PATIENTS WITH INFLAMMATORY BOWEL DISEASES HAVE IMPAIRED ANTIBODY PRODUCTION AFTER ANTI-SARS-COV-2 VACCINATION, ESPECIALLY THOSE ON ANTI-TNFα OR COMBINATION TREATMENT OF BIOLOGICS PLUS IMMUNOMODULATORS: RESULTS FROM A PANHELLENIC REGISTRY

Background: Patients with inflammatory bowel diseases (IBD) are commonly treated with immunosuppressive agents. Following the novel corona virus (SARS-CoV-2) pandemic, these patients received early the currently EMA approved vaccines. Data on efficacy and safety of SARS-CoV-2 vaccination on this population are lacking. Methods: Greek IBD patients, from 10 tertiary referral centres, who had completed the initial vaccination protocol with the available anti-COVID-19 vaccines (BNT162b2, mRNA-1273, Ad26.CoV2.S, ChAdOx1) at least two weeks before enrolment, were prospectively studied. Demographic and safety data were collected and blood samples were drawn for serum Anti-S1 IgG measurement [Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (IgG)]. Results: In total 403 IBD patients (59% Crohn's disease, median age 45 years, 53% male) and 124 healthy controls (HC) were included (Table 1). Antibody testing was conducted after a median of 31 (IQR, 23-46) days post-vaccination. Following a full vaccination regimen, 98% of IBD patients seroconverted (anti-S1 IgG³11 RU/ml). In total, IBD patients had lower anti-S1 levels than HC (RU/ ml 108 vs 133 RU/ml, P=0.00009) Administration of mRNA vaccines resulted in higher seroconversion rates and higher antibody titers than viral vector ones (98.6% vs 93.6%, P= 0.02 and 111.2 RU/ml vs 76 RU/ml, P<0.0001, respectively). Treatment with vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or ustekinumab monotherapy (P=0.02 and P=0.03). Longer timing between vaccination and antibody measurement was independently associated with impaired vaccine response. In multivariable analysis, specifically in mRNA-vaccinated cohort, older age, anti-TNFα treatment and treatment with biologics plus IMMs were significantly associated with lower antibody response (P=0.01, P=0.008, and P=0.02 respectively). Patients with prior COVID-19 infection showed numerically higher levels of antibodies. All vaccines were safe in IBD patients. Conclusions: Patients with IBD have high seroconversion rates to anti-SARS-CoV-2 vaccines. However, they demonstrate impaired antibody responses compared to HC. Patients receiving viral vector vaccines, and those on anti-TNFα or combination treatment may have further response impairment and it is important to consider booster vaccination in those low-response groups. (Table Presented)

REAL WORLD USE AND ADVERSE EVENTS OF SARS-COV-2 VACCINATION IN GREEK PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Introduction Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions for and unfavorable effects of COVID-19 vaccination in this group. The aim of this study was to investigate the real world use and adverse events (AE) of vaccines against COVID-19 in IBD patients. Aims and Methods Fully vaccinated IBD patients followed in Greek centers were invited to participate in an anonymous online self reporting survey that included information regarding their demographics, clinical characteristics, treatment, vaccination perceptions and potential AE. Patients were vaccinated with either messenger-RNA or viral vector vaccines that are currently EMA approved. AE were stated as any kind of new symptom or sign onset, including localized (at the injection site) or systematic ones (fatigue, headache, allergic reactions, fever, lymphadenopathy, myalgias/arthralgias and gastrointestinal disorders). Results A total of 1007 IBD patients [male 50.5%, median age (IQR) 44 (35-55) years, Crohn's disease 64.3%, history of COVID-19 infection 2.6%] who completed the survey after they have fulfilled their vaccination program were included. Detailed demographics and clinical characteristics of the study population are presented in Table 1. More than half of the patients (51%) stated that they show confidence in vaccination whereas the rest although hesitant admitted the protection it offers. The median (IQR) time between 2nd vaccine dose and questionnaire completion was 15 (5-43) days. There were no serious AE leading to emergency room visit or hospitalization. Total AE were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), reduced to 44% and 51% when excluding isolated injection site reactions respectively. Systemic AEs were more common after D2 (P<0.0001). Very few patients reported new onset abdominal symptoms [abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)]. In the multiple regression analysis AE occurrence was positively associated with young age, female gender and blood type AB rhesus positiveafter both doses, whereas inactive disease was negatively associated with AE only in D1 (p= 0.044) No association with the use of medications including advanced therapy was found (p>0.05), except from corticosteroids after D2 (p=0.003) but it was a small (32/1007 patients) heterogenous (monotherapy, double or triple immunosupression) sample to draw conclusions (Table 2). Conclusions The presence of SARs-CoV-2 vaccination AE in Greek patients with IBD is similar to the reported in other populations. Young age and female gender but not IBD related medications are associated with the development of AEs after both doses. (Table Presented) (Table Presented)

