Gastrointestinal Involvement in SARS-CoV-2 Infection

Abstract

SARS-CoV-2 has evolved into a virus that primarily results in mild or asymptomatic disease, making its transmission more challenging to control. In addition to the respiratory tract, SARS-CoV-2 also infects the digestive tract. Some gastrointestinal symptoms occur with or before respiratory symptoms in patients with COVID-19. Respiratory infections are known to cause intestinal immune impairment and gastrointestinal symptoms. When the intestine is inflamed, cytokines affect the lung immune response and inflammation through blood circulation. The gastrointestinal microbiome may be a modifiable factor in determining the risk of SARS-CoV-2 infection and disease severity. The development of oral SARS-CoV-2 vaccine candidates and the maintenance of gut microbiota profiles may contribute to the early control of COVID-19 outbreaks. To this end, this review summarizes information on the gastrointestinal complications caused by SARS-CoV-2, SARS-CoV-2 infection, the gastrointestinal-lung axis immune response, potential control strategies for oral vaccine candidates and maintaining intestinal microbiota homeostasis.

Keywords: SARS-CoV-2; gastrointestinal involvement; microbiota; oral vaccine; prevention.

Figure 1

Gastrointestinal symptoms, bleeding, and mortality in patients with COVID-19. The 95% confidence interval (95% CI); random-effects model estimate. For the I² statistic, the level of heterogeneity was defined as low (25–50%), moderate (50–75%), or high (>75%). Squares indicate proportions. GI, gastrointestinal. References: Cheung et al., 2020 [9]; Marasco et al., 2021 [11]; Parasa et al., 2020 [7]; Shehab et al., 2021 [12].

Figure 2

Gastrointestinal symptoms described in patients with COVID-19. The 95% confidence interval (95% CI); random-effects model estimate. For the I² statistic, the level of heterogeneity was defined as low (25–50%), moderate (50–75%), or high (>75%). Squares indicate proportions. NA, not available. References: Bolia et al., 2021 [23]; Mao et al., 2020 [21]; Parasa et al., 2020 [7]; Shehab et al., 2021 [12]; Wang et al., 2021 [30]; Zarifian et al., 2021 [19]; Zeng et al., 2022 [20].

Figure 3

Multiple sequence alignment of the receptor-binding domains amino acid sequences of five SARS-CoV-2 variants. Contacting residues in the SARS-CoV-2 receptor-binding domain are indicated by an asterisk. The receptor-binding motif sequence is shown in red. The surface glycoprotein receptor-binding domain sequences are from GenBank, with the following accession protein ID: UFZ12739.1 (Alpha), QWW93436.1 (Beta), QWW27582.1 (Gamma), UAL04647.1 (Delta), and UKO09871.1 (Omicron).

Figure 4

mRNA expression of ACE2 in healthy human tissues. Source: BioProject: PRJEB4337.

Figure 5

Cytokine storm of the COVID-19 disease. G-SCF: plasma granulocyte colony-stimulating factor, IL: interleukin; IP: interferon-inducible protein; MCP-1: monocyte chemokine-1, MIP: macrophage inflammatory protein, TGF-β1: tumor growth factor-β1, TNF: tumor necrosis factor, VEGF: vascular endothelial growth factor.

Figure 6

Gastrointestinal-lung axis in COVID-19. ACE2, angiotensin-converting enzyme 2.