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Gastroenterology ; 160(3): 925-928.e4, 2021 02.
Article in English | MEDLINE | ID: covidwho-1575253
Gastroenterology ; 160(3): 809-822.e7, 2021 02.
Article in English | MEDLINE | ID: covidwho-990009


BACKGROUND AND AIMS: The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohn's disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) controls. METHODS: Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n = 495; n = 387 UC; n = 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti-tumor necrosis factor and anti-interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted. RESULTS: ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti-tumor necrosis factor rescue therapy. SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders. CONCLUSIONS: Reduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.

Angiotensin-Converting Enzyme 2/metabolism , Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Intestines/drug effects , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adolescent , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/genetics , Anti-Inflammatory Agents/adverse effects , COVID-19/enzymology , COVID-19/immunology , COVID-19/virology , Case-Control Studies , Child , Child, Preschool , Colitis, Ulcerative/enzymology , Colitis, Ulcerative/genetics , Colitis, Ulcerative/immunology , Crohn Disease/enzymology , Crohn Disease/genetics , Crohn Disease/immunology , Databases, Genetic , Female , Gene Expression Regulation, Enzymologic , Host-Pathogen Interactions , Humans , Intestines/enzymology , Intestines/immunology , Male , Middle Aged , North America , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Virus/metabolism , SARS-CoV-2/enzymology , SARS-CoV-2/immunology , Severity of Illness Index , Treatment Outcome , Tumor Necrosis Factor Inhibitors/adverse effects , Tumor Necrosis Factor-alpha/metabolism , Young Adult
Gastroenterology ; 160(3): 925-928.e4, 2021 02.
Article in English | MEDLINE | ID: covidwho-977281