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Sex differences in viral entry protein expression and host transcript responses to SARS-CoV-2
Mengying Sun1, Rama Shankar2, Meehyun Ko3
1Department of Computer Science and Engineering, Michigan State University, East Lansing, Michigan, USA.
Research Square
|November 11, 2020
Summary
Men show higher expression of viral entry genes ACE2 and TMPRSS2, particularly in the kidney. This biological difference may explain higher COVID-19 mortality rates in males.
Area of Science:
- Genomics
- Immunology
- Nephrology
Background:
- Epidemiological data indicates higher COVID-19 mortality in males.
- The biological basis for this sex disparity remains largely unknown.
Purpose of the Study:
- To investigate sex differences in gene expression of viral entry proteins (ACE2, TMPRSS2) and host responses to SARS-CoV-2.
- To explore potential biological mechanisms underlying COVID-19 sex disparity.
Main Methods:
- Large-scale analysis of 220,000 human gene expression profiles.
- Meta-analysis of clinical data from 6,031 COVID-19 patients.
- Computational deconvolution of gene expression profiles from upper airway and blood samples.
Main Results:
- Male samples exhibit higher ACE2 and TMPRSS2 expression than female samples, especially in older individuals and kidney tissue.
- Male COVID-19 patients show elevated creatinine levels, indicating impaired kidney function.
- Distinct transcriptional responses to SARS-CoV-2 observed between sexes, with enriched kidney-specific mesangial cells in blood of male patients.
Conclusions:
- Biological sex differences in the kidney may contribute to the observed disparity in COVID-19 outcomes.
- Higher expression of viral entry genes in males, particularly in the kidney, could facilitate infection and disease severity.
- Distinct host responses suggest sex-specific pathways are involved in COVID-19 pathogenesis.
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