Inhalation of ACE2 as a therapeutic target on sex-bias differences in SARS-CoV-2 infection and variant of concern, 2023

[Sly Saint]

Highlights

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  K18-hACE2 mice show sex-dependent responses to SARS-CoV-2 infection
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  Male and female mice display distinct proteomic signatures in SARS-CoV-2 infection
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  Inhalation of ACE2 reduces SARS-CoV-2 infection via decoy action and ERα modulation
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  Recombinant ACE2 inhibits Delta variant and cytopathic effects in lung organoids

Summary
Despite similar infection rates, COVID-19 has resulted in more deaths in men than women. To understand the underlying mechanisms behind this sex-biased difference in disease severity, we infected K18-human angiotensin converting enzyme 2 (ACE2) mice of both sexes with SARS-CoV-2. Our study revealed a unique protein expression profile in the lung microenvironment of female mice. As a result, they were less vulnerable to severe infection, with higher ACE2 expression and a higher estrogen receptor α (ERα)/androgen receptor (AR) ratio that led to increased antiviral factor levels. In male mice, inhaling recombinant ACE2 neutralized the virus and maintained the ERα/AR ratio, thereby protecting the lungs. Our findings suggest that inhaling recombinant ACE2 could serve as a decoy receptor against SARS-CoV-2 and protect male mice by offsetting ERα-associated protective mechanisms. Additionally, our study supports the potential effectiveness of recombinant ACE2 therapy in human lung organoids infected with the Delta variant.
Graphical abstract

Inhalation of ACE2 as a therapeutic target on sex-bias differences in SARS-CoV-2 infection and variant of concern: iScience (cell.com)

 

[Sly Saint]

article
Men at greater risk of severe Covid - and now experts may know why

Men are more likely to be hospitalized with severe Covid - and the reason may be due to differences between the sexes in levels of the protective ACE2 protein that the virus also uses to gain access to cells.

This is the conclusion of a team of researchers from University of Toronto, who conducted studies on mice into the role of the protein in cases of COVID-19.

They report that men only have one copy of the ACE2 gene - meaning that, when infected, too much of the protein is occupied by the virus and its protective role is compromised.

While the study has only been conducted in mice, it is likely the same mechanism is contributing to sex-based differences in Covid outcomes in humans as well.

Furthermore, the team proposes that synthetic ACE2 proteins might be given to people as protection in high Covid-risk situations, and as a therapy in hospitals.

Men at greater risk of severe Covid - and now experts may know why (msn.com)

 

[Amw66]

And the flip side - woman are more at risk of developing long COVID .