Gastrointestinal and hepatic diseases during the COVID-19 pandemic: Manifestations, mechanism and management

Figure 3 Mechanism of gastrointestinal symptoms in patients with coronavirus disease 2019. (1) Gut-lung axis: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds with angiotensin-converting enzyme 2 (ACE2) to enter the lung, which leads to the accumulation of angiotensin II (ANG II) and the reduction of Angiotensin (1-7). ANG II combined with angiotensin 1 receptor stimulates cytokine release and causes an upsurge of C-C chemokine receptor type 9 (CCR9) CD4T cells. Chemokine (C-C motif) ligand 25 subsequently enhances the recruitment of CCR9 CD4T cells into the small intestine. The changing flora then stimulates the polarization of T helper 17 cells, and eventually, interleukin 17A induces the recruitment of neutrophils. Cytokines and intestinal bacteria also enter the lung through the bloodstream, further affecting lung inflammation; and (2) Gut-liver axis: SARS-CoV-2 binds with ACE2 to enter the intestine, prevents absorption of the B0AT1/ACE2 transport pathway, and then decreases the stimulation of mammalian target of rapamycin to diminish the expression of antimicrobial peptides which result in gastrointestinal tract symptoms or enhanced ANG II that leads to the upregulation of tissue factor VIII, Von Willebrand factor, and plasminogen activator inhibitor-1 expression by endothelial cells resulting in mesenteric thrombosis. The intestinal flora, through the portal vein, is transferred to the liver, where it binds to toll-like receptors resulting in hepatitis. Additionally, the liver, can transport metabolites to the intestine via the biliary tract,. COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ACE2: Angiotensin-converting enzyme 2: ANG II: Angiotensin II; Ang1–7: Angiotensin (1-7); AT1R: Angiotensin 1 receptor; CCR9: C-C chemokine receptor type 9; CCL25: Chemokine (C-C motif) ligand 25; Th17: T helper 17; IL-17: Interleukin 17; PMNS: Polymorphonuclear neutrophils; B0AT1: Sodium-dependent neutral amino acid transporter; mTOR: Mammalian target of rapamycin; AMPs: Antimicrobial peptides; FVIII: Tissue factor VIII; VWF: Von Willebrand factor; PAI-1: Plasminogen activator inhibitor-1; TLR: Toll-like receptor.