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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.
  • Galbadage T; Department of Kinesiology and Health Science, Biola University, La Mirada, CA, United States.
  • Peterson BM; Department of Kinesiology and Health Science, Biola University, La Mirada, CA, United States.
  • Wang JS; Department of Infectious Diseases, Southern California Permanente Medical Group, Pasadena, CA, United States.
  • Jayasekara A; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, United States.
  • Ramirez DA; Department of Chemistry, Physics, and Engineering, Biola University, La Mirada, CA, United States.
  • Awada J; Department of Chemistry, Physics, and Engineering, Biola University, La Mirada, CA, United States.
  • Walsh JP; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, United States.
  • Gunasekera RS; Department of Chemistry, Physics, and Engineering, Biola University, La Mirada, CA, United States.
Front Med (Lausanne) ; 7: 589060, 2020.
Article in English | MEDLINE | ID: covidwho-1000101
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Prognostic study Language: English Journal: Front Med (Lausanne) Year: 2020 Document Type: Article Affiliation country: Fmed.2020.589060

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Prognostic study Language: English Journal: Front Med (Lausanne) Year: 2020 Document Type: Article Affiliation country: Fmed.2020.589060