{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:11:06Z","timestamp":1787019066783,"version":"build-2736575974"},"reference-count":74,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"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":["Neuroscientist"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>The prevailing evidence suggests that patients with severe COVID-19 seem to have an overreaction of the immune system demonstrating exacerbated levels of inflammation caused by a \u201ccytokine storm.\u201d At this early stage, the mechanisms underpinning COVID-19 are still subject to intense scrutiny and the long-term mental health consequences as a result of the disease are unknown. Here we discuss the hypothesis that patients who survive severe COVID-19 and who experience significant activation of the immune system, are at greater risk of developing depression. We posit that a phenomenon known as cytokine storm dramatically activates the enzyme indoleamine 2,3-dioxygenase (IDO-1), resulting in the increase in kynurenine metabolites. Kynurenine is metabolized by IDO-1 in the brain, producing chemokines, in which a prolonged exposure may result long-term brain impairment. In this article, we also propose the possibility that a SARS-CoV-2 neuroinvasion increases the local levels of angiotensin II by angiotensin-converting enzyme 2 down-regulation. Thereby, angiotensin II could increase kynurenine metabolites producing pro-oxidative and pro-inflammatory effects, resulting in impairment of cognitive function, enhanced oxidative stress and decreased brain-derived neurotrophic factor. It is our premise that patients who experience such a cytokine storm may be at increased risk of long-term mental illness, such as depression.<\/jats:p>","DOI":"10.1177\/1073858420967892","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T07:33:15Z","timestamp":1604302395000},"page":"11-19","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Why Severe COVID-19 Patients Are at Greater Risk of Developing Depression: A Molecular Perspective"],"prefix":"10.1177","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1563-1513","authenticated-orcid":false,"given":"Ana P.","family":"Bou\u00e7as","sequence":"first","affiliation":[{"name":"Sunshine Coast Mind and Neuroscience Thompson Institute, University of the Sunshine Coast, Sunshine Coast, Queensland, 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