#GUTBlog “Speed dating” with COVID-19 and the Gut

For our next #GUTBlog, Professor El-Omar has invited our two Gut Associate Editors, Professor Siew Ng and Professor Herbert Tilg, to provide an overview of the COVID-19 related publications accepted by Gut recently.  In June 2020, many of the latest COVID-19 papers are published in paper copy.

 Prof Siew C Ng, Chinese University of Hong Kong


   Prof Herbert Tilg, Innsbruck Medical University, Austria


“The pandemic of COVID-19 has sparked a parallel viral spread: academic papers. Knowledge that SARS-CoV-2 virus is not limited to the respiratory tract but also present in the gastrointestinal tract (GI) has led to a surge in articles, letters and correspondence stamped with COVID-19 keeping us busy at Gut! Timely, novel, translational and practice changing ones have certainly found its home with us.

In the first weeks of this pandemic the association of COVID-19 with the gastrointestinal (GI) tract was only marginally recognized. Initial rates of observed diarrhoea were low and mild to moderate liver injury was observed. Importantly, only discovering that the GI tract and parts of the liver expressed the key receptor for this virus i.e. ACE2 pushed a more prominent role for this part of the body in this infection. Increasingly, several studies especially those from Europe clearly demonstrated that diarrhoea might be much more frequent and in certain patients GI symptoms were even dominating the clinical phenotype.

Overwhelming inflammation accompanied by a cytokine storm with high levels of acute phase reactants was seen especially in severely diseased patients. This cytokine storm with massive overproduction of proinflammatory cytrokines such as TNFa, IL-1β or IL-6 results in systemic disease involving most parts of the body including the central nervous system and of course the GI tract. It might well be that observed acute liver injury in COVID-19 with primarily increased transaminases is caused by such a cytokine storm. Besides a direct interaction of the virus with the GI tract, such a cytokine storm might also target the GI tract resulting in intestinal inflammation. This fits well with our observation that diarrhoea in these patients is accompanied by an increase in faecal calprotectin proving that intestinal inflammation is part of this syndrome. When such a cytokine storm is part of the syndrome, clinicians all over the world are asking whether targeting such mediators could be part of the clinical approach and indeed studies targeting IL-6 and TNFa are ongoing.

That asymptomatic children and adults may be shedding infectious virus and thecontinuous presence of the RNA in stool for several weeks after recovery have also set alarm bells ringing. Although fecal-oral transmission has not been proven, colonoscopy is considered a high risk procedure and extra caution with patient and personnel protection is paramount as highlighted by the Asian Pacific Society of Digestive Endoscopy (APSDE) guidance on practice of endoscopy during COVID-19. It is also clear that as testing becomes more widely available and pre-test probability improves, we should consider screening for COVID-19 in patients before endoscopy or surgery. Inflammatory bowel disease is yet another hot topic. Limited data to date from China, Hong Kong and Italy do not suggest an increased risk of COVID-19 in patients with IBD although the SECURE-IBD registry which has captured over 500 IBD COVID-19 positive cases globally can help delineate further insights into disease susceptibility over time. Systemic corticosteroids appeared to be associated with adverse COVID-19 outcomes among IBD patients. Corticosteroids suppress lung inflammation but may also inhibit antiviral immune responses and pathogen clearance, hence its use in COVID-19 is only recommended for hyerpinflammation states or in clinical trial settings. Recent case series from Italy has shown that in IBD, active disease, old age and co-morbidities are associated with COVID-19 complications, reassuringly TNF antagonists, commonly used in many auto-inflammatory diseases do not appear to be associated with severe COVID-19.  Currently, there is no evidence to suggest that patients with IBD in remission should cease IBD-specific medications. The largest risks during the pandemic relate not only to the virus itself, but also the emergency reorganisation of hospital, endoscopy units and general practice services to deal with the pandemic. The British Society of Gastroenterology (BSG) COVID-19 IBD Working Group have generated risk stratification to provide advice on the level of social distancing necessary for patients. The goal is to prevent acute IBD flare which may avoid fatal COVID-19 in IBD. Identifying the impact of immunomodulators or biologics on duration and effect of seropositivity against SARS-CoV-2 as well as the timing of reintroducing IBD therapies in infected individuals will be important. Inevitably, we will be living with the direct, and indirect effects of SARS-Cov-2 for some time, global collaborative efforts, public health measures and telemedicine may be the new norm and our science should evolve alongside this highly dynamic situation.”

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