COVID-19 and diarrhea: putative mechanisms and management

Abstract

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), has recently posed a threat to global health by spreading at a high rate and taking millions of lives worldwide. Along with the respiratory symptoms, there are gastrointestinal manifestations and one of the most common gastrointestinal symptoms is diarrhea which is seen in a significant percentage of COVID-19 patients.

Literature review: Several studies have shown the plausible correlation between overexpressed angiotensin converting enzyme 2 (ACE2) in enterocytes and SARS-CoV-2, as ACE2 is the only known receptor for the virus entry. Along with the dysregulated ACE2, there are other contributing factors such as gut microbiome dysbiosis, adverse effects of antiviral and antibiotics for treating infections and inflammatory response to SARS-CoV-2 which bring about increased permeability of gut cells and subsequent occurrence of diarrhea. Few studies found that the SARS-CoV-2 is capable of damaging liver cells too. No single effective treatment option is available.

Limitations: Confirmed pathophysiology is still unavailable. Studies regarding global population are also insufficient.

Conclusion: In this review, based on the previous works and literature, we summarized the putative molecular pathophysiology of COVID-19 associated diarrhea, concomitant complications and the standard practices of management of diarrhea and hepatic manifestations in international setups.

Keywords: Angiotensin-converting enzyme-2; Antibiotic-associated diarrhea; COVID-19; Diarrhea; Diarrhea management; SARS-CoV-2.

Figure 1

Partial mechanisms of COVID-19-associated diarrhea. SARS-CoV-2 binds to ACE2 receptor and the S protein of viral envelop is cleaved into S1 and S2 (1). Activated S2 leads to the fusion of viral membrane and host cell membrane (2 & 3). Entry of the virus into the host cell causes ionic imbalance in the host contributing to a leaky gut. This figure was partially adapted from ‘Mechanism of SARS-CoV-2 Viral Entry’ by BioRender.com (2022) and retrieved from https://app.biorender.com/biorender-templates. ACE2: Angiotensin-converting enzyme; CaCC: Ca²⁺ activated Cl⁻ Channel; CFTR: CF transmembrane conductance regulator; NHE3: Na⁺-H⁺ exchanger 3; S, spike.

Figure 2

Mechanisms involved in COVID-19-associated diarrhea. SARS-CoV-2 enters into a host cell by ACE2 receptor, where it disrupts the B₀AT/ACE2 absorption pathway and then interrupts the activation of mTOR resulting in the reduction of antimicrobial peptide production. Altogether, these affect the normal gut microbiome contributing to inflammatory cytokine production. This figure was partially generated by Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license. ACE2: angiotensin-converting enzyme; B₀AT, broad neutral amino acid transporter; mTOR, mammalian target of rapamycin.