Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19); a worldwide pandemic as declared by the World Health Organization (WHO). SARS-CoV-2 appears to infect cells by first binding and priming its viral-spike proteins with membrane-associated angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Through the coordinated actions of ACE2 and TMPRSS2, SARS-CoV-2 spike proteins fuse with plasma membranes and ultimately the virus enters cells. ACE2 is integral to the renin-angiotensin-aldosterone system (RAAS), and SARS-CoV-2 down-regulates protein expression levels of ACE2. Once infected, patients typically develop acute respiratory distress syndrome (ARDS) and a number of other severe complications that result in a high rate of fatality, especially in older (>60 years) adults and in people with pre-existing medical conditions. Data now indicate clearly that among people of all age groups, COVID-19 fatalities are higher in men than women. Here, attention is focused on these sex differences and posit a role of estrogen in these differences as well as possible therapeutic and protective actions of 17β-estradiol against COVID-19.
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