Severe Acute Respiratory Syndrome Coronavirus 2 Attachment Receptor Angiotensin-Converting Enzyme 2 Is Decreased in Crohn’s Disease and Regulated By Microbial and Inflammatory Signaling

Abstract

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e17. Learning Objective: Upon completion of this CME, successful learners will be able explain donor screening processes for fecal microbiota transplantation and describe commonly reported adverse events.BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and longterm safety. METHODS: A prospective survey-based study was conducted (September 2012-June 2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (shortterm), and 2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey nonresponse bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey, and comorbidities. P < .05 was considered statistically significant. RESULTS: Overall, 609 patients underwent FMT; median age was 56 years (range, 18-94), 64.8% were women, 22.8% had inflammatory bowel disease (IBD). At short-term follow-up (n ¼ 609), >60% of patients had diarrhea and 19%-33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysisdependent kidney disease, and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in women and lower in IBD (all P < .05). For long-term follow-up (n ¼ 447), median time of follow-up was 3.7 years (range, 2.0-6.8). Overall, 73 new diagnoses were reported: 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0-73) post-FMT. CONCLUSION: FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.

Circulating Adaptive Immune Cells Expressing the Gut Homing Marker α4β7 Integrin Are Decreased in COVID-19

“…The lung and the gut are considered the main portals of entry for SARS-CoV-2 (37,38). However, pulmonary manifestation dominates the clinical disease phenotype and only a subset of hospitalized patients suffers from gastrointestinal symptoms (2,4).…”

COVID-19: biologic and immunosuppressive therapy in gastroenterology and hepatology

“…For instance, in one study, 36 of 395 hospitalized patients with COVID-19 had an active malignancy 25 . Interestingly, gastrointestinal symptoms might be caused by direct infection of the intestinal tract, as tongue epithelial cells, pharyngeal cells, stomach cells and epithelial cells of the small and large intestine all express ACE2 (refs 26 , 27 ). The highest expression levels of ACE2 with apical co-expression of TMPRSS2 are detected in human intestinal epithelial cells of the terminal ileum 19 , 27 (Fig.…”

“…In patients with Crohn’s disease, a high expression of ACE2 and TMPRSS2 in ileal and colonic epithelial cells is observed 26 , 27 . However, ACE2 (mRNA and protein levels) but not TMPRSS2 expression is substantially lower in inflamed ilea compared with uninflamed control patients and is negatively correlated with inflammation markers such as S100A8 (ref.…”

“…However, ACE2 (mRNA and protein levels) but not TMPRSS2 expression is substantially lower in inflamed ilea compared with uninflamed control patients and is negatively correlated with inflammation markers such as S100A8 (ref. 27 ). ACE2 is particularly reduced in patients who subsequently develop severe disease 54 .…”

SARS-CoV-2 Virus Manifestations in the Gastrointestinal Tract: Therapeutic Implications

“…Garg et al [ 23 ] showed that ACE2 activity and angiotensin appear in higher concentrations in IBD patients in comparison with healthy controls. In contrast, Patankar et al [ 24 ] found that ACE2 but not TMPRSS2 expression is lower in the inflamed ilea of CD patients than in healthy controls. They studied dif­ferent IBD mouse models and found that ACE2 but not TMPRSS2 was downregulated during inflammation.…”