Therapies for the treatment of inflammatory bowel disease (IBD) may have a potential use in patients with coronavirus disease 2019 (COVID-19). These findings, from multiple large cohort studies, were published in Gastroenterology.
Researchers from the Icahn School of Medicine at Mount Sinai in New York City combined data from large cross sectional and longitudinal cohorts, which included blood and biopsy samples and RNA-sequencing expression profiles from both patients with IBD and healthy controls for this analysis. Gene regulatory networks were generated and IBD drug response was investigated and compared with COVID-19 response signatures.
Corticosteroid use among patients with Crohn disease was found to significantly decrease angiotensin converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) mRNA expression in rectal tissue (P =.04 and P =8e-7, respectively). Thiopurine decreased ACE2 expression in rectal tissue from patients with Crohn disease (P =.017), while 5-Aminosalicylate decreased TMPRSS2 expression in colon tissue from patients with ulcerative colitis (P =.045). Biologics that targeted tumor necrosis factor (TNF; adalimumab or infliximab) increased both ACE2 mRNA (P =.002) and TMPRSS2 mRNA in rectal tissue from patients with Crohn disease (P =.002 and P <.001, respectively) and in ulcerative colitis (P =.036).
A regulatory subnetwork analysis of ACE2 revealed associations with solute carrier (SLC) transport, xenobiotics, metabolism of vitamins, and hexose transport. TMPRSS2 subnetwork analysis indicated that cell-cell communication, tight junction interaction, O-linked glycosylation of mucins, and membrane trafficking were significantly associated.
Expression patterns from patients with IBD or COVID-19 indicated the presence of overlapping molecular pathways between the 2 diseases. Genes that were up-regulated in patients with COVID-19 were similarly up-regulated in patients with IBD, but not in healthy controls. The COVID-19 gene network shared expression patterns for 148 genes with samples from the ileum of patients with Crohn disease, 213 genes with samples from the colon of patients with ulcerative colitis, and 170 from the colon of patients with Crohn disease.
These significant subnetworks were compared with the alterations to expression after IBD treatment. The response to treatment by ustekinumab or infliximab at 4 weeks had significant overlap with the genes that were up-regulated among patients with COVID-19.
This study was limited by the combination of cross-sectional cohort studies that sourced data from varying tissues from patients with differing diseases, which may have introduced some bias.
The study authors concluded that significant overlap between networks of genes that had altered expression after COVID-19 infection and active IBD indicated that the therapies commonly given to patients with IBD may have some therapeutic benefit for the treatment of COVID-19. These results warrant further study.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Suárez-Fariñas M, Tokuyama M, Wei G, et al. Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease. Published online September 24, 2020. Gastroenterology. doi: 10.1053/j.gastro.2020.09.029