{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T21:26:20Z","timestamp":1774128380117,"version":"3.50.1"},"reference-count":39,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Viral Immunology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a marked tropism for the biliary tract; it damages the bile ducts and hepatocytes and can lead to liver decompensation, cirrhosis, and sepsis. The pathogenesis of liver damage and its association with damage to the lung, heart, and brain and to the other protean manifestations of COVID-19 disease are not fully understood. In particular, tissue damage from thinning and leaky blood vessels appears to result from an inflammatory response to the virus rather than the virus itself. This article outlines a new hypothesis of the nature of the inflammatory factor responsible for tissue damage in COVID-19. Review of the literature reveals that COVID-19 disease closely resembles an endogenous form of hypervitaminosis A. We propose that SARS-CoV-2 virus-induced liver damage causes retinoic acid and stored retinyl esters to be released into the circulation in toxic concentrations, unbound to protein, with resulting damage to organs including the lungs, heart, blood vessels, and skin. Several lines of evidence support this model of disease causation. Subject to testing, strategies for the effective treatment and prevention of COVID-19 could include targeting the action and accumulation of retinoids.<\/jats:p>","DOI":"10.1089\/vim.2020.0330","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T15:09:29Z","timestamp":1620918569000},"page":"376-379","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Liver Damage and Exposure to Toxic Concentrations of Endogenous Retinoids in the Pathogenesis of COVID-19 Disease: Hypothesis"],"prefix":"10.1177","volume":"34","author":[{"given":"Anthony R.","family":"Mawson","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, College of Health Sciences, Jackson State University, Jackson, Mississippi, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley M.","family":"Croft","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences, University of Portsmouth, England, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Gonzalez-Fernandez","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Pathology, University of Mississippi Medical Center, Jackson, Mississippi, USA."},{"name":"Department of Research &amp; Development, GV (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, Mississippi, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"1275","article-title":"Antagonistic effect of glucocorticoids on retinoic acid induced growth inhibition and morphological alterations of a human cell line","volume":"46","author":"Bakke O.","year":"1986","unstructured":"Bakke O. Antagonistic effect of glucocorticoids on retinoic acid induced growth inhibition and morphological alterations of a human cell line. Cancer Res, 1986; 46:1275\u20131279.","journal-title":"Cancer Res"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","unstructured":"Bastard P Rosen LB Zhang Q et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science 2000. 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Evaluation of the effects of oral isotretinoin on nasal function, taste, and smell. B-ENT, 2018; 15:185\u2013190.","journal-title":"B-ENT"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2033369"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2020.02.011"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9785231"},{"key":"e_1_3_4_21_2","unstructured":"LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda MD: National Institute of Diabetes and Digestive and Kidney Diseases 2012. Vitamin A. [Updated December 3 2013]. Available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548165 (accessed May7 2021)."},{"key":"e_1_3_4_22_2","first-page":"m1252","article-title":"Clues to understanding the pathogenesis of coronavirus infection (COVID-19 and SARS-CoV)","volume":"368","author":"Mawson AR","year":"2020","unstructured":"Mawson AR, , Croft AM, , Gonzalez-Fernandez F. 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