{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:14:49Z","timestamp":1789578889412,"version":"build-2803163510"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH127856"],"award-info":[{"award-number":["R01MH127856"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20CDA35310306"],"award-info":[{"award-number":["20CDA35310306"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NATIONAL INSTITUTE OF AGING","award":["R21AG070860"],"award-info":[{"award-number":["R21AG070860"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Male sex has been identified as a risk factor for worse COVID-19 outcomes. This sex difference has been mostly attributed to the complex role of sex hormones. Cell surface entry of SARS-CoV-2 is mediated by the transmembrane protease serine 2 (TMPRSS2) which is under transcriptional regulation by androgens. P450 aromatase enzyme converts androgens to estrogens. This study measured concentrations of aromatase enzyme, testosterone, estradiol, and TMPRSS-2 in plasma of hospitalized COVID-19 patients to elucidate the dynamics of sex-linked disparity in COVID-19 and correlate them with disease severity and mortality.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this prospective cohort study, a total of 265 patients (41% women), age 18 years and older, who had a positive COVID-19 PCR test and were hospitalized for COVID-19 at Memorial Hermann Hospital in Houston, (between May 2020 and May 2021) were enrolled in the study if met inclusion criteria. Plasma concentrations of Testosterone, aromatase, TMPRSS-2, and estradiol were measured by ELISA. COVID-19 patients were dichotomized based on disease severity into moderate-severe (<jats:italic>n<\/jats:italic>\u2009=\u2009146) or critical (<jats:italic>n<\/jats:italic>\u2009=\u2009119). Mann Whitney U and logistic regression were used to correlate the analytes with disease severity and mortality.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>TMPRSS2 (2.5\u2009\u00b1\u20090.31 vs. 1.73\u2009\u00b1\u20090.21 ng\/mL, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and testosterone (1.2\u2009\u00b1\u20090.1 vs. 0.44\u2009\u00b1\u20090.12 ng\/mL, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) were significantly higher in men as compared to women with COVID-19 after adjusting for age in a multivariate model. There was no sex difference seen in the level of estradiol and aromatase in COVID-19 patients. TMPRSS2 and aromatase were higher, while testosterone was lower in patients with increased COVID-19 severity. They were independently associated with COVID-19 severity, after adjusting for several baseline risk factors in a multivariate logistic regression model. In terms of mortality, TMPRRS2 and aromatase levels were significantly higher in non-survivors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our study demonstrates that testosterone, aromatase, and TMPRSS2 are markers of COVID-19 severity. Estradiol levels do not change with disease severity in COVID-19. In terms of mortality prediction, higher aromatase and TMPRSS-2 levels can be used to predict mortality from COVID-19 in hospitalized patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Plain English Summary<\/jats:title>\n                <jats:p>COVID-19 has caused over a million deaths in the U.S., with men often getting sicker than women. Testosterone, a male hormone, helps control a protein called TMPRSS-2, which allows the COVID-19 virus to spread more easily in the body. A protein called aromatase converts the male hormone testosterone into the female hormone estrogen. It is thought that female hormone estrogen helps protect women from getting seriously ill from COVID-19. To understand the role of these hormones in COVID-19 and sex differences, we measured levels of testosterone, estrogen, aromatase (which turns testosterone into estrogen), and TMPRSS-2 in hospitalized COVID-19 patients. We also checked how this level might reflect the severity of the disease. We found that critically ill COVID-19 patients (the ones in ICU) had higher levels of TMPRSS-2 and aromatase, and lower testosterone levels. When we used these hormone levels to predict death in hospitalized COVID-19 patients, higher levels of TMPRSS-2 and aromatase were linked to a lower chance of survival.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13293-024-00658-4","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T09:02:34Z","timestamp":1729760554000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Aromatase, testosterone, TMPRSS2: determinants of COVID-19 severity"],"prefix":"10.1186","volume":"15","author":[{"given":"Eric C.","family":"Mohan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude P. 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