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Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies

Clinical and epidemiological studies have identified male sex as an important risk factor for COVID-19 clinical outcomes and mortality. This raises the question as to how this risk factor can be addressed in the prognosis, clinical management, and the treatment of patients with Coronavirus disease 2...

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Autores principales: Galbadage, Thushara, Peterson, Brent M., Wang, Jeffrey S., Jayasekara, Avishka, Ramirez, Danny A., Awada, Joseph, Walsh, John P., Gunasekera, Richard S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753152/
https://www.ncbi.nlm.nih.gov/pubmed/33364247
http://dx.doi.org/10.3389/fmed.2020.589060
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author Galbadage, Thushara
Peterson, Brent M.
Wang, Jeffrey S.
Jayasekara, Avishka
Ramirez, Danny A.
Awada, Joseph
Walsh, John P.
Gunasekera, Richard S.
author_facet Galbadage, Thushara
Peterson, Brent M.
Wang, Jeffrey S.
Jayasekara, Avishka
Ramirez, Danny A.
Awada, Joseph
Walsh, John P.
Gunasekera, Richard S.
author_sort Galbadage, Thushara
collection PubMed
description Clinical and epidemiological studies have identified male sex as an important risk factor for COVID-19 clinical outcomes and mortality. This raises the question as to how this risk factor can be addressed in the prognosis, clinical management, and the treatment of patients with Coronavirus disease 2019 (COVID-19). Currently, there are no guidelines or protocols to help alter the course of sex-specific COVID-19 prognosis, especially in severe disease presentations. This is partly due to the lack of research studies characterizing the differences in male vs. female host response to the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and a lack of a well-rounded understanding of the molecular mechanisms involved. Here, we discuss three distinct but interconnected molecular-level differences in males and females that likely play an essential role in the COVID-19 prognosis. We review interactions of SARS-CoV-2 with host cell angiotensin-converting enzyme 2 (ACE2) in the viral entry between males vs. females and discuss the differential regulation of the renin-angiotensin system (RAS) between the two sexes. Next, we present immune response disparities and how immune function and endocrine regulation may render males increasingly vulnerable to severe COVID-19. We describe the interconnected roles of these three regulatory systems in males and females in response to SARS-CoV-2 infection. Finally, we highlight the clinical implications of these mechanisms to patients with COVID-19 and propose putative targeted therapies that can help reduce COVID-19 severity in those critically ill.
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spelling pubmed-77531522020-12-23 Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies Galbadage, Thushara Peterson, Brent M. Wang, Jeffrey S. Jayasekara, Avishka Ramirez, Danny A. Awada, Joseph Walsh, John P. Gunasekera, Richard S. Front Med (Lausanne) Medicine Clinical and epidemiological studies have identified male sex as an important risk factor for COVID-19 clinical outcomes and mortality. This raises the question as to how this risk factor can be addressed in the prognosis, clinical management, and the treatment of patients with Coronavirus disease 2019 (COVID-19). Currently, there are no guidelines or protocols to help alter the course of sex-specific COVID-19 prognosis, especially in severe disease presentations. This is partly due to the lack of research studies characterizing the differences in male vs. female host response to the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and a lack of a well-rounded understanding of the molecular mechanisms involved. Here, we discuss three distinct but interconnected molecular-level differences in males and females that likely play an essential role in the COVID-19 prognosis. We review interactions of SARS-CoV-2 with host cell angiotensin-converting enzyme 2 (ACE2) in the viral entry between males vs. females and discuss the differential regulation of the renin-angiotensin system (RAS) between the two sexes. Next, we present immune response disparities and how immune function and endocrine regulation may render males increasingly vulnerable to severe COVID-19. We describe the interconnected roles of these three regulatory systems in males and females in response to SARS-CoV-2 infection. Finally, we highlight the clinical implications of these mechanisms to patients with COVID-19 and propose putative targeted therapies that can help reduce COVID-19 severity in those critically ill. Frontiers Media S.A. 2020-12-08 /pmc/articles/PMC7753152/ /pubmed/33364247 http://dx.doi.org/10.3389/fmed.2020.589060 Text en Copyright © 2020 Galbadage, Peterson, Wang, Jayasekara, Ramirez, Awada, Walsh and Gunasekera. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Galbadage, Thushara
Peterson, Brent M.
Wang, Jeffrey S.
Jayasekara, Avishka
Ramirez, Danny A.
Awada, Joseph
Walsh, John P.
Gunasekera, Richard S.
Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies
title Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies
title_full Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies
title_fullStr Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies
title_full_unstemmed Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies
title_short Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies
title_sort molecular mechanisms lead to sex-specific covid-19 prognosis and targeted therapies
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753152/
https://www.ncbi.nlm.nih.gov/pubmed/33364247
http://dx.doi.org/10.3389/fmed.2020.589060
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