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World J Gastroenterol. Jan 21, 2022; 28(3): 275-289
Published online Jan 21, 2022. doi: 10.3748/wjg.v28.i3.275
Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs
Andrzej S Tarnawski, Amrita Ahluwalia
Andrzej S Tarnawski, Gastroenterology Research Department, University of California Irvine and the Veterans Administration Long Beach Healthcare System, Long Beach, CA 90822, United States
Amrita Ahluwalia, Research Service, Veterans Administration Long Beach Healthcare System, Long Beach, CA 90822, United States
Author contributions: Ahluwalia A and Tarnawski AS designed the overall concept, outline of the manuscript, and contributed to the writing and editing of the manuscript, illustrations, and review of literature, and approved the final version of manuscript. Ahluwalia A ( and Tarnawski AS ( are co-corresponding authors.
Conflict-of-interest statement: No 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:
Corresponding author: Amrita Ahluwalia, PhD, Research Scientist, Research Service, Veterans Administration Long Beach Healthcare System, 5901 E, Seventh Street, Long Beach, CA 90822, United States.
Received: November 15, 2021
Peer-review started: November 15, 2021
First decision: November 22, 2021
Revised: December 2, 2021
Accepted: January 11, 2022
Article in press: January 11, 2022
Published online: January 21, 2022

The coronavirus disease 2019 (COVID-19) infected so far over 250 million people and caused the death of over 5 million worldwide. Aging, diabetes, and cardiovascular diseases, conditions with preexisting impaired endothelial functions predispose to COVID-19. While respiratory epithelium is the main route of virus entry, the endothelial cells (ECs) lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 patients. COVID-19 not only affects the lungs and respiratory system but also gastrointestinal (GI) tract, liver, pancreas, kidneys, heart, brain, and skin. Blood vessels are likely conduits for the virus dissemination to these distant organs. Importantly, ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular network. The World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract, liver, pancreas, etc., however, the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury, spreading to various organs, and injury healing have not been sufficiently emphasized. In the present article, we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic, significant efficacy in controlling severe COVID-19 infection.

Keywords: Endothelial cells, Impaired endothelial function, Blood vessels, SARS-CoV-2, COVID-19, Cytokine storm

Core Tip: The coronavirus disease 2019 (COVID-19) pandemic has enormous health care and economic impact on the entire world - infecting more than 250 million people in 213 countries and territories, causing death of more than 5 million (as of November 1, 2021). We comment here on some outstanding papers on COVID-19 published in World Journal of Gastroenterology and reviewed the important role of endothelium and blood vessels in COVID-19 infection. Endothelial cells and blood vessels are both the targets and a conduit for the spread of severe acute respiratory syndrome coronavirus 2 and play a critical role in COVID-19-induced tissue injury and dissemination to various organs. Pre-existing endothelial impaired function could make endothelial cells more sensitive to COVID-19 or at least COVID-19-induced impairment might be synergistic with pre-existing impairment. That could be one contributing factor explaining why older or diabetic patients have more severe responses to infection, since these conditions are already impacted impaired endothelial function.