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

Figure 1 Pulmonary and extrapulmonary manifestations of coronavirus disease 2019. ARDS: Acute respiratory distress syndrome; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase. Headache and urticaria spelled wrongly.

Figure 2 Mechanisms and manifestations of coronavirus disease 2019 in the gut and liver. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ACE2: Angiotensin-converting enzyme 2; GIT: gastrointestinal tract; ADE: Antibody-dependent enhancement of infection; SIRS: Systemic inflammatory response syndrome; I/R: Ischemia and hypoxia reperfusion injury.

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.

Figure 4 Facial blackness and dull skin after coronavirus disease 2019 recovery. Three possible mechanisms are shown: (1) Iron in the damaged liver drains into blood vessels. Blood with high iron levels can lead to blackening of the face when it supplies the facial skin; (2) Estrogen cannot be metabolized in the damaged liver. Thus, elevated estrogen in the blood enhances the conversion of tyrosine to melanin; and (3) When liver function is impaired, adrenocortical function is hypoactive, and melanocyte-stimulating hormone increases resulting in an elevation in the secretion of melanin. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; MSH: Melanocyte-stimulating hormone; COVID-19: Coronavirus disease 2019.

Figure 5 Mechanisms of liver injury in patients with coronavirus disease 2019. (1) Angiotensin-converting enzyme 2-mediated targeting of cholangiocytes; (2) Antibody-dependent enhancement of infection; (3) Systemic inflammatory response syndrome and cytokine storms; and (4) Drug-induced liver injury. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ACE2: Angiotensin-converting enzyme 2; ADE: Antibody-dependent enhancement of infection; SIRS: Systemic inflammatory response syndrome; ARDS: Acute respiratory distress syndrome; IFN-γ: Interferon-γ; IL-6: Interleukin-6; IL-18: Interleukin-18; TNF-α; Tumor necrosis factor-α; ROS: Reactive oxygen species; ATP: Adenosine triphosphate.