ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle

Zaid Abassi, Abd Al Roof Higazi, Safa Kinaneh, Zaher Armaly, Karl Skorecki, Samuel N. Heyman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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.

Original languageEnglish
Article number574753
JournalFrontiers in Physiology
StatePublished - 6 Oct 2020

Bibliographical note

Funding Information:
ZAb acknowledges research support from the Israel Science Foundation Grant 544/18.

Publisher Copyright:
© Copyright © 2020 Abassi, Higazi, Kinaneh, Armaly, Skorecki and Heyman.


  • COVID-19 pandemic
  • RAS inhibition
  • SARS-CoV-2
  • angiotensin converting enzyme 2
  • coagulopathy
  • inflammation


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