Abstract
COVID-19 from SARS-CoV-2 has caused a large number of infections and deaths. COVID-19 is a respiratory infectious disease caused by the combination of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) receptor into the target organ of the host. COVID-19 patients not only have respiratory symptoms, but also some patients with symptoms such as nausea, abdominal pain, and diarrhea. Even a few patients have atypical symptoms such as diarrhea as the first manifestation, indicating that the severity of COVID-19 patients is closely related to gastrointestinal symptoms. There is currently rare researches on long-term gastrointestinal adverse impacts in patients with COVID-19. We will summarize the etiology, epidemiology and pathogenic mechanism of SARS-CoV-2 as well as the digestive system symptoms and targeted treatment of COVID-19, so as to increase the insight of the long-term gastrointestinal injury caused by SARS-CoV-2, thereby providing new therapeutic strategies and targets for gastrointestinal injury.
Supplementary materials
Title
Composition of gut microbiota in COVID-19 patients.
Description
SARS-CoV-2 exacerbates dysbiosis of multiple microbiota, which are associated with disease severity in COVID-19 patients
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Title
The schematic genomic structure of SARS-CoV-2.
Description
(A) Typical structure of SARS-CoV-2 exhibits various structural proteins, such as S, M, E, and N protein. (B) SARS-CoV-2 genome is single-stranded, with a 5'-caps and a 3' - UTR tails, which is approximately 30 kb. SARS-CoV-2 genome consists of four structural protein genes (spike, envelope, membrane and nucleocapsid genes), as well as accessory proteins (ORF 1a, ORF 1b,3a, 6, 7a, 7b, 8a, 9b and 10).
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Title
The role of ACE2 in renin-angiotensin system (RAS) and the down-regulation of ACE2 by SARS-CoV-2 on the membrane.
Description
Angiotensinogen is converted by renin to angiotensin I (Ang I). Ang I is subsequently converted by ACE to angiotensin II (Ang II), which binds to AT1R to play a role in releasing pro-inflammatory factors, and promoting fibrosis and vasoconstriction. ACE2 negatively regulates the function of ACE by converting Ang I to Ang (1-9) and Ang II to Ang (1-7), which has the effect on promoting vasodilation, anti-fibrosis, and anti-inflammatory. SARS-CoV-2 interacts with ACE2 and consumes a large amount of ACE2 in target organs, such as lung and intestine, resulting in the disorder of ACE2 and ACE. The downregulation of ACE2 leads to unopposed accumulation of Ang II, which may accelerate the progression of COVID-19.
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Title
SARS-CoV-2 infects intestinal epithelial cells. The RBD of SARS-CoV-2 S protein enhanced the ability to bind to ACE2 on intestinal cells.
Description
TMPRSS2 and furin promote RBD binding to ACE2 in IECs, thereby enhancing viral infection and causing gastrointestinal damage. After SARS-CoV-2 infects IECs, the immune system is in disorder, leading to the increase of pro-inflammatory cytokines, such as L-1β, IL-1RA, IL-6, IL-7, IL-8, IL-9, IL-10, IL-18, M-CSF, IFN-γ, PDGF, TNF-α and VEGF, which triggers cytokine storms. Infection of IECs by SARS-CoV-2 also leads to gut dysbiosis. The homeostasis of gut microbiota is related to the amino acid transport function of ACE2, which binds to the neutral amino acid transporter (B0AT1). Tryptophan, as a neutral amino acid, regulates the expression of antimicrobial peptides, which maintain the flora of small intestine and large intestine in a stable state. RBD, receptor binding domain; ACE2, angiotensin converting enzyme 2; TMPRSS2, transmembrane serine protease 2; DC, dendritic cell; M-CSF, macrophage colony-stimulating factor; PDGF, platelet derived growth factor; VEGF, vascular endothelial growth factor.
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Title
Composition of intestinal microbiota in healthy individuals and COVID-19 patients.
Description
Beneficial commensal bacteria such as Faecalibacterium prausnitzii, Eubacterium rectale, Bifidobacteria are dominant in the intestine of healthy population. However, the commensal symbionts are depleted, and opportunistic pathogens such as Coprobacillus, Clostridium ramosum and Clostridium hathewaii are significantly enriched in gut of COVID-19 patients. In addition, the intestinal microbiota is closely associated with SARS-CoV-2 load in COVID-19 patients. Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliansis and Bacteroides ovatus are negatively correlated with the viral load, whereas the abundance of Granulatella and Rothia mucilaginosa in oral and intestinal samples of COVID-19 patients is positively correlated with SARS-CoV-2 load.
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Title
Schematic mechanism of intestinal injury caused by SARS-CoV-2.
Description
The pathogenesis of intestinal injury in COVID-19 patients is related to the interaction between SARS-CoV-2 and ACE2, which destroys epithelial cells and leads to intestinal inflammation. In addition, cytokine storm, gut dysbiosis, psychosocial factors, the aggravation of primary diseases, and the side effects of antiviral drugs and antibiotics should not be ignored during the treatment of gastrointestinal injury in COVID-19 patients.
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