I've looked at gut from both sides now: Gastrointestinal tract involvement in the pathogenesis of SARS-CoV-2 and HIV/SIV infections

Abstract

The lumen of the gastrointestinal (GI) tract contains an incredibly diverse and extensive collection of microorganisms that can directly stimulate the immune system. There are significant data to demonstrate that the spatial localization of the microbiome can impact viral disease pathogenesis. Here we discuss recent studies that have investigated causes and consequences of GI tract pathologies in HIV, SIV, and SARS-CoV-2 infections with HIV and SIV initiating GI pathology from the basal side and SARS-CoV-2 from the luminal side. Both these infections result in alterations of the intestinal barrier, leading to microbial translocation, persistent inflammation, and T-cell immune activation. GI tract damage is one of the major contributors to multisystem inflammatory syndrome in SARS-CoV-2-infected individuals and to the incomplete immune restoration in HIV-infected subjects, even in those with robust viral control with antiretroviral therapy. While the causes of GI tract pathologies differ between these virus families, therapeutic interventions to reduce microbial translocation-induced inflammation and improve the integrity of the GI tract may improve the prognoses of infected individuals.

Keywords: AIDS - acquired immunodeficiency syndrome; COVID - 19; HIV - human immunodeficiency virus; SARS-CoV-2; SIV; barrier integrity; inflammation; microbial translocation.

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.