Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2021; 27(23): 3208-3222
Published online Jun 21, 2021. doi: 10.3748/wjg.v27.i23.3208
COVID-19-associated diarrhea
Klara Megyeri, Áron Dernovics, Zaid I I Al-Luhaibi, András Rosztóczy
Klara Megyeri, Áron Dernovics, Zaid I I Al-Luhaibi, Department of Medical Microbiology and Immunobiology, University of Szeged, Szeged 6720, Csongrad, Hungary
András Rosztóczy, Division of Gastroenterology, Department of Internal Medicine, University of Szeged, Szeged 6720, Csongrad, Hungary
Author contributions: Megyeri K and Rosztóczy A made contributions to the concept and were involved in writing of the manuscript; Dernovics Á was involved in writing of the manuscript and creating the image; Al-Luhaibi ZII was involved in writing of the manuscript; all authors approved the final version of the article.
Supported by Stipendium Hungaricum Program, No. 109162 (to Al-Luhaibi ZII).
Conflict-of-interest statement: Authors declare no conflict of interests 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Klara Megyeri, MD, PhD, Associate Professor, Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm tér 10, Szeged 6720, Csongrad, Hungary. megyeri.klara@med.u-szeged.hu
Received: January 28, 2021
Peer-review started: January 29, 2021
First decision: March 6, 2021
Revised: March 19, 2021
Accepted: May 20, 2021
Article in press: May 20, 2021
Published online: June 21, 2021
Processing time: 133 Days and 13.4 Hours
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as a highly virulent respiratory pathogen that is known as the causative agent of coronavirus disease 2019 (COVID-19). Diarrhea is a common early symptom in a significant proportion of patients with SARS-CoV-2 infection. SARS-CoV-2 can infect and replicate in esophageal cells and enterocytes, leading to direct damage to the intestinal epithelium. The infection decreases the level of angiotensin-converting enzyme 2 receptors, thereby altering the composition of the gut microbiota. SARS-CoV-2 elicits a cytokine storm, which contributes to gastrointestinal inflammation. The direct cytopathic effects of SARS-CoV-2, gut dysbiosis, and aberrant immune response result in increased intestinal permeability, which may exacerbate existing symptoms and worsen the prognosis. By exploring the elements of pathogenesis, several therapeutic options have emerged for the treatment of COVID-19 patients, such as biologics and biotherapeutic agents. However, the presence of SARS-CoV-2 in the feces may facilitate the spread of COVID-19 through fecal-oral transmission and contaminate the environment. Thus gastrointestinal SARS-CoV-2 infection has important epidemiological significance. The development of new therapeutic and preventive options is necessary to treat and restrict the spread of this severe and widespread infection more effectively. Therefore, we summarize the key elements involved in the pathogenesis and the epidemiology of COVID-19-associated diarrhea.

Keywords: COVID-19; Diarrhea; Ionic imbalance; Viroporin; Angiotensin-converting enzyme type 2; Leaky gut

Core Tip: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in enterocytes, triggers ionic imbalances, activates the NLRP3 inflammasome pathway, induces apoptosis, and exerts a dual effect on the autophagic process. These effects of SARS-CoV-2 lead to the development of leaky gut. Increased permeability triggers the absorption of lipopolysaccharide into the circulation, further exacerbating inflammation induced by viral infection. In addition to drugs that affect the inflammatory response and viral replication, agents targeting autophagy and apoptosis appear to be potentially suitable for the treatment of coronavirus disease 2019 (COVID-19). The fecal-oral route of SARS-CoV-2 transmission calls for strict and more consistent adherence to hygiene rules to prevent the spread of COVID-19.