Let’s talk about sex in the context of COVID-19

Abstract

In recent months, the coronavirus disease 2019 (COVID-19) pandemic has sent many countries into crisis. Studies have shown that this virus causes worse outcomes and a higher mortality in men than in women. It has been recognized that sex can affect the immune response to a pathogenic agent, as well as the susceptibility for some respiratory diseases. These different responses in males and females may be related to the actions of sex hormones. Angiotensin-converting enzyme 2 (ACE2) acts as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. The expression of ACE2 is influenced by sex hormones; therefore, we discuss in this article that this could be one of the reasons why COVID-19 is more prevalent in men than in women.

Evidence of gender bias in the diagnosis and management of COVID-19 patients: A Big Data analysis of Electronic Health Records

“…7,8,9 Some hypotheses underscore the influence of hormonal factors, 10 immune response, 11 differential distribution of the ACE-2 receptors, and smoking habits, 12 among others. 13 To further characterize the gendered impact of COVID-19, here we aimed to address whether the frequency and severity of COVID-19 affect women differently than men. In addition, we sought to explore the factors underlying these differences.…”

Sex differences in COVID-19 course and outcome: progesterone should not be neglected

“…to the editor : Almost immediately after the pandemic outbreak in China, sex differences in COVID-19 vulnerability and clinical presentation were observed ( 9 , 17 , 23 ), indicating some protective mechanism in females. A reasonable biological explanation was offered by well-known estrogen ability to boost immune response and likely modulate angiotensin-converting enzyme 2 (ACE2) expression ( 4 , 6 , 18 , 22 ), which should imply a lower rate of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in females because of the more robust immune response. However, recent retrospective studies using large, pooled sex-disaggregated data from countries worldwide find no differences in the number of COVID-19 cases between the sexes, but higher severity [according to the number of hospitalizations and intensive care unit (ICU) admissions] and case fatality in males ( 7 , 16 ).…”

“…In that terms, lower COVID-19 vulnerability in females could be provided by progesterone, rather than estrogen. Namely, progesterone is well known for its immunosuppressive and anti-inflammatory effects ( 6 , 13 , 15 , 18 ) that could mitigate hyperinflammatory reaction counteracting cytokine storm development. Progesterone has been shown to stimulate T regulatory cell (Treg) differentiation, restrain Th17 responses but enhance interferon-alpha (IFN-α) pathways ( 10 , 13 , 18 ), which all together could be of particular importance for keeping the viral replication under control, but without excessive and self-reinforcing inflammation.…”

Identifying Pathways and Networks Associated With the SARS-CoV-2 Cell Receptor ACE2 Based on Gene Expression Profiles in Normal and SARS-CoV-2-Infected Human Tissues

“…Females have a lower disease severity and mortality risk than males infected with SARS-CoV-2 (Jin et al, 2020;Wenham et al, 2020). A potential explanation is a different host immune response to SARS-CoV-2 infection between females and males (Moulton, 2018;Chen et al, 2020;Gargaglioni and Marques, 2020;Li et al, 2020). We analyzed the correlations between the expression levels of estrogen and androgen receptor genes (ESR1, ESR2, and AR) and ACE2 expression levels in pan-tissue.…”