IMPLEMENTATION AND SHORT-TERM ADVERSE EVENTS OF ANTI-SARSCOV-2 VACCINES IN INFLAMMATORY BOWEL DISEASE PATIENTS: AN INTERNATIONAL WEB-BASED SURVEY

Introduction: Pivotal anti-SARS-CoV-2 vaccines clinical trials did not include patients with immune-mediated conditions such as inflammatory bowel disease (IBD). We aimed to describe the implementation of anti-SARS-CoV-2 vaccines among IBD patients, patients' concerns before vaccination and side-effect profile of the anti-SARS-CoV-2 vaccines using real-world data. Methods: An anonymous web-based self-completed survey was distributed in 36 European countries between June and July 2021. The results of patients' characteristics, concerns, vaccination status and side-effect profile were analysed using descriptive statistics and logistic regression. Results: Among the 3272 IBD patients completing the survey (0.1% of the IBD European population), 79.6% had received at least one dose of anti-SARS-CoV- 2 vaccine, and 71.7% had completed the vaccination process. Most of the patients (70.6%) were vaccinated with the Pfizer-BioNTech (BNT162b2) vaccine. Patients over 60 years old had a significantly higher rate of vaccination (OR 2.98, 95% CI 2.20-4.03, p<0.001). Patients' main concerns before vaccination were the possibility of having worse vaccine-related adverse events due to their IBD (24.6%), having an IBD flare after vaccination (21.1%) and reduced vaccine efficacy due to IBD or associated immunosuppression (17.6%). After the first dose of the vaccine, 72.4% had local symptoms at the injection site and 51.4% had systemic symptoms (5 patients had non-specified thrombosis). Adverse events were less frequent after the second dose of the vaccine and in older patients. When comparing with previous studies from the general population, the IBD patients answering the survey did not seem to have increased side effects (table 1). Only a minority of the patients were hospitalized (0.3%), needed a consultation (3.6%) or had to change IBD therapy (13.4%) after anti- SARS-CoV-2 vaccination. Conclusion: Although IBD patients raised concerns about the safety and efficacy of anti-SARS-CoV-2 vaccines, the implementation of vaccination in those responding to our survey was high and the adverse events were comparable to the general population, with minimal impact on their IBD. (Table Presented)

Patients with Inflammatory Bowel Diseases on anti-TNF treatment have impaired antibody production after Anti-SARS-CoV-2 vaccination: Results from a Panhellenic registry

Background: The novel corona virus (SARS-CoV-2) outbreak was declared as a pandemic in March 2020;this prompted the need for rapid vaccine development. Currently four EMA approved vaccines exist but their efficacy and safety data on patients with Inflammatory Bowel diseases are limited. Methods: Greek IBD patients, from 10 tertiary referral centres, who had completed the initial vaccination protocol with the available anti-COVID-19 vaccines at least two weeks before enrolment, were prospectively studied. Demographic and safety data were collected and blood samples were drawn for serum Anti-S1 IgG measurement [Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (IgG)]. Results: In total 403 IBD patients (59% Crohn's disease, median age 45 years, 53% male) and 124 healthy controls (HC) were included (Table 1). Antibody testing was conducted after a median of 31 (IQR, 23-46) days post-vaccination. Following a full vaccination regimen, 98% of IBD patients seroconverted (anti-S1 IgG≥11 RU/ ml). Administration of mRNA vaccines resulted in higher seroconversion rates and higher antibody titers than viral vector ones (98.6% vs 93.6%, P=0.02 and 111.2 RU/ml vs 76 RU/ml, P<0.0001, respectively). In total, IBD patients had lower anti-S1 levels than HC (RU/ ml 108 vs 133 RU/ml, P=0.00009). IBD patients without immunosuppression had higher antibody titers than immunocompromised patients (P=0.012). In univariable analysis, older age, longer time since vaccination, and treatment with corticosteroids, immunomodulators, anti-TNFα or combination therapy were associated with lower anti- S1 titers. In contrast, higher anti-S1 levels were detected in patients on vedolizumab monotherapy or non-immunosuppressive treatment. In multivariable analysis, only age, time since vaccination, and anti- TNFα therapy remained significant (P=0.011, P=0.002, and P=0.013 respectively). Treatment with vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or ustekinumab monotherapy (P=0.023 and P=0.032). Patients with prior COVID-19 infection showed numerically higher levels of Abs. All vaccines were safe in IBD patients. Conclusion: Patients with IBD have high seroconversion rates to anti- SARS-CoV-2 vaccines, with mRNA vaccines being more efficacious. However, IBD patients have impaired response to vaccination comparing to HC. Lower antibody responses were observed in patients who received viral vector vaccines, in older patients, and in those on anti- TNFα treatment. It is important to consider booster vaccination in those low-response groups.

