TNFα-Antagonist Use and Mucosal Inflammation Are Associated with Increased Intestinal Expression of SARS-CoV-2 Host Protease TMPRSS2 in Patients with Inflammatory Bowel Disease

Bangma, Amber; Voskuil, Michiel; Weersma, Rinse K.

doi:10.1053/j.gastro.2020.05.091

Cited by 11 publications

(12 citation statements)

References 5 publications

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“… 14 Concomitant upregulation of ACE2 and TMPRSS2 in the inflamed intestinal mucosa could facilitate viral entry and provide an explanation to the findings of a study that demonstrated that active disease was associated with a worse outcome of COVID-19. 2 , 5 In contrast, a recent report demonstrated that reduced ileal ACE2 expression was associated with inflammation and worse outcome of COVID-19 in patients with CD. 15 These findings underline the paradoxical role of ACE2 as it may or may not implicate activation of downstream anti-inflammatory and anti-fibrotic effects, acting as protective mechanism in active IBD.…”

Section: Discussionmentioning

confidence: 98%

“… 4 Recently, we showed that patients using TNF-α-antagonists and those with active mucosal inflammation show increased intestinal expression of the SARS-CoV-2 host protease transmembrane protease, serine 2 (TMPRSS2), indicating a potential higher susceptibility of SARS-CoV-2 infection in these patients. 5 Nonetheless, due to the lack of original research data, there is still much uncertainty about the implications of COVID-19 for patients with UC, especially for those with active disease. 6 Most importantly, guidelines covering this subgroup of patients are inconclusive at this moment, necessitating consensus-based recommendations in the absence of more evidence-based data.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of severe acute ulcerative colitis in SARS-CoV-2 infected patients: report of three cases and discussion of treatment options

Bourgonje

Linschoten

West

et al. 2021

Therap Adv Gastroenterol

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In the wake of the coronavirus disease 2019 (COVID-19) pandemic, it is unclear how asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients who present with acute severe ulcerative colitis (UC) can be treated effectively and safely. Standard treatment regimens consist of steroids, immunomodulatory drugs, and biological therapies, but therapeutic decision-making becomes challenging as there are uncertainties about how to deal with these drugs in patients with COVID-19 and active UC. Importantly, guidelines for this particular group of patients with UC are still lacking. To inform therapeutic decision-making, we describe three consecutive cases of patients with active UC and COVID-19 and discuss their treatments based on theoretical knowledge, currently available evidence and clinical observations. Three patients were identified through our national inflammatory bowel disease network [Initiative on Crohn’s and Colitis (ICC)] for whom diagnosis of SARS-CoV-2-infection was established by reverse transcription–polymerase chain reaction (RT-PCR) testing in nasopharynx, stools, and/or biopsies. Acute severe UC was diagnosed by clinical parameters, endoscopy, and histopathology. Clinical guidelines for SARS-CoV-2-negative patients advocate the use of steroids, calcineurin inhibitors, or tumor necrosis factor alpha (TNF-α)-antagonists as induction therapy, and experiences from the current three cases show that steroids and TNF-α-antagonists could also be used in patients with COVID-19. This could potentially be followed by TNF-α-antagonists, vedolizumab, or ustekinumab as maintenance therapy in these patients. Future research is warranted to investigate if, and which, immunomodulatory drugs should be used for COVID-19 patients that present with active UC. To answer this question, it is of utmost importance that future cases of patients with UC and COVID-19 are documented carefully in international registries, such as the SECURE-IBD registry.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Treatment of severe acute ulcerative colitis in SARS-CoV-2 infected patients: report of three cases and discussion of treatment options

Bourgonje

Linschoten

West

et al. 2021

Therap Adv Gastroenterol

Self Cite

View full text Add to dashboard Cite

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“…Further investigations confirmed the impact of many factors on its expression level, such as age, inflammatory state, different parts of the intestine, and cell type. This is coinciding with the altered disease manifestations in different subject groups ( Bangma et al, 2020 ), and the lack of the ACE2 expression in the upper GI tract may account for reasons why GI symptoms are not as typical as those in the respiratory system, although the epithelium in the upper GI tract also provides crucial defense against virus infection.…”

Section: Introductionmentioning

confidence: 93%

ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology

Guo

Wang

Han

et al. 2021

Front. Mol. Biosci.

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The 2019-nCoV is a rapidly contagious pneumonia caused by the recently discovered coronavirus. Although generally the most noticeable symptoms are concentrated in the lungs, the disorders in the gastrointestinal tract are of great importance in the diagnosis of 2019-nCoV. The angiotensin-converting enzyme 2 (ACE2), an important regulator of many physiological functions, including blood pressure and nutrients absorption, is recently identified as a vital entry for 2019-nCoV to enter host cells. In this review, we summarize its functions both physiologically and pathologically. We also elaborate its conflicting roles from the clews of contemporary researches, which may provide significant indications for pharmacological investigations and clinical uses.

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“…Mechanistic studies to assess risk factors for SARS-CoV-2 infection within the IBD population have focussed on the regulation of the expression of the key molecules involved in viral recognition and epithelial cell entry, ACE 2 and TMPRSS2 in the ileum and colon, and whether drugs used for IBD might alter this expression and increase vulnerability to local or systemic disease. Gene and protein expression data suggest that age, disease activity and disease location are key determinants, with confirmatory data demonstrating increased ACE 2 expression in active colonic disease and increased TMPRSS2 in ileal inflammation [15, 27]. These data require functional exploration, as do the effects of specific drugs implicated in clinical data sets as potentially determining severity or susceptibility.…”

Section: Ibd and The First Wave Of The Sars-cov-2 Pandemicmentioning

confidence: 99%

COVID-19 and Gastrointestinal Disease: Implications for the Gastroenterologist

Hunt

East

Lanas

et al. 2020

Dig Dis

109

107

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COVID-19 was initially considered to be a respiratory disease but soon after the pandemic established it became clear that the SARS-CoV-2 virus which caused the disease could lead to serious systemic consequences affecting most of the major organs including the digestive tract, liver and pancreas. This review brings together the new information which is clinically relevant to the gastroenterologist including the origins of the disease, mechanisms of tissue damage and how this affects specific patient groups, including those with inflammatory bowel disease, comorbidities and the role of immunosuppression, chronic liver disease and the risk of decompensation for those with cirrhosis. The impact of COVID-19 for gastrointestinal emergencies is addressed together with the implications for the conduct of endoscopic and other interventional and diagnostic procedures. The importance of fully understanding the pharmacology and therapeutic implications of drugs commonly used by the gastroenterologist and their relationship with COVID-19 are also highlighted. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who are often requiring mechanical ventilation and life-support. Some re-purposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19 GI symptoms and also can induce iatrogenic liver injury. Ongoing clinical studies will hopefully identify effective drugs with a risk-benefit ratio which will be more favorable than many recently tried treatments.

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TNFα-Antagonist Use and Mucosal Inflammation Are Associated with Increased Intestinal Expression of SARS-CoV-2 Host Protease TMPRSS2 in Patients with Inflammatory Bowel Disease

Cited by 11 publications

References 5 publications

Treatment of severe acute ulcerative colitis in SARS-CoV-2 infected patients: report of three cases and discussion of treatment options

Treatment of severe acute ulcerative colitis in SARS-CoV-2 infected patients: report of three cases and discussion of treatment options

ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology

COVID-19 and Gastrointestinal Disease: Implications for the Gastroenterologist

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