COVID-19 and gastrointestinal system: A brief review

Abstract

COVID-19 is a recent pandemic that is still a major health problem of modern times and already more than 17.5 lakhs people succumbed to this deadly disease. This disease is caused by novel coronavirus which is named SARS-COV-2 by the International Committee on Taxonomy of Viruses. This virus originated from Wuhan city in Hubei province of China in December 2019 and within a short period spread across the many countries in the globe. There are a lot of basic as well as clinical research is going on to study the mode of transmission and the mechanism of action of SARS-COV-2 infection and its therapeutics. SARS-COV-2 is not only known to infect lungs, but it also infects other organs in the human body including the gastrointestinal (GI) tract, the liver, and the pancreas via the angiotensin-converting enzyme (ACE) 2, an important component of the renin-angiotensin system. In this short review, we are mainly discussing the mode of SARS-COV-2 transmission, physiological counterbalancing roles of ACE2 and ACE and the tissue patterns of ACE2 expression, and the overall effect of COVID19 on human gastrointestinal System. Therefore, this review sheds light on the possible mechanism of SARS-COV-2 infection in the GI system and its pathological symptoms raising a potential possibility of GI tract acting as a secondary site for SARS-CoV-2 tropism and infection. Finally, future studies to understand the fecal-oral transmission of the virus and the correlation of viral load and severity of GI symptoms are proposed to gain knowledge of the GI symptoms in COVID-19 to aid in early diagnosis and prognosis.

Keywords: ACE2; COVID-19; Gastrointestinal system; SARS-COV-2; Virus.

Fig. 1

Schematic representation of the SARS-CoV-2. The major structural proteins of SARS-CoV-2 consists of a spike (S), membrane (M), and envelop proteins that are embedded in the lipid bilayers and nucleic capsid (N) proteins covering single-stranded RNA. The spike proteins of the SARS-CoV-2 for which they derived the name ‘corona’ are the key structures that attach to host cell receptor proteins angiotensin-converting enzyme 2 (ACE2). The S proteins consist of S1 and S2 subunits that attach to the ACE2 and the cell membrane, respectively. The membrane envelops a large single-stranded positive-sense RNA.

Fig. 2

Simplified scheme of the renin-angiotensin system, and ACE/AngII/AT1R and ACE2/Ang (1–7)/MasR pathways. A. Renin derived from kidney converts angiotensin to decapeptide angiotensin I (Ang I). Angiotensin-converting enzyme (ACE) converts Ang I to octapeptide angiotensin II (Ang II). ACE2 converts Ang II to a heptapeptide Ang (1–7). ACE2 also acts on Ang I to form Ang (1–9) which then yields Ang (1–7) upon further cleavage by ACE. B. The effects of Ang II are mediated via activation of its cognate G protein-coupled receptor AT1 (AT1R), whereas the effects of Ang (1–7) are mediated via activation of its cognate G protein-coupled Mas receptor (MasR). The ACE2/Ang1-7/MasR pathway acts as a counter-regulatory pathway to the ACE/Ang II/AT1R pathway. The effects of ACE/Ang II/AT1R pathway involves an increase in Ca²⁺ and activation of NAD(P)H oxidase, extracellular regulated kinase1/2 (ERK1/2), Jun kinase (JNK) and the transcription factor NF-κB. The effects of the ACE2/Ang (1–7)/MasR pathway involves an increase in nitric oxide (NO) formation, and activation of Akt and the phosphatase SHP-2 and the transcription factor FOXO1.

Fig. 3

Schematic diagram summarizing the role of ACE2/ANG-(1–7) in GI systems in normal physiology and presumably its involvement in SARS-CoV-2 infection. A. Physiologically, ACE2/Ang (1–7) mediates neutral amino acid transport and facilitates the release of antimicrobial peptides to decreases gut dysbiosis and prevent inflammation in the gastrointestinal (GI) tract, promotes insulin sensitivity and decrease fibrosis and steatosis in the liver, and promotes β cell growth and insulin secretion and decreases inflammation in the pancreas. B. Decrease in ACE2 function during SARS-Cov-2 infection may lead to an increase in Ang II and a decrease in Ang (1-) levels resulting in a decrease in neutral amino acid transport and an increase in gut dysbiosis and inflammation in the GI tract, decrease in insulin sensitivity and an increase in fibrosis and steatosis in the liver, and an increase in inflammation and decrease in β cell growth resulting in insulin secretion in the pancreas. A decrease in ACE2 expression and function of ACE2/Ang (1–7) may play a key role in the pathogenesis of SARS-CoV-2. A decrease in ACE2 expression and activity and loss of protective effects of ACE2/Ang (1–7) due to co-morbid conditions such as old-age, diabetes, liver diseases (e.g., NAFLD) and pancreatic inflammation may exacerbate the symptoms associated with SARS-CoV-2 infection. Arrows indicate an increase or a decrease.