Real world use and adverse events of SARs-CoV-2 vaccination in Greek patients with Inflammatory Bowel Disease

Background: Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions for and unfavorable effects of COVID-19 vaccination in this group. The aim of this study was to investigate the real world use and adverse events (AE) of vaccines against COVID-19 in IBD patients. Methods: Fully vaccinated IBD patients followed in Greek centers were invited to participate in an anonymous online self reporting survey that included information regarding their demographics, clinical characteristics, treatment, vaccination perceptions and potential AEs. Patients were vaccinated with either messenger-RNA or viral vector vaccines that are currently EMA approved. AEs were stated as any kind of new symptom or sign onset, including localized (at the injection site) or systematic ones (fatigue, headache, allergic reactions, fever, lymphadenopathy, myalgias/arthralgias and gastrointestinal disorders). Results: A total of 1007 IBD patients [male 50.5%, median age (IQR) 44 (35-55) years, Crohn's disease 64.3%, history of COVID- 19 infection 2.6%] who completed the survey after they have fulfilled their vaccination program were included. Detailed demographics and clinical characteristics of the study population are presented in Table 1. More than half of the patients (51%) stated that they show confidence in vaccination whereas the rest although reluctant/hesitant admitted the protection it offers. The median (IQR) time between 2nd vaccine dose and questionnaire completion was 15 (5-43) days. There were no serious AEs leading to emergency room visit or hospitalization. Total AEs were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), reduced to 44% and 51% when excluding isolated injection site reactions respectively. Systemic AEs were more common after D2 (P<0.0001). Very few patients reported new onset abdominal symptoms [abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)]. In the multiple regression analysis AE occurrence was positively associated with young age and female gender after both doses, whereas inactive disease was negatively associated with AE only in D1 (p=0.044). No association with the use of medications including advanced therapy was found (p>0.05), except from corticosteroids after D2 (p=0.003) but it was a small (32/1007 patients) heterogenous (monotherapy, double or triple immunosupression) sample to draw conclusions. Conclusion: The presence of SARs-CoV-2 vaccination AEs in Greek patients with IBD is similar to the reported in other populations. Young age and female gender but not IBD related medications are associated with the development of AEs after both doses.

