ArticleiScience2023
Inhalation of ACE2 as a therapeutic target on sex-bias differences in SARS-CoV-2 infection and variant of concern.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- The CCR2 inflammatory pathway is a target for improving severe disease and pulmonary inflammation in experimental COVID-19.Virulence · 2026Article
- A decoy virus strategy using plant-produced SARS-CoV-2 virus-like-particles to inhibit infection and lung injury.Journal of translational medicine · 2026Article
- Inhaled Virus-Mimicking Particles Elicit Dose-Dependent Immune Response against SARS-CoV-2 with Sex-Bias ACE2 Activity in Mice.Nano letters · 2026Article
- Androgens are a Key Factor Affecting Immune Related Diseases.The world journal of men's health · 2026Review
- Persistent neurological and behavioral alterations after SARS-CoV-2 infection in an optimized K18-hACE2 mouse model.Frontiers in microbiology · 2026Article
- Clinical Characteristics and Glucocorticoids Efficacy in COVID-19 Patients with Type 2 Diabetes: A Multicenter Retrospective Study.Infection and drug resistance · 2026Article
- Understanding sex and gender disparities in COVID-19 mortality: a narrative review beyond biology.Biology of sex differences · 2025Review
- Sex differences in tissue-specific immunity and immunology.Science (New York, N.Y.) · 2025Review
- Delayed viral clearance and altered inflammatory responses affect severity of SARS-CoV-2 infection in aged mice.Immunity & ageing : I & A · 2025Article
- Pathogenesis and transmission of SARS-CoV-2 D614G, Alpha, Gamma, Delta, and Omicron variants in golden hamsters.Npj viruses · 2025Article
- A comparative analysis of estrogen receptors, ACE2 and cytokines in pre-and postmenopausal women and men with COVID-19.Frontiers in public health · 2025Article
- Endothelial Cell-Derived Extracellular Vesicles Promote Aberrant Neutrophil Trafficking and Subsequent Remote Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
Corrections and comments
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Authors and funding
25 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.