their condition. The achievement was to have zero infection for medical staff, zero in-hospital deaths among admitted patients, and zero readmission for discharged patients. The rapid deployment of TAH provided a suitable place for treating mild/moderate or no asymptomatic COVID-19 patients, which successfully helped to control the infection in Wuhan. The successful model of TAH would rapidly and effectively control the spread of COVID-19 in other cities.