Effects of COVID-19 on employment in IBD patients

Introduction: There is an ongoing concern over the impact of COVID-19 on IBD patients. A significant proportion of IBD patients are treated with immunosuppressive medications and their effects on COVID-19 susceptibility and outcomes remain of concern to patients and physicians alike. Apart from the clinical outcome, the pandemic may have other psychosocial effects on this vulnerable cohort, such as employment stability. Aims & Methods: The primary aim of this study was to analyze the percentage of patients who tested themselves for COVID-19 and the outcome of those who tested positive. A secondary aim was to assess their employment status. This was a multicentre international study whereby IBD patients (>18 years) in clinical remission over the last year, were asked to answer an anonymous questionnaire. Demographic data, type of IBD, current and previous medication, admissions to hospital, were collected. Exclusion criteria included patients with IBD flares requiring corticosteroids in the previous 12 months. Results: 585 patients (CD: n=325) from 8 European Centres and Israel participated in the study. The mean patient age was 40.1 years (SD+/- 13.1). 21.6% were smokers and 48.5% were non-smokers. The rest were ex-smokers. 44.5% (n=255 ) of patients were tested for Covid-19 and 5.1% (n=13) were positive. The majority were treated at home (92.3%) with only one patient requiring hospital admission. This was a 33-year-old female smoker with UC (E3 disease activity) on anti-TNF therapy. 66.7% of positive cases were on anti-TNF medication and 22.2% were on thiopurines. None of the positive cases were on dual antiTNF/thiopurine therapy. 7.2% of patients had family members who also tested positive for Covid-19. Almost half of all patients (45.2%) had their job affected during the pandemic and this was more prevalent in the UC cohort (P<0.05). 70% of patients switched to remote work from home and 21.4% became unemployed. The average age of patients becoming unemployed was 39.3year (SD+/- 11.9). Conclusion: Nearly half of our cohort (45.2%) were tested for Covid-19. The majority (92.3%) were treated at home, even though two thirds of them were on Anti-TNF medication. Unemployment rates affected 1 in 5 individuals and measures promoting remote work have been taken up wisely by IBD patients. Though the clinical outcomes were excellent, the psychological effects of unemployment may have yet to be considered.

The natural history of COVID-19 in patients with IBD: A nationwide study by the hellenic society for the study of IBD

Introduction: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to the frequent administration of immune-modifying treatments. Aims & Methods: We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via the unbiased reporting of all cases that were registered during the first and second waves of the pandemic. Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBDassociated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission, and death). Results: We identified 160 IBD patients who were diagnosed with COVID- 19 during the study period (male:56.9%;mean age=41.6 [SD=14.8] years;CD:64.4%). Adverse outcomes were reported in 34 patients (21.3%), including 3 ICU admissions (1.9%) and 2 deaths (1.3%). As shown in the table prognostic factor for adverse events due to COVID-19 in IBD patients were sought. Through multivariate logistic regression age (OR=1.04, 95% CI=1-1.08) and dyspnoea at presentation (OR=8.72, 95% CI=2.14-35.57) were identified as negative prognostic factors while there was also a tendency for fever at presentation (OR=3.23, 95% CI=0.91-11.43). In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable course COVID-19 (OR=0.33, 95% CI=0.13-0.84). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous medications. Conclusion: IBD patients who developed COVID-19 had a benign course with adverse outcomes being scarce. Treatment with biologics had a beneficial effect, supporting the continuation of therapy during the pandemic. (Table Presented).

COVID-19 and Gastrointestinal manifestations

SARS-CoV-2 appeared in December 2019 in the Wuhan and has been rapidly spreading from China to other countries. In March 2020 has been declared a pandemic and one of the most important public health emergencies. It's a virus that typically concern respiratory system, and is manifested by fever, dry cough, dyspnea and fatigue. Moreover, gastrointestinal, and hepatic manifestations can also appear. In this article we briefly describe the link between angiotensin-converting enzyme II (ACE2) and digestive system, a receptor that mightly can be the entry mechanism of SARS-COV2. Gastrointestinal symptoms can be abdominal pain, nausea, vomiting and diarrhea. Liver chemistry abnormalities are also common and include elevation of aspartate transferase, alanine transferase, and total bilirubin. Furthermore, an important fact is that viral RNA has been isolated from stool specimens of COVID-19 patients even more when tests from respiratory system turn negative. Finally, we underline the role of gut microbiota between SARS - COV2 infection and inflammatory respone and immune homeostasis.

ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the COVID-19 pandemic

Europe is severely affected from Covid-19 pandemic with an exponential increase in incident infections and deaths. The clinical manifestations of COVID-19 can be subtle, encompassing a broad spectrum from asymptomatic mild disease to severe respiratory illness. Health care professionals in endoscopy units are at increased risk of infection from COVID-19. Infection prevention and control has been shown to be dramatically effective in assuring the safety of both health care professionals and patients. The prolonged lockdown period across Europe resulted in the cancellation of elective GI endoscopies as only urgent endoscopies were performed. The aim of this present Position Statement is to provide up-dated evidence-based guidance on endoscopy practice for the lockdown and the post-lockdown phase of the COVID-19 pandemic.