Intestinal Damage, Inflammation and Microbiota Alteration during COVID-19 Infection

Abstract

Background: The virus SARS-CoV-2 is responsible for respiratory disorders due to the fact that it mainly infects the respiratory tract using the Angiotensin-converting enzyme 2 (ACE2) receptors. ACE2 receptors are also highly expressed on intestinal cells, representing an important site of entry for the virus in the gut. Literature studies underlined that the virus infects and replicates in the gut epithelial cells, causing gastrointestinal symptoms such as diarrhea, abdominal pain, nausea/vomiting and anorexia. Moreover, the SARS-CoV-2 virus settles into the bloodstream, hyperactivating the platelets and cytokine storms and causing gut–blood barrier damage with an alteration of the gut microbiota, intestinal cell injury, intestinal vessel thrombosis leading to malabsorption, malnutrition, an increasing disease severity and mortality with short and long-period sequelae. Conclusion: This review summarizes the data on how SARS-CoV-2 effects on the gastrointestinal systems, including the mechanisms of inflammation, relationship with the gut microbiota, endoscopic patterns, and the role of fecal calprotectin, confirming the importance of the digestive system in clinical practice for the diagnosis and follow-up of SARS-CoV-2 infection.

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID‐19

“…The cause of gastrointestinal reaction caused by SARS‐CoV‐2 virus may be related to angiotensin‐converting enzyme 2 (ACE2) receptor binding. ACE2 receptors are highly expressed in intestinal cells (e.g., small intestine epithelial cells and large intestine epithelial cells) and are the main route by which viruses enter the intestine 47 . In addition, severe COVID‐19 patients often have gastrointestinal complications such as ileus, gastrointestinal bleeding, intestinal ischemia, and even intestinal perforation 48 .…”

“…ACE2 receptors are highly expressed in intestinal cells (e.g., small intestine epithelial cells and large intestine epithelial cells) and are the main route by which viruses enter the intestine. 47 In addition, severe COVID‐19 patients often have gastrointestinal complications such as ileus, gastrointestinal bleeding, intestinal ischemia, and even intestinal perforation. 48 Fecal calprotectin is often considered to be an indicator associated with intestinal inflammation, and its most important use is in the differential diagnosis of inflammatory bowel diseases (IBD) and irritable bowel syndrome.…”

Small Bowel Diverticulosis and COVID-19: Awareness Is the Key: A Case Series and Review of the Literature

“…A comprehensive patient history must be obtained to rule out other conditions such as appendicitis, cholecystitis, colonic diverticulitis, pancreatitis, bowel obstruction, or foreign body perforation [3,4,[8][9][10][11][12][13][14][15][16][17][18][19][20]24,34]. An abdominal X-ray can help detect perforation or obstruction but cannot establish a diagnosis on its own.…”

Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

“…Numerous symptoms may accompany the severity of the disease. 77 The imbalance in gut microbiota may also be related to the imbalance in metabolite level, while the resulting inflammatory cytokine storm can cause overall immune disorders in the body. Viruses can easily invade the intestinal tract because of the high ACE2 expression in lung tissue and intestinal epithelial cells.…”

“…Disorder of intestinal flora destroys the gut–blood barrier and triggers immune activation, which is associated with systemic symptoms. 77 Multiomics association analysis revealed a potential regulatory relationship between intestinal flora and metabolites such as branched‐chain amino acids and the chemotactic response of inflammatory factors in patients with COVID‐19, and the intestinal flora may regulate lung and brain functions through metabolites. The severity of COVID‐19 is partly associated with host immune dysregulation, and Mendelian randomization studies have suggested that the gut microbiota is associated with susceptibility, hospitalization rate, and severity.…”