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Reviews of "Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon"

Reviewers: Girija Goyal, Cicely Fadel, Donald Ingber (Wyss Institute) | ๐Ÿ“’๐Ÿ“’๐Ÿ“’โ—ป๏ธโ—ป๏ธ โ€ข Magdalena Kasendra (Cincinnati Childrenโ€™s Hospital Medical Center) | ๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“— โ—ป๏ธ

Published onAug 19, 2020
Reviews of "Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon"
key-enterThis Pub is a Review of
Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon
Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon
Description

ABSTRACT Patients with IBD are considered immunosuppressed, but do not seem more vulnerable for COVID-19. Nevertheless, intestinal inflammation has shown an important risk factor for SARS-CoV-2 infection and prognosis. Therefore, we investigated the effect of intestinal inflammation on the viral intestinal entry mechanisms, including ACE2, in IBD.We collected (un)inflamed mucosal biopsies from CD (n=193) and UC (n=158) patients, and 51 matched non-IBD controls for RNA sequencing, differential gene expression and co-expression analysis. Organoids from UC patients were subjected to an inflammatory mix and processed for RNA sequencing. Transmural ileal biopsies were processed for single-cell (sc) sequencing. Publicly available colonic sc-RNA sequencing data, and microarrays from tissue pre/post anti-TNF therapy, were analyzed.In inflamed CD ileum, ACE2 was significantly decreased compared to control ileum (p=4.6E-07), whereas colonic ACE2 expression was higher in inflamed colon of CD/UC compared to control (p=8.3E-03; p=1.9E-03). Sc-RNA sequencing confirmed this ACE2 dysregulation, and exclusive epithelial ACE2 expression. Network analyses highlighted HNF4A as key regulator of ileal ACE2, while pro-inflammatory cytokines and interferon regulating factors regulated colonic ACE2. Inflammatory stimuli upregulated ACE2 in UC organoids (p=1.7E-02), not in non-IBD controls (p=9.1E-01). Anti-TNF therapy restored colonic ACE2 dysregulation in responders.Intestinal inflammation alters SARS-CoV-2 coreceptors in the intestine, with opposing effects in ileum and colon. HNF4A, an IBD susceptibility gene, is an important upstream regulator of ACE2 in ileum, whereas interferon signaling dominates in colon. Our data support the importance of adequate control of IBD in order to reduce risk of (complicated) COVID-19.

To read the original manuscript, click the link above.

Summary of Reviews: Study claims increased susceptibility of IBD patients to SARS-CoV-2 infection. Study lacks sufficient evidence to support the authorsโ€™ claims concerning the importance of IBD medication in COVID-19 risk management. Claims are not actionable except to prompt further research.

Reviewer 1 (Girija Goyal,ย Cicely Fadel,ย Donald Ingber) | ๐Ÿ“’๐Ÿ“’๐Ÿ“’ โ—ป๏ธโ—ป๏ธ

Reviewer 2 (Magdalena Kasendra) | ๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“—โ—ป๏ธ

RR:C19 Strength of Evidence Scale Key

๐Ÿ“• โ—ป๏ธโ—ป๏ธโ—ป๏ธโ—ป๏ธ = Misleading

๐Ÿ“™๐Ÿ“™ โ—ป๏ธโ—ป๏ธโ—ป๏ธ = Not Informative

๐Ÿ“’๐Ÿ“’๐Ÿ“’ โ—ป๏ธโ—ป๏ธ = Potentially Informative

๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“—โ—ป๏ธ = Reliable

๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜ = Strong

To read the reviews, click the links below.ย 

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