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Review
. 2020 Oct-Dec;21(4):1470320320979097.
doi: 10.1177/1470320320979097.

Angiotensin-converting enzyme 2, the complement system, the kallikrein-kinin system, type-2 diabetes, interleukin-6, and their interactions regarding the complex COVID-19 pathophysiological crossroads

Martijn Hoevenaar  1 , Dolf Goossens  1 , Janne Roorda  2
Affiliations
Review

Angiotensin-converting enzyme 2, the complement system, the kallikrein-kinin system, type-2 diabetes, interleukin-6, and their interactions regarding the complex COVID-19 pathophysiological crossroads

Martijn Hoevenaar et al. J Renin Angiotensin Aldosterone Syst. 2020 Oct-Dec.

Abstract

Because of the current COVID-19-pandemic, the world is currently being held hostage in various lockdowns. ACE2 facilitates SARS-CoV-2 cell-entry, and is at the very center of several pathophysiological pathways regarding the RAAS, CS, KKS, T2DM, and IL-6. Their interactions with severe COVID-19 complications (e.g. ARDS and thrombosis), and potential therapeutic targets for pharmacological intervention, will be reviewed.

Keywords: COVID-19; angiotensin-converting enzyme 2; complement; diabetes; interleukin-6; kallikrein-kinin system; renin angiotensin aldosterone system; thrombosis.

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Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
ROS- and IL-6-mediated MAPK signaling and their effects regarding severe COVID-19 complications, for example, ARDS and thrombosis.
Figure 2.
Figure 2.
The CS including the COVID-19-induced lectin pathway feedback mechanism.
Figure 3.
Figure 3.
The trinity of systems: RAAS, CS, KKS, and their interconnections, as well as their interactions with IR, the coagulation pathway, inflammation, and COVID-19.
Figure 4.
Figure 4.
The RAAS, CS, KKS, IR, IL-6, and their interactions regarding severe COVID-19 complications, for example, ARDS and thrombosis, with ACE2 as master regulator.
See this image and copyright information in PMC

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