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Risk of severe COVID-19 outcomes is consistently lower in women than men worldwide, suggesting that female biological sex is instrumental in protection. This mini-review discusses the immunomodulatory and anti-inflammatory actions of high physiological concentrations of the steroids 17\u03b2-estradiol (E2) and progesterone (P4). We review how E2 and P4 favor a state of decreased innate immune inflammatory response while enhancing immune tolerance and antibody production. We discuss how the combination of E2 and P4 may improve the immune dysregulation that leads to the COVID-19 cytokine storm. It is intended to stimulate novel consideration of the biological forces that are protective in women compared to men, and to therapeutically harness these factors to mitigate COVID-19 morbidity and mortality.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa127","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T20:56:17Z","timestamp":1596142577000},"source":"Crossref","is-referenced-by-count":232,"title":["Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes"],"prefix":"10.1210","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0874-0754","authenticated-orcid":false,"given":"Franck","family":"Mauvais-Jarvis","sequence":"first","affiliation":[{"name":"Diabetes Discovery & Sex-Based Medicine Laboratory, Section of Endocrinology, John W. 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Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-4177","authenticated-orcid":false,"given":"Ellis R","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biochemistry, University of California, Irvine, California"},{"name":"Long Beach VA Medical Center, Long Beach, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"issue":"3","key":"2021121901012956000_CIT0001","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/aje\/kwh056","article-title":"Do men have a higher case fatality rate of severe acute respiratory syndrome than women do?","volume":"159","author":"Karlberg","year":"2004","journal-title":"Am J Epidemiol."},{"key":"2021121901012956000_CIT0002","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2147\/IJGM.S67061","article-title":"The pattern of middle east respiratory syndrome coronavirus in Saudi Arabia: a descriptive epidemiological analysis of data from the Saudi Ministry of Health","volume":"7","author":"Alghamdi","year":"2014","journal-title":"Int J Gen Med."},{"key":"2021121901012956000_CIT0003","article-title":"Sex and gender: modifiers of health, disease and medicine","author":"Mauvais-Jarvis","journal-title":"Lancet."},{"key":"2021121901012956000_CIT0004","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N Engl J Med."},{"key":"2021121901012956000_CIT0005","article-title":"Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy.","author":"Onder","journal-title":"JAMA"},{"issue":"2","key":"2021121901012956000_CIT0006","doi-asserted-by":"crossref","first-page":"85","DOI":"10.24171\/j.phrp.2020.11.2.05","article-title":"Coronavirus disease-19: the first 7755 cases in the Republic of Korea","volume":"11","author":"COVID-19 National Emergency Response Center, Epidemiology and Case Management Team, Korea Centers for Disease Control and Prevention","year":"2020","journal-title":"Osong Public Health Res Perspect"},{"issue":"20","key":"2021121901012956000_CIT0007","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area","volume":"323","author":"Richardson","year":"2020","journal-title":"JAMA"},{"issue":"6","key":"2021121901012956000_CIT0008","doi-asserted-by":"crossref","first-page":"e1008570","DOI":"10.1371\/journal.ppat.1008570","article-title":"Biological sex impacts COVID-19 outcomes","volume":"16","author":"Klein","year":"2020","journal-title":"PLoS Pathog."},{"issue":"16","key":"2021121901012956000_CIT0009","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1001\/jama.2020.5394","article-title":"Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy","volume":"323","author":"Grasselli","year":"2020","journal-title":"JAMA"},{"key":"2021121901012956000_CIT0010","article-title":"Features of 16 749 hospitalised UK patients with COVID-19 using the ISARIC WHO clinical characterisation protocol. 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