Figure 1.

Pathways of the gastrointestinal tract damage in HIV/SIV and SARS-CoV-2 infections. (A) Normal GI tract is a continuous barrier which protects the internal milieu by the damage of an enormous microbiota existent in the GI lumen. This barrier is multistratified, being represented by mucus, a continuous intestinal epithelium, and immune effectors that capture translocated microbes. (B) While HIV/SIV penetrates the body at mucosal sites, GI infection occurs through systemic seeding. CD4⁺ T cell destruction and the inflammatory responses contribute to the destruction of the mucosal barrier from within, leading to the translocation of the intestinal flora in the lamina propria and then systemically; (C) SARS-CoV-2 infection of the enterocytes (that express high levels of the ACE-2 and TMPRSS-2 receptor) produce direct epithelial destructions also leading to translocation of the intestinal microbiota to the lamina propria and then systemically. Mucosal damage is both a major determinant of long COVID, as well as of an incomplete immune recovery even in HIV-infected individuals receiving suppressive antiretroviral therapy. Was created with BioRender.com.