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Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

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Published on: December 23, 2020

Human ACE2 Polymorphisms from Different Human Populations Modulate SARS-CoV-2 Infection.

Pan Hu¹, Vanessa L Bauer², Sara L Sawyer²

¹Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

|July 27, 2022

Summary

Genetic variations in the human ACE2 gene influence SARS-CoV-2 infection and COVID-19 severity. Specific ACE2 polymorphisms may increase or decrease infection risk, potentially explaining ethnic differences in disease outcomes.

Keywords:

COVID-19 SARS-CoV-2 human ACE2 infection polymorphisms

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Published on: June 14, 2022

Area of Science:

Genetics
Virology
Epidemiology

Background:

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant global mortality.
Variability in COVID-19 symptoms suggests a role for genetic and environmental factors.
The ACE2 gene encodes the primary receptor for SARS-CoV-2 entry into human cells.

Purpose of the Study:

To investigate the impact of human ACE2 (hACE2) gene polymorphisms on SARS-CoV-2 infection susceptibility and COVID-19 symptom severity.
To determine if naturally occurring hACE2 variants affect viral entry and disease progression.

Main Methods:

Analysis of naturally occurring hACE2 polymorphisms in the human population.
Comparison of SARS-CoV-2 infection rates and severity associated with different hACE2 variants versus wild-type.
Assessment of hACE2 variant effects on viral entry without altering cell surface expression levels.

Main Results:

Several hACE2 variants (S19P, I21V, E23K, K26R, K31R, N33I, H34R, E35K, T92I) demonstrated increased SARS-CoV-2 infection.
Specific variants (K26R, T92I) showed a three-fold increase in infection without affecting ACE2 surface levels.
Other variants (D38V, Y83H, I468V, N638S) exhibited reduced infection, suggesting a protective effect.
D38V and Y83H variants decreased SARS-CoV-2 infection by four- and ten-fold, respectively, without altering surface expression.
Protective hACE2 polymorphisms were predominantly found in Asian populations.

Conclusions:

hACE2 gene polymorphisms significantly modulate host susceptibility to SARS-CoV-2 infection.
Certain hACE2 variants may increase the risk of severe COVID-19, while others offer protection.
The prevalence of protective hACE2 variants in specific ethnic groups may partially explain observed differences in COVID-19 mortality rates worldwide.