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The lung is the major target organ of COVID\u201019, wherein the primary cause of mortality is hypoxic respiratory failure, resulting from acute respiratory distress syndrome, with severe hypoxemia, often requiring assisted ventilation. While similar in some ways to acute respiratory distress syndrome secondary to other causes, lungs of some patients dying with COVID\u201019 exhibit distinct features of vascular involvement, including severe endothelial injury and cell death via apoptosis and\/or pyroptosis, widespread capillary inflammation, and thrombosis. Furthermore, the pulmonary pathology of COVID\u201019 is characterized by focal inflammatory cell infiltration, impeding alveolar gas exchange resulting in areas of local tissue hypoxia, consistent with potential amplification of COVID\u201019 pathogenicity by hypoxia. Vascular endothelial cells play essential roles in both innate and adaptive immune responses, and are considered to be \u201cconditional innate immune cells\u201d centrally participating in various inflammatory, immune pathologies. Activated endothelial cells produce cytokines\/chemokines, dynamically recruit and activate inflammatory cells and platelets, and centrally participate in pro\u2010thrombotic processes (thrombotic microangiopathies). Initial reports presented pathological findings of localized direct infection of vascular endothelial cells with SARS\u2010CoV\u20102, yet emerging evidence does not support direct infection of endothelial or other vascular wall cell and thus widespread endothelial cell dysfunction and inflammation may be better explained as secondary responses to epithelial cell infection and inflammation. Endothelial cells are also actively engaged in a cross\u2010talk with the complement system, the essential arm of innate immunity. Recent reports present evidence for complement deposition in SARS\u2010CoV\u20102\u2010damaged lung microcirculation, further strengthening the idea that, in severe cases of COVID\u201019, complement activation is an essential player, generating destructive hemorrhagic, capillaritis\u2010like tissue damage, clotting, and hyperinflammation. Thus, complement\u2010targeted therapies are actively in development. This review is intended to explore in detail these ideas.<\/jats:p>","DOI":"10.1177\/20458940211015799","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T10:50:43Z","timestamp":1619175043000},"page":"1-14","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":40,"title":["Mechanisms of SARS\u2010CoV\u20102\u2010induced lung vascular disease: potential role of complement"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6918-6411","authenticated-orcid":false,"given":"Kurt R.","family":"Stenmark","sequence":"first","affiliation":[{"name":"Divisions of Pediatric Critical Care Medicine and Cardiovascular Pulmonary Research University of Colorado Denver Denver CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria G.","family":"Frid","sequence":"additional","affiliation":[{"name":"Divisions of Pediatric Critical Care Medicine and 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