SARS-CoV-2 and the Gut: From Viral Persistence to Post-Infectious Gut–Brain Disorders

COVID-19 is a multisystem disease with important gastrointestinal (GI) involvement. Diarrhea, nausea or vomiting, reduced appetite, and abdominal pain are among the most frequently reported GI manifestations during acute infection, although their prevalence varies across populations, viral variants, disease severity, and study designs. The biological basis of intestinal involvement is supported by the expression of angiotensin-converting enzyme 2 (ACE2) and host proteases required for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into intestinal epithelial cells. Viral RNA and antigens have also been detected in intestinal tissues after respiratory clearance, indicating persistence of viral material in some individuals; these findings do not by themselves demonstrate replication-competent virus. Uncommon but potentially severe GI complications include acute mesenteric ischemia, ischemic colitis, gastrointestinal bleeding, ileus, intestinal perforation, and acute pancreatitis. Although COVID-19 is associated with worse outcomes in acute pancreatitis, direct viral causation remains uncertain. Persistent GI manifestations have also emerged as an important component of post-COVID disease. Studies using Rome criteria have identified new-onset disorders of gut–brain interaction, including irritable bowel syndrome, functional dyspepsia, functional diarrhea, and functional constipation. Candidate mechanisms include intestinal viral antigen persistence, epithelial barrier dysfunction, sustained immune activation, gut microbial dysbiosis, and altered tryptophan–serotonin signaling; most links remain associative rather than causally established. Altered microbial signaling may also contribute to mucosal inflammation and disturbances in gut–lung and gut–brain communication. Overall, current evidence supports GI involvement in both acute and post-acute COVID-19. Further studies integrating microbiome, metabolic, and immune profiling are needed to clarify the mechanisms underlying post-COVID GI disorders and identify potential biomarkers and therapeutic targets.