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

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)

 

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

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

 

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