Pathogenesis of gastrointestinal symptoms
Intestinal involvement has many reasons. The
angiotensin-converting-enzyme 2 receptor (ACE-2) and transmembrane
protease, serine 2 (TMPRSS2), are key proteins in the cellular entry
process of the virus. The co-expression of these two proteins in the
same cell is essential for the entry of SARS-CoV-2.13Like the type II alveolar cells in the lung, the glandular cells of the
gastric, duodenal and rectal epithelium, and the enterocytes of the
ileum and colon can express both proteins at a high level. The
esophageal epithelium expresses ACE-2 at a lower level. ACE-2 is also
expressed on the surface of hepatocytes, and to a greater extent, on the
surface of cholangiocytes.
Although the specific mechanisms involved in diarrhea’s pathogenesis are
not fully understood, the infection is likely to alter intestinal
permeability, with malabsorption by enterocytes. Furthermore, ACE-2 has
been proposed to be involved in the absorption of dietary amino acids,
regulating the expression of antimicrobial peptides, and promoting
homeostasis of the intestinal microbiome. The mouse model know-out for
ACE-2 frequently develop colitis subsequently to SARS-CovV-2 infection,
suggesting that the virus may cause enzymatic changes, increased
susceptibility to intestinal inflammation and diarrhea.
Further studies are needed to clarify the mechanisms underlying diarrhea
and to define the correlation between respiratory and gastrointestinal
symptoms. The virus also appears to alter the intestinal microbiome even
when only the respiratory mucosa is involved through the regulation of
the mucosal immune system (the ”gut-lung axis”).4