COVID-19-from mucosal immunology to IBD patients

Abstract

Viral infections with SARS-CoV-2 can cause a multi-facetted disease, which is not only characterized by pneumonia and overwhelming systemic inflammatory immune responses, but which can also directly affect the digestive system and infect intestinal epithelial cells. Here, we review the current understanding of intestinal tropism of SARS-CoV-2 infection, its impact on mucosal function and immunology and summarize the effect of immune-suppression in patients with inflammatory bowel disease (IBD) on disease outcome of COVID-19 and discuss IBD-relevant implications for the clinical management of SARS-CoV-2 infected individuals.

Fig. 1

Model of intestinal SARS-CoV-2 infections. A Possible routes and sites of infection; 1 = infection of nasal epithelium; 2 = alternative oral ingestion of SARS-CoV-2 particles; 3 = gastric passage of infectious SARS-CoV-2 dependent on gastric pH (influenced by proton pump inhibitor intake); 4 = infection of enteric cells and active replication of virus; 5 = fecal shedding of virus or virus parts. B Intestinal tropism of SARS-CoV2 and subsequent changes of mucosal immune composition (I-II) = binding of SARS-CoV2 to luminal angiotensin-converting enzyme 2 (ACE2); transmembrane protease serine subtype (TMPRSS) 2- and TMPRSS4-dependent internalization of SARS-CoV-2 virus; (III) viral replication and virus dependent lysis of epithelial cells, (IV) decrease in inflammatory dendritic cells (V) infiltration with effector CD4⁺ and CD8⁺ T cells; (VI) increased abundance of IEL; (VII) decrease in IL-17 producing cells, (VIII) activation of B cells as well as formation of memory B cells through long-term persistance of SARS-CoV2 in eneterocytes and production of IgM, IgM and IgA.