Abstract
In the face of the Covid-19 pandemic, an intensive number of studies have been performed to understand in a deeper way the mechanisms behind better or worse clinical outcomes. Epidemiologically, men subjects are more prone to severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) infections than women, with a similar scenario being also stated to the previous coronavirus diseases, namely, SARS-CoV in 2003 and Middle East Respiratory Syndrome coronavirus diseases (MERS-CoV) in 2012. In addition, and despite that aging is regarded as an independent risk factor for the severe form of the disease, even so, women protection is evident. In this way, it has been expected that sex hormones are the main determinant factors in gender differences, with the immunomodulatory effects of estrogen in different viral infections, chiefly in Covid-19, attracting more attention as it might explain the case-fatality rate and predisposition of men for Covid-19 severity. Here, we aim to provide a mini-review and an overview on the protective effects of estrogen in Covid-19. Different search strategies were performed including Scopus, Web of Science, Medline, Pubmed, and Google Scholar database to find relative studies. Findings of the present study illustrated that women have a powerful immunomodulating effect against Covid-19 through the effect of estrogen. This study illustrates that estrogens have noteworthy anti-inflammatory and immuno-modulatory effects in Covid-19. Also, estrogen hormone reduces SARS-CoV-2 infectivity through modulation of pro-inflammatory signaling pathways. This study highlighted the potential protective effect of estrogen against Covid-19 and recommended for future clinical trial and prospective studies to elucidate and confirm this protective effect.
Highlights
Coronavirus disease 19 (Covid-19) is a global pandemic danger caused by the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2)
Reduction of angiotensin-converting enzyme 2 (ACE2) leads to vasoconstriction, hypertension, coagulopathy, and induction of inflammatory reactions that together increase the risk of acute lung injury (ALI) and Covid-19 severity [3]
In SARS-CoV, the case-fatality rate was 22% for men compared to 13% for women, while in MERS-CoV the case-fatality rate was 52% for men compared to 23% for women [5]
Summary
Coronavirus disease 19 (Covid-19) is a global pandemic danger caused by the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2). SARS-CoV-2 spike protein binds to angiotensin-converting enzyme 2 (ACE2) receptors [1], which are involved in the viral entry Such receptors are highly expressed in different tissues, mainly in lung pneumocyte type II cells, with SARS-CoV-2 bindings to ACE2 leading to downregulation of protective ACE2 and induction of Estrogen Effects in Covid-19 hyper-inflammation and oxidative stress, with consequent progress of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [2]. Related to the X chromosomes, TLR7 is higher in women than in men and its expression leads to higher immune responses, these reactions can cause autoimmune phenomena [12] Both immunoglobulins and circulating T cells are higher in women compared to men, so that women’s immune reactivity is more active against different viral infections, which predispose them for risk of autoimmunity [13]. Women have an average higher frequency of circulating CD4 T cells than men and clinical studies reveal that men have lower CD3 and CD4 T cell counts, CD4/CD8 T cell ratios, and helper T cell type 1 (Th1)
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