K nowledge of clinically relevant targets of individual treatments is important for improving management of patients with inflammatory bowel diseases (IBD). The Selecting Therapeutic Targets in IBD (STRIDE) program was initiated by the International Organization for the Study of IBD (IOIBD) in 2013 using an evidencebased expert consensus process. It subsequently led to a *Authors share co-first authorship.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported.Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.

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Secukinumab, ixekizumab and brodalumab are monoclonal antibody therapies that inhibit interleukin (IL)-17 activity and are widely used for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis. The promising efficacy results in dermatology and rheumatology prompted the evaluation of these drugs in Crohn’s disease and ulcerative colitis, but the onset of paradoxical events (disease exacerbation after treatment with a theoretically curative drug) prevented their approval in patients with inflammatory bowel diseases (IBDs). To date, the pathophysiological mechanisms underlying these paradoxical effects are not well defined, and there are no clear guidelines for the management of patients with disease flare or new IBD onset after anti-IL-17 drug therapy. In this review, we summarise the literature on putative mechanisms, the clinical digestive effects after therapy with IL-17 inhibitors and provide guidance for the management of these paradoxical effects in clinical practice.

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Background & Aims Data on the c linical characteristics of patients with inflammatory bowel diseases (IBDs) with coronavirus disease 2019 (COVID-19) are scarce. The aim of our systematic review was to investigate symptoms and diagnostic–therapeutic management of IBD patients with COVID-19. Methods We searched PubMed, Embase, Web of Science, and MedRxiv up to July 29, 2020, to identify all studies reporting clinical information on adult and pediatric IBD patients with confirmed COVID-19. Results Twenty-three studies met our inclusion criteria, including 243,760 IBD patients. COVID-19 was diagnosed in 1028 patients (509 with Crohn’s disease [49.5%], 428 with ulcerative colitis [41.6%], 49 with indeterminate colitis [4.8%], and 42 with missing data [4.1%]), accounting for a cumulative prevalence of 0.4%. Viral infection occurred more frequently in males than in females (56.5% vs 39.7%), and the mean age ranged from 14 to 85 years. The most common symptoms were fever (48.3%), cough (46.5%), and diarrhea (20.5%), and a COVID-19 diagnosis was achieved mainly through polymerase chain reaction analysis of nasopharyngeal swabs (94.4%) and chest computed tomography scans (38.9%). Hydroxychloroquine (23.9%), lopinavir/ritonavir (8.2%), steroids (3.2%), and antibiotics (3.1%) were the most used drugs. Overall, approximately a third of patients were hospitalized (30.6%), and 11.4% of them required admission to the intensive care unit. In total, 29 COVID-19–related deaths were reported (3.8%), and increasing age and the presence of comorbidities were recognized as risk factors for COVID-19 and negative outcomes. Conclusions Diarrhea occurs more frequently in IBD patients with COVID-19 than in the non-IBD population. Further studies are needed to define the optimal diagnostic–therapeutic approach in IBD patients with COVID-19.

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