{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:24:46Z","timestamp":1785435886450,"version":"3.56.0"},"reference-count":23,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>COVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. We propose that blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS). In addition, this pathway might indirectly be responsive to anti-inflammatory agents.<\/jats:p>","DOI":"10.7554\/elife.57555","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T08:00:34Z","timestamp":1587974434000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.57555","source":"Crossref","is-referenced-by-count":243,"title":["Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1121-4894","authenticated-orcid":true,"given":"Frank L","family":"van de Veerdonk","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands"},{"name":"Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"van Deuren","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos WM","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quirijn","family":"de Mast","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"van der Hoeven","sequence":"additional","affiliation":[{"name":"Intensive Care, Radboudumc Center for Infectious Diseases (RCI), Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1042\/CS20200163","article-title":"Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?","volume":"134","author":"Batlle","year":"2020","journal-title":"Clinical Science"},{"key":"bib2","first-page":"1","article-title":"Bioregulation of kinins: kallikreins, Kininogens, and kininases","volume":"44","author":"Bhoola","year":"1992","journal-title":"Pharmacological Reviews"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111117","article-title":"An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies","volume":"9","author":"Ceravolo","year":"2014","journal-title":"PLOS ONE"},{"key":"bib4","volume-title":"Assessment Report:\u00a0Firazyr, INN-Icatibant","author":"European Medicines Agency","year":"2014","unstructured":"European Medicines Agency. 2014. 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