Pathogenesis and Mechanism of Gastrointestinal Infection With COVID-19

Abstract

As a new infectious disease, COVID-19 is spread through the respiratory tract in most cases. Its source and pathological mechanism are not clear. The most common clinical feature is pulmonary infection. Also, a lot patients have gastrointestinal symptoms. Angiotensin-converting enzyme 2 (ACE2) is a functional cellular receptor for SARS-CoV-2, which is like SARS-CoV, a coronavirus associated with severe acute respiratory syndrome (SARS) outbreak in 2003. The tissues and cells expressing ACE2 are potential targets for SARS-CoV-2 infection, and the high expression of ACE2 in intestinal epithelial cells marks that SARS-CoV-2 may directly infect intestinal epithelial cells. Recent studies also suggest that SARS-CoV-2 existed and replicated in intestinal environment for a long time. The interaction between SARS-CoV-2 and RAS system leads to the decrease of local anti-inflammatory ability. The virus cycle leads to excessive imbalance of immune response and cytokine release. The downregulation of ACE2 after viral infection leads to gastrointestinal dysfunction. The above are the causes of gastrointestinal symptoms. Here, we reviewed the possible causes and mechanisms of gastrointestinal symptoms caused by COVID-19. Additionally, we discussed the influence of gastrointestinal symptoms on the prognosis of patients.

Malnutrition Increases Hospital Length of Stay and Mortality among Adult Inpatients with COVID-19

“…During the COVID-19 pandemic, individuals infected with symptomatic SARS-CoV-2 infection may experience nutritional compromise, impaired immunity and their ability to mitigate the viral illness [ 10 , 46 ]. The hypermetabolic response to SARS-CoV-2 infection can include fever, tachycardia, tachypnea, and cytokine storm that increase resting energy expenditure, caloric and micronutrient requirements.…”

“…The COVID-19 pandemic has heightened the risks of sarcopenia and protein-calorie malnutrition due to restrictions in physical activity from lockdowns, inaccessibility to exercise facilities, limited public transportation, and food insecurity from supply chain disruptions [ 9 ]. Symptomatic infection by SARS-CoV-2 results in a catabolic inflammatory response coupled with inherent physical immobility, poor nutrient intake from dysgeusia and anosmia, and frequent gastrointestinal involvement [ 10 ]. Collectively, acute symptomatic SARS-CoV-2 infections deplete lean body mass and vital micronutrients, which may further impair immunity and heighten COVID-19 disease severity.…”

Hallmarks of Severe COVID-19 Pathogenesis: A Pas de Deux Between Viral and Host Factors

“…Intestinal barrier disruption during SARS-CoV-2 infection might be explained by several mechanisms: a direct viral infection of intestinal epithelial cells (238); down-regulation of ACE2 after viral infection of enterocytes (239); systemic inflammation sustained by cytokine storm (226); IL-6mediated vascular damage (240); intestinal inflammation sustained by gut homing of T cells, as suggested by high plasma levels of CCL25, a gut homing marker, ligand for the chemokine receptor CCR9 (234,241), and gut dysbiosis with subsequent mucosal inflammation (226,242). The resulting increase in gut barrier permeability facilitates the passage of microbes and microbial products from the gut to the bloodstream, thus boosting systemic inflammation, which in turn promotes further gut leakiness, fostering a proinflammatory vicious cycle that can ultimately contribute to COVID-19 severity.…”

“…It has been hypothesized that down-regulation of ACE2 on SARS-CoV-2-infected enterocytes could be the link between COVID-19 and gut dysbiosis (239). Indeed, it is known that ACE2 down-regulation in small intestine epithelial cells reduces the expression of the sodium-dependent neutral amino acid transporter B (0)AT1 (253), which in turn disturbs tryptophan absorption.…”

Intestinal Damage in COVID-19: SARS-CoV-2 Infection and Intestinal Thrombosis

“…Secondly, SARS-CoV-2, as an enveloped virus, is largely unable to withstand the detergent effect of bile salts and the activity of digestive enzymes in the duodenum ( Figure 1 ). Although some studies have suggested that highly viscous mucus in the gastrointestinal tract protects SARS-CoV-2, allowing the virus to retain its infectivity ( Guo et al, 2021 ; Zhang H. et al, 2021 ), there is still a lack of direct evidence. Bushman et al (2019) had previously investigated the links between the structures of viruses and routes of transmission and found a strong association between fecal–oral transmission and the absence of a lipid envelope.…”