We encourage you to use Adobe's editing tools (please see the next page for instructions). If this is not possible, please (i) reply to this message and send a list of corrections (in an email or attachment (Word doc or a scan)) listing each change in the following manner: line number, current text, change to be made, or (ii) print out the proof, mark your corrections clearly in black ink, and fax it to 144(0)1865355717. Please do not send corrections as track changed Word documents.Changes should be corrections of typographical errors only. Changes that contradict journal style will not be made.These proofs are for checking purposes only. They should not be considered as final publication format. The proof must not be used for any other purpose. In particular we request that you: do not post them on your personal/institutional web site, and do not print and distribute multiple copies (please use the attached offprint order form). Neither excerpts nor the article in its entirety should be included in other publications written or edited by yourself until the final version has been published and the full citation details are available. You will be sent these when the article is published.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID−) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

ObjectivesThe long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut–brain interaction after hospitalisation for SARS-CoV-2 infection.DesignGI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires.ResultsThe study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls.ConclusionCompared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls.Trial registration numberNCT04691895.

Background Endoscopic-post-operative-recurrence (ePOR) in Crohn’s disease (CD) after ileocecal resection (ICR) is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-TNF therapy to vedolizumab (VDZ) and ustekinumab (UST) in a real-world setting. Methods A retrospective multicenter study of CD-adults after curative ICR on early prophylaxis. ePOR was defined as a Rutgeerts score [RS]≥i2 or colonic-segmental-SES-CD≥6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting (IPTW) was applied to compare the effectiveness between agents. Results Included 297 patients (53.9% males, age at diagnosis 24y[19-32], age at ICR-34y[26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6%≥2 biologics, and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1-year were: 41.8%. ePOR rates by treatment groups: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1-year: past-infliximab (adj.OR=1.73[95%CI:1.01-2.97]), past-adalimumab (adj.OR=2.32[95% CI:1.35-4.01) and surgical aspects. After IPTW, the risk of ePOR within 1-year of VDZ vs. anti-TNF or UST vs. anti-TNF was comparable (OR=0.55[95%CI:0.25-1.19], OR=1.86[95%CI:0.79-4.38]), respectively. Conclusion Prevention of ePOR within 1-year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.

Background Tofacitinib is a selective immunosuppressant, the first representative of the Janus kinase family inhibitors, which has a high selectivity against other kinases of the human genome. According to the results of the study, tofacitinib inhibits JAK-1, JAK-2 and in high concentrations-JAK-3 and tyrosine kinase-2. The drug is registered in Russia for the treatment of patients with ulcerative colitis. According to the instructions for medical use, in patients with incomplete response to the induction course, it is possible to conduct an additional 8 weeks of therapy at an induction dose of 10 mg 2 times a day. The objective of the study was to identify the frequency and reasons for the need to prolong the induction course of tofacitinib in patients with ulcerative colitis. Methods 35 patients with ulcerative colitis (UC) who received tofacitinib were observed in the Department of inflammatory bowel diseases. Patients were divided into two groups. Group 1 (n = 10) of patients were bionaive. The second group of patients (n = 25) had previous experience of treatment with one or more anti-TNF-α drugs. The necessity of prolongation up to 16 weeks of induction course of tofacitinib was assessed in patients with an insufficient clinical response at week 8 of therapy (reduction of partial index of Mayo less than 30%) and lack of normalisation of laboratory parameters (CRP, haemoglobin, FCP). The comparative analysis was carried out by the method of four-field tables using nonparametric statistical criteria. Results In the follow-up period among group 1 UC patients (n = 10) who had not previously received anti-TNF-α drugs, the need for a prolonged induction course of tofacitinib was not required in any patient (0%). In the second group of patients (n = 25), previously treated with anti-TNF-α drugs, a prolonged induction course of tofacitinib was required in 9 (36%) patients (x2-4.484; p = 0.028). Conclusion The need for prolongation up to 16 weeks of the induction course of tofacitinib in patients with ulcerative colitis b is significantly higher in patients who have previously received one or more anti-TNF-α drugs.