The natural history of COVID-19 in vaccinated inflammatory bowel disease patients.

AIM: Assess the characteristics of break through COVID-19 in Inflammatory Bowel Disease (IBD) patients, despite complete vaccination. METHODS: Patients who reported a COVID-19 at least 3 weeks after complete vaccination were asked to answer an on-line anonymous questionnaire which included patient and disease characteristics, vaccination history, and the evolution of COVID-19. RESULTS: Among 3240 IBD patients who reported complete vaccination between 1st May 2021 and 30thJune 2022, 402 (12.4%) were infected by SARS Cov-2 [223 male, 216 Crohn's disease (CD), 186 Ulcerative Colitis (UC), mean (SD) age 42.3 (14.9) years, mean (SD) IBD duration 10.1 (9.7) years]. Three hundred and sixty-nine patients (91.8%) were infected once and 33 (8.2%) twice. The mean (SD) time between last vaccination and infection was 4.1 (1.6) months. Overall, 351 (87.3%) patients reported mild constitutional and/or respiratory symptoms, 34 (8.4%) were asymptomatic and only 17 patients (4.2%) required hospitalization. Of hospitalized patients, 2 UC patients died of COVID-19 pneumonia. The remaining hospitalized patients did not need high flow oxygen supply or ICU admission. CONCLUSIONS: A minority of completely vaccinated IBD patients developed COVID-19 which evolved with mild symptoms and a favorable outcome. These results reinforce the importance of vaccination especially in vulnerable populations.

The Natural History of Covid-19 in Vaccinated Inflammatory Bowel Disease Patients

Introduction: Patients with Inflammatory Bowel Disease (IBD), especially those on immunosuppressives (IMS), should be vaccinated against SARSCoV- 2 to prevent hospitalization, mechanical ventilation, and death. However, IMS may adversely affect response to vaccination, raising concerns as to how vulnerable these patients are to break through COVID-19 infections. Thus, we aimed to assess the proportion of IBD patients who despite complete vaccination developed COVID-19, as well as the course of COVID-19 disease. Aims & Methods: This study was an initiative of the Hellenic IBD Study Group (EOMIFNE) and involved 12 IBD referral Centers. Patients attending these Centers who reported a COVID-19 infection at least 3 weeks after vaccination completion were asked to complete an on-line anonymous questionnaire which included patient demographics and IBD clinical and therapeutic data, a detailed vaccination history, and the course and outcome of COVID-19, especially the need for hospitalization, oxygen supply, and admission to ICU. In patients with a grave outcome information was sought by family members. Result(s): On estimate, 3240 patients reported full vaccination (vaccination scheme either with combined Vaxzevria- Comirnaty or onlyComirnaty vaccine) in the 12 centers. Between 1stMay 2021 and 20thApril 2022,351 (10.8%) fully vaccinated IBD patients reported COVID-19 infection [187 male, 212 CD, 139 UC, mean (SD) age 42.3 (14.9) years, mean (SD) IBD duration mean (SD), 10.1 (9.7) years]. Among them, 322 (91.7%) were infected once and 29 (8.3%) patients twice. Seventy-three patients were receiving 5-ASAs, 15 corticosteroids, 46 azathioprine/methotrexate, 117 anti-TNFs as monotherapy and 21 in combination with azathioprine/methotrexate, and 2 with corticosteroids, 43 vedolizumab, 25 ustekinumab, 5 tofacitinib and 1 rizakinzumab at the time of COVID-19 diagnosis. Three patients did not receive any treatment. IBD was in remission in 279/351 patients (79.5%). Comorbidities were reported by 112 patients (thyroid disease 66;diabetes mellitus 13;hypertension 12;coronary heart disease 11;prior cancer 4;psoriasis 2;spondyoartropathy 2;dyslipidemia 1;and PSC 1 patient). The mean (SD) time between last vaccination dose and infection was 4.1 (1.6) months. Overall, 308 (87.7%) patients reported mild constitutional and respiratory symptoms, 29 (8.6%) were asymptomatic and only 14 patients (3.9%) required hospitalization. Of those hospitalized, 2 patients, both with UC, died because of COVID pneumonia (one aged 67, on infliximab, with diabetes and the second one aged 80, on 5-ASA, with a history of laryngeal cancer);however, the remaining 12 patients did not need high flow oxygen supply or ICU admission, and none reported symptoms of long COVID. IBD medications were stopped in 145 patients (41.3%) during the COVID-19 infection. Conclusion(s): A minority of fully vaccinated IBD vaccinated patients developed COVID-19 which was relatively mild and uneventful. These results reinforce the importance of vaccination especially in vulnerable populations.

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)

Pattern and risk factors of liver injury among hospitalized COVID-19 patients: the experience of a Greek referral hospital

Background: Although the new coronavirus (SARS-COV-2) affects predominantly the respiratory system, concomitant liver manifestations are common among COVID-19 patients. Aim: To investigate the prevalence and pattern of liver impairment (hepatocellular, cholestatic, mixed) and identify risk factors potentially associated with the liver injury in hospitalized patients with Covid-19. Materials and Methods: This retrospective study enrolled consecutive patients with Covid-19 who had evidence of liver injury on admission and/or during hospitalization in a tertiary hospital. Patient demographic, clinical and laboratory data were captured from the hospital's electronic data monitoring system. Univariate and multivariate logistic regression analysis were applied to identify risk factors for liver injury.

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).

Efficacy of switching from infliximab to golimumab in patients with ulcerative colitis in deep remission.

BACKGROUND-AIM: Intravenously administered biologicals are associated with a huge pressure to Infusion Units and increased cost. We aimed to assess the impact of switching infliximab to golimumab in ulcerative colitis (UC) patients in deep remission. Patients and method: In a prospective, single-centre pilot study UC patients on infliximab mono-therapy for = 2 years, whowere in deep remission, consented to switch to golimumab and were followed for 1 year with clinical assessment, serum and faecal biomarkers, work productivity, satisfaction with treatment and quality of life parameters. Endoscopic remission was assessed by colonoscopy at 1 year. Patients fulfilling the same inclusion criteria, who did not consent to switch to golimumab and continued to receive infliximab mono-therapy, for the same period, served as controls. PATIENTS AND METHODS: In a prospective, single-centre pilot study UC patients on infliximab mono-therapy for ≥ 2 years, who were in deep remission, consented to switch to golimumab and were followed for 1 year with clinical assessment, serum and faecal biomarkers, work productivity, satisfaction with treatment and quality of life parameters. Endoscopic remission was assessed by colonoscopy at 1 year. Patients fulfilling the same inclusion criteria, who did not consent to switch to golimumab and continued to receive infliximab mono-therapy, for the same period, served as controls. RESULTS: Between October 2015 and October 2017, 20 patients were recruited; however one patient stopped therapy because of pregnancy. All