Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2021; 27(19): 2341-2352
Published online May 21, 2021. doi: 10.3748/wjg.v27.i19.2341
Pathophysiological mechanisms underlying gastrointestinal symptoms in patients with COVID-19
Byungchang Jin, Rajan Singh, Se Eun Ha, Hannah Zogg, Paul J Park, Seungil Ro
Byungchang Jin, Rajan Singh, Se Eun Ha, Hannah Zogg, Seungil Ro, Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, United States
Paul J Park, Department of Medicine, Renown Health, Reno, NV 89557, United States
Author contributions: Jin B, Singh R and Ro S conceived the study; Jin B and Singh R drafted the original manuscript and are joint first authors; Jin B, Singh R, Ha SE, Zogg H, Park PJ, and Ro S revised the manuscript and approved the submitted version.
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential 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: Seungil Ro, PhD, Associate Professor, Department of Physiology and Cell Biology, University of Nevada School of Medicine, Building L-207E, 1664 North Virginia Street, Reno, NV 89557, United States.
Received: January 29, 2021
Peer-review started: January 29, 2021
First decision: March 6, 2021
Revised: March 17, 2021
Accepted: April 22, 2021
Article in press: April 22, 2021
Published online: May 21, 2021

Gastrointestinal (GI) symptoms, such as diarrhea, abdominal pain, vomiting, and anorexia, are frequently observed in patients with coronavirus disease 2019 (COVID-19). However, the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain elusive. Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2 (ACE2) receptors resulting in impaired barrier function. While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1, the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function. Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses. Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea. The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI. Interestingly, the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation, a hallmark of functional GI disorders. Moreover, the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus, suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract, further indicating fecal-oral transmission as another important route of viral spread. This review summarized the evidence for pathophysiological mechanisms (impaired barrier function, gut inflammation, altered serotonin metabolism and gut microbiota dysbiosis) underlying the GI symptoms in patients with COVID-19.

Keywords: COVID-19, Gastrointestinal symptoms, Gut microbiota dysbiosis, Impaired barrier function, Serotonin, Angiotensin converting enzyme 2 receptor

Core Tip: Since the declaration of the pandemic on March 11, 2020 by the World Health Organization, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has quickly become a global health threat. In addition to respiratory symptoms, gastrointestinal (GI) symptoms have been widely observed in coronavirus disease 2019 (COVID-19) patients. Here, we have summarized the GI symptoms seen in COVID-19 patients that have been reported in nineteen studies and recapitulated potential mechanisms that are responsible for the GI symptoms in COVID-19 patients. This biochemical understanding may assist in new therapeutic approaches.