Tsounis EP, Triantos C, Konstantakis C, Marangos M, Assimakopoulos SF. Intestinal barrier dysfunction as a key driver of severe COVID-19. World J Virol 2023; 12(2): 68-90 [PMID: 37033148 DOI: 10.5501/wjv.v12.i2.68]
Corresponding Author of This Article
Stelios F Assimakopoulos, MD, PhD, Associate Professor, Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, Rion, Patras 26504, Greece. sassim@upatras.gr
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Virol. Mar 25, 2023; 12(2): 68-90 Published online Mar 25, 2023. doi: 10.5501/wjv.v12.i2.68
Intestinal barrier dysfunction as a key driver of severe COVID-19
Efthymios P Tsounis, Christos Triantos, Christos Konstantakis, Markos Marangos, Stelios F Assimakopoulos
Efthymios P Tsounis, Christos Triantos, Christos Konstantakis, Division of Gastroenterology, Department of Internal Medicine, Medical School, University Hospital of Patras, Patras 26504, Greece
Markos Marangos, Stelios F Assimakopoulos, Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, Patras 26504, Greece
Author contributions: Assimakopoulos SF conceived and designed the review; Tsounis PE was responsible for the literature review and for drafting the manuscript; Triantos C, Konstantakis C, Marangos M, and Assimakopoulos SF were responsible for the revision of the manuscript for important intellectual content; all authors provided final approval for the version to be submitted.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Stelios F Assimakopoulos, MD, PhD, Associate Professor, Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, Rion, Patras 26504, Greece. sassim@upatras.gr
Received: October 12, 2022 Peer-review started: October 12, 2022 First decision: November 3, 2022 Revised: November 8, 2022 Accepted: January 16, 2023 Article in press: January 16, 2023 Published online: March 25, 2023
Core Tip
Core Tip: Severe coronavirus disease 2019 (COVID-19) is associated with a multi-layered disruption of gut barrier integrity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inflicts direct cytopathic or indirect immune-mediated injury to intestinal epithelial and endothelial cells and enhances paracellular permeability by downregulating tight junction proteins. SARS-CoV-2 induces profound gut microbiome alterations accompanied by dysregulation of mucosal immune responses. Gut dysbiosis attenuates, through the gut-lung axis, the ability of the respiratory immune system to elicit vigorous responses to contain SARS-CoV-2. Additionally, intestinal barrier dysfunction promotes endothelial activation and predisposes to detrimental COVID-19-related thrombotic complications. Finally, bacterial translocation and endotoxemia contribute to over-exuberant immune responses and hyper-inflammation in severe COVID-19.
