COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations

Abstract

Background: Since its first report in Wuhan, China, in December 2019, COVID-19 has become a pandemic, affecting millions of people worldwide. Although the virus primarily affects the respiratory tract, gastrointestinal symptoms are also common. The aim of this narrative review is to provide an overview of the pathophysiology and clinical manifestations of gastrointestinal COVID-19. Methods: We conducted a systematic electronic search of English literature up to January 2023 using Medline, Scopus, and the Cochrane Library, focusing on papers that analyzed the role of SARS-CoV-2 in the gastrointestinal tract. Results: Our review highlights that SARS-CoV-2 directly infects the gastrointestinal tract and can cause symptoms such as diarrhea, nausea/vomiting, abdominal pain, anorexia, loss of taste, and increased liver enzymes. These symptoms result from mucosal barrier damage, inflammation, and changes in the microbiota composition. The exact mechanism of how the virus overcomes the acid gastric environment and leads to the intestinal damage is still being studied. Conclusions: Although vaccination has increased the prevalence of less severe symptoms, the long-term interaction with SARS-CoV-2 remains a concern. Understanding the interplay between SARS-CoV-2 and the gastrointestinal tract is essential for future management of the virus.

Keywords: COVID-19; SARS-CoV-2; gastrointestinal tract; pathophysiology of COVID-19.

Figure 1

SARS-CoV-2 structure. SARS-CoV-2 is a single-stranded β-coronavirus. Two-thirds of viral RNA, in the first open reading frame (ORF 1a/b), encodes for 16 non-structural proteins (NSP). The remaining viral genome expresses accessory proteins, interfering with the host innate immune response, and four structural proteins (S, E, N, M).

Figure 2

Main entry route of SARS-CoV-2 in gastrointestinal tract. The spike protein of SARS-CoV-2 binds angiotensin-converting enzyme 2 (ACE2) receptors. Priming by TMPRSS2, TMPRSS4 (or other proteases such as FURIN) leads to endocytosis. The virus is uncoated, genomic RNA is released, and viral proteins are synthesized using the host replication system.

Figure 3

SARS-CoV-2–gastrointestinal tract interactions. SARS-CoV-2 infection induces a disruption of intestinal barrier integrity. Gut microbiota is altered with a reduction in microbial diversity, reduction in beneficial bacterial strains, and an increase in pathogens. The mechanical barrier, consisting of intestinal epithelial cells and tight junctions, is also affected by the infection. SARS-CoV-2 induces immune activation, resulting in increased levels of cytokines and leukocytes.

Figure 4

Gut microbiome alterations in COVID-19. In healthy individuals, Faecalibacterium prausnitzii, Eubacterium and Roseburia are the prevalent strains of gut microbiome. These bacteria show anti-inflammatory properties and produce SCFA. In patients affected by COVID-19, a depletion of symbionts and an increase in opportunistic pathogens were described. Gut dysbiosis observed during COVID-19 infection persists after SARS-CoV-2 clearance.