Background and aims The COVID-19 risk and disease course in inflammatory bowel disease (IBD) patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease course and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population. Methods We conducted a multicenter, nationwide IBD cohort study in the Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population. Results We established an IBD cohort of 34,763 patients. COVID-19 was diagnosed in 100/34,763 patients (0.29%). 20/100 patients (20%) had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalization occurred in 59/100 (59.0%) patients and 13/100 (13.0%) died. All patients who deceased had comorbidities and all but one were > 65 years. In line, we identified > 1 comorbidity as an independent risk factor for hospitalization (OR 4.20, 95% CI 1.58-11.17, p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 (95% CI 236.6-349.7) versus 333.0 (95% CI 329.3-336.7) per 100,000 patients, respectively; p = 0.15). Conclusions Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% was hospitalized and 13% died. A comparable COVID-19 risk was found between the IBD cohort (100/34,763 = 0.29%) and the general Dutch population. The presence of > 1 comorbidities was an independent risk factor for hospitalization due to COVID-19.

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Background and aims A fraction of gastrointestinal stromal tumors (GIST) overexpress PDGFRA rather than KIT. Presently it is unknown if this reflects a complementary oncogenic potential of PDGFRA and KIT pathways, or heterogeneity in the cellular origin of GIST. Similarly unknown is the significance of activated Hedgehog (HH)/PATCHED1 (PTCH) signaling found in many GIST. Methods Mouse Ptch was conditionally inactivated using a Cre recombinase driven by the lysozyme M (LysM) promoter. Lineage tracing was done using R26R-LacZ reporter mice. Tumors were characterized by in situ hybridization, immunohistochemistry, Western blot and qRT-PCR. Cellular transformation was assessed by clonogenic assay. Results Inactivation of Ptch in LysM-expressing cells resulted in imatinib-responsive tumors of GIST-like localization and histology. In addition to activation of Hh signaling, the tumors showed overexpression and activation of Pdgfrα, but not of Kit. Lineage tracing revealed that LysM-expressing intestinal cells were Kit-negative. These cells were juxtapposed with Kit-positive interstitial cells of Cajal (ICC) and sometimes co-expressed Pdgfrα. In contrast to KIT, PDGFRA cooperated with HH signaling in cellular transformation. Conclusions Mutations in Ptch result in formation of Pdgfrα-positive Kit-negative GIST-like tumors in mice. These tumors may develop due to cooperativity between Hh and Pdgfrα pathways from Kit-negative cells in the intestine.