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ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19

Donato Zipeto¹, Julys da Fonseca Palmeira², Gustavo A Argañaraz²

¹Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Frontiers in Immunology

|October 29, 2020

Summary

COVID-19 severity in elderly, comorbid males may stem from renin-angiotensin system (RAS) imbalance. Overactive ADAM17 and TMPRSS2 proteins contribute to severe inflammation and coagulation in COVID-19 patients.

Area of Science:

Pathophysiology
Virology
Immunology

Background:

Coronavirus Disease 2019 (COVID-19) has caused significant global mortality.
Key comorbidities include cardiovascular disease, hypertension, diabetes, and chronic lung disease.
Severe COVID-19 outcomes are more prevalent in elderly, comorbid males.

Purpose of the Study:

To review the pathophysiological roles of ACE2, ADAM17, and TMPRSS2 in COVID-19.
To explore mechanisms linking comorbidities and severe COVID-19.
To discuss the impact of renin-angiotensin system (RAS) imbalance on disease severity.

Main Methods:

Literature review focusing on host-pathogen interactions.
Analysis of molecular mechanisms involving ACE2, ADAM17, and TMPRSS2.
Discussion of genetic factors influencing protein expression and activity.

Main Results:

Renin-angiotensin system (RAS) imbalance, mediated by ACE2 and ADAM17, is implicated in COVID-19 severity.
Overexpression of ADAM17 leads to increased secretion of ACE2, TNF-α, and IL-6R, promoting inflammation and coagulation.
TMPRSS2 expression is identified as a critical genetic factor influencing COVID-19 clinical outcomes.

Conclusions:

ADAM17 and TMPRSS2 over-activation may drive severe inflammatory responses and coagulation in COVID-19.
Understanding these host protein interactions is crucial for predicting and managing severe COVID-19.
Targeting these pathways could offer therapeutic strategies for high-risk patients.

Keywords:

ACE2 ADAM17 COVID-19 pathophysiology SARS-CoV-2 TMPRSS2

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