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World J Diabetes. May 15, 2021; 12(5): 590-602
Published online May 15, 2021. doi: 10.4239/wjd.v12.i5.590
Advanced-glycation end-products axis: A contributor to the risk of severe illness from COVID-19 in diabetes patients
Armando Rojas, Cristian Lindner, Ileana Gonzàlez, Miguel Angel Morales
Armando Rojas, Ileana Gonzàlez, Biomedical Research Labs, Medicine Faculty, Catholic University of Maule, Talca 3460000, Chile
Cristian Lindner, Medicine Faculty, Catholic University of Maule, Talca 3460000, Chile
Miguel Angel Morales, Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Santiago 8320000, Chile
Author contributions: All authors contributed to the original ideas and writing of this paper; Rojas A designed the report and wrote the paper; Lindner C contributed to data collection, draft manuscript preparation, and art-work; Gonzàlez I and Morales MA contributed to data acquisition, drafting, and revising the manuscript.
Conflict-of-interest statement: None of the authors declare a conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Armando Rojas, PhD, Full Professor, Biomedical Research Labs, Medicine Faculty, Catholic University of Maule, 3605 San Miguel Avenue, Talca 3605, Chile. arojasr@ucm.cl
Received: January 4, 2021
Peer-review started: January 4, 2021
First decision: January 25, 2021
Revised: January 29, 2021
Accepted: April 7, 2021
Article in press: April 7, 2021
Published online: May 15, 2021
Processing time: 121 Days and 21.6 Hours
Abstract

Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial role of the receptor for advanced-glycation end-products (RAGE) in orchestrating a plethora of proinflammatory cellular responses leading to many of the complications and end-organ damages reported in patients with diabetes mellitus (DM). During the coronavirus disease 2019 (COVID-19) pandemic, many clinical reports have pointed out that DM increases the risk of COVID-19 complications, hospitalization requirements, as well as the overall severe acute respiratory syndrome coronavirus 2 case-fatality rate. In the present review, we intend to focus on how the basal activation state of the RAGE axis in common preexisting conditions in DM patients such as endothelial dysfunction and hyperglycemia-related prothrombotic phenotype, as well as the contribution of RAGE signaling in lung inflammation, may then lead to the increased mortality risk of COVID-19 in these patients. Additionally, the cross-talk between the RAGE axis with either another severe acute respiratory syndrome coronavirus 2 receptor molecule different of angiotensin-converting enzyme 2 or the renin-angiotensin system imbalance produced by viral infection, as well as the role of this multi-ligand receptor on the obesity-associated low-grade inflammation in the higher risk for severe illness reported in diabetes patients with COVID-19, are also discussed.

Keywords: COVID-19; Diabetes mellitus; Advanced glycation; Alarmins; Advanced-glycation end-products axis; Inflammation

Core Tip: Compelling evidence support that diabetes mellitus increases the risk of coronavirus disease 2019 (COVID-19) complications, as well as the overall syndrome coronavirus 2 case-fatality. Different reports have suggested the putative involvement of several molecular mechanisms underlying this increased risk. We herein discuss the contribution of the activation of the receptor for advanced-glycation end-products axis to the higher risk for severe illness reported in diabetes patients with COVID-19.