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ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle.
Front Physiol. 2020; 11:574753.FP

Abstract

Engulfed by the grave consequences of the coronavirus disease 2019 (COVID-19) pandemic, a better understanding of the unique pattern of viral invasion and virulence is of utmost importance. Angiotensin (Ang)-converting enzyme (ACE) 2 is a key component in COVID-19 infection. Expressed on cell membranes in target pulmonary and intestinal host cells, ACE2 serves as an anchor for initial viral homing, binding to COVID-19 spike-protein domains to enable viral entry into cells and subsequent replication. Viral attachment is facilitated by a multiplicity of membranal and circulating proteases that further uncover attachment loci. Inherent or acquired enhancement of membrane ACE2 expression, likely leads to a higher degree of infection and may explain the predisposition to severe disease among males, diabetics, or patients with respiratory or cardiac diseases. Additionally, once attached, viral intracellular translocation and replication leads to depletion of membranal ACE2 through degradation and shedding. ACE2 generates Ang 1-7, which serves a critical role in counterbalancing the vasoconstrictive, pro-inflammatory, and pro-coagulant effects of ACE-induced Ang II. Therefore, Ang 1-7 may decline in tissues infected by COVID-19, leading to unopposed deleterious outcomes of Ang II. This likely leads to microcirculatory derangement with endothelial damage, profound inflammation, and coagulopathy that characterize the more severe clinical manifestations of COVID-19 infection. Our understanding of COVID-ACE2 associations is incomplete, and some conceptual formulations are currently speculative, leading to controversies over issues such as the usage of ACE inhibitors or Ang-receptor blockers (ARBs). This highlights the importance of focusing on ACE2 physiology in the evaluation and management of COVID-19 disease.

Authors+Show Affiliations

Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Laboratory Medicine, Rambam Medical Center, Haifa, Israel.Department of Clinical Biochemistry Hadassah Medical Center, Hadassah Hebrew University Hospital, Mt. Scopus, Jerusalem, Israel.Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.Department of Nephrology, Nazareth Hospital, EMMS, Nazareth and Azrieli Faculty of Medicine in Safed, Safed, Israel.The Bar-Ilan University Azrieli Faculty of Medicine in Safed, Safed, Israel.Department of Medicine, Hadassah Hebrew University Hospital, Mt. Scopus, Jerusalem, Israel.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33123031

Citation

Abassi, Zaid, et al. "ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle." Frontiers in Physiology, vol. 11, 2020, p. 574753.
Abassi Z, Higazi AAR, Kinaneh S, et al. ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle. Front Physiol. 2020;11:574753.
Abassi, Z., Higazi, A. A. R., Kinaneh, S., Armaly, Z., Skorecki, K., & Heyman, S. N. (2020). ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle. Frontiers in Physiology, 11, 574753. https://doi.org/10.3389/fphys.2020.574753
Abassi Z, et al. ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle. Front Physiol. 2020;11:574753. PubMed PMID: 33123031.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle. AU - Abassi,Zaid, AU - Higazi,Abd Al Roof, AU - Kinaneh,Safa, AU - Armaly,Zaher, AU - Skorecki,Karl, AU - Heyman,Samuel N, Y1 - 2020/10/06/ PY - 2020/06/21/received PY - 2020/09/09/accepted PY - 2020/10/30/entrez PY - 2020/10/31/pubmed PY - 2020/10/31/medline KW - COVID-19 pandemic KW - RAS inhibition KW - SARS-CoV-2 KW - angiotensin converting enzyme 2 KW - coagulopathy KW - inflammation SP - 574753 EP - 574753 JF - Frontiers in physiology JO - Front Physiol VL - 11 N2 - Engulfed by the grave consequences of the coronavirus disease 2019 (COVID-19) pandemic, a better understanding of the unique pattern of viral invasion and virulence is of utmost importance. Angiotensin (Ang)-converting enzyme (ACE) 2 is a key component in COVID-19 infection. Expressed on cell membranes in target pulmonary and intestinal host cells, ACE2 serves as an anchor for initial viral homing, binding to COVID-19 spike-protein domains to enable viral entry into cells and subsequent replication. Viral attachment is facilitated by a multiplicity of membranal and circulating proteases that further uncover attachment loci. Inherent or acquired enhancement of membrane ACE2 expression, likely leads to a higher degree of infection and may explain the predisposition to severe disease among males, diabetics, or patients with respiratory or cardiac diseases. Additionally, once attached, viral intracellular translocation and replication leads to depletion of membranal ACE2 through degradation and shedding. ACE2 generates Ang 1-7, which serves a critical role in counterbalancing the vasoconstrictive, pro-inflammatory, and pro-coagulant effects of ACE-induced Ang II. Therefore, Ang 1-7 may decline in tissues infected by COVID-19, leading to unopposed deleterious outcomes of Ang II. This likely leads to microcirculatory derangement with endothelial damage, profound inflammation, and coagulopathy that characterize the more severe clinical manifestations of COVID-19 infection. Our understanding of COVID-ACE2 associations is incomplete, and some conceptual formulations are currently speculative, leading to controversies over issues such as the usage of ACE inhibitors or Ang-receptor blockers (ARBs). This highlights the importance of focusing on ACE2 physiology in the evaluation and management of COVID-19 disease. SN - 1664-042X UR - https://www.unboundmedicine.com/medline/citation/33123031/ACE2_COVID_19_Infection_Inflammation_and_Coagulopathy:_Missing_Pieces_in_the_Puzzle_ L2 - https://doi.org/10.3389/fphys.2020.574753 DB - PRIME DP - Unbound Medicine ER -
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