Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2-related Disease

肠道炎症调节 ACE2 和 TMPRSS2 的表达,并可能与 SARS-CoV-2 相关疾病的发病机制重叠

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作者:Mayte Suárez-Fariñas, Minami Tokuyama, Gabrielle Wei, Ruiqi Huang, Alexandra Livanos, Divya Jha, Anais Levescot, Haritz Irizar, Roman Kosoy, Sascha Cording, Wenhui Wang, Bojan Losic, Ryan C Ungaro, Antonio Di'Narzo, Gustavo Martinez-Delgado, Maria Suprun, Michael J Corley, Aleksandar Stojmirovic, Sa

Aims

The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes.

Background and aims

The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes.

Conclusions

These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. Preprint doi: https://doi.org/10.1101/2020.05.21.109124.

Methods

Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation, and IBD treatment.

Results

A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. Commonly used IBD medications, both biologic and nonbiologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. In addition, we have defined molecular responses to COVID-19 infection that are also enriched in IBD, pointing to shared molecular networks between COVID-19 and IBD. Conclusions: These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. Preprint doi: https://doi.org/10.1101/2020.05.21.109124.

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