{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:46:28Z","timestamp":1792791988357,"version":"4.5.0"},"reference-count":74,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:00:00Z","timestamp":1606608000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This paper attempts to explain how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes the complications that make coronavirus disease 2019 (COVID-19) a serious disease in specific patient subgroups. It suggests that cortisol-associated activation of the mineralocorticoid receptor (MR) in epithelial and endothelial cells infected with the virus stimulates the release of adenosine 5\u2032-triphosphate (ATP), which then acts back on purinergic receptors. In the lung this could produce the nonproductive cough via purinergic P2X3 receptors on vagal afferent nerves. In endothelial cells it could stimulate exocytosis of Weibel-Palade bodies (WPBs) that contain angiopoietin-2, which is important in the pathogenesis of acute respiratory distress syndrome (ARDS) by increasing capillary permeability and von Willebrand factor (VWF), which mediates platelet adhesion to the endothelium and hence clotting. Angiopoietin-2 and VWF levels both are markedly elevated in COVID-19\u2013associated ARDS. This paper offers an explanation for the sex differences in SARS-CoV-2 complications and also for why these are strongly associated with age, race, diabetes, and body mass index. It also explains why individuals with blood group A have a higher risk of severe infection than those with blood group O. Dexamethasone has been shown to be of benefit in coronavirus ARDS patients and has been thought to act as an anti-inflammatory drug. This paper suggests that a major part of its effect may be due to suppression of cortisol secretion. There is an urgent need to trial the combination of dexamethasone and an MR antagonist such as spironolactone to more effectively block the MR and hence the exocytosis of WPBs.<\/jats:p>","DOI":"10.1210\/clinem\/dgaa874","type":"journal-article","created":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T20:56:45Z","timestamp":1606597005000},"page":"622-635","source":"Crossref","is-referenced-by-count":23,"title":["New Horizons: Does Mineralocorticoid Receptor Activation by Cortisol Cause ATP Release and COVID-19 Complications?"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1025-2095","authenticated-orcid":false,"given":"Christopher","family":"Edwards","sequence":"first","affiliation":[{"name":"Department of Medicine, Imperial College School of Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,11,28]]},"reference":[{"issue":"42","key":"2021122117330838600_CIT0001","doi-asserted-by":"crossref","first-page":"15000","DOI":"10.1073\/pnas.0507008102","article-title":"Aldosterone acts via an ATP autocrine\/paracrine system: the Edelman ATP hypothesis revisited","volume":"102","author":"Gorelik","year":"2005","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"2","key":"2021122117330838600_CIT0002","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JOE-12-0341","article-title":"Angiotensin-converting enzyme 2, angiotensin-(1\u20137) and Mas: new players of the renin-angiotensin system","volume":"216","author":"Santos","year":"2013","journal-title":"J Endocrinol."},{"issue":"2","key":"2021122117330838600_CIT0003","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1161\/HYPERTENSIONAHA.107.102764","article-title":"Endothelial dysfunction and elevated blood pressure in Mas gene-deleted mice","volume":"51","author":"Xu","year":"2008","journal-title":"Hypertension."},{"issue":"7047","key":"2021122117330838600_CIT0004","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature03712","article-title":"Angiotensin-converting enzyme 2 protects from severe acute lung failure","volume":"436","author":"Imai","year":"2005","journal-title":"Nature."},{"issue":"4812","key":"2021122117330838600_CIT0005","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1126\/science.3037703","article-title":"Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor","volume":"237","author":"Arriza","year":"1987","journal-title":"Science."},{"issue":"8618","key":"2021122117330838600_CIT0006","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S0140-6736(88)90742-8","article-title":"Localisation of 11\u03b2-hydroxysteroid dehydrogenase\u2014tissue specific protector of the mineralocorticoid receptor","volume":"2","author":"Edwards","year":"1988","journal-title":"Lancet."},{"issue":"1","key":"2021122117330838600_CIT0007","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1172\/JCI113592","article-title":"Syndrome of apparent mineralocorticoid excess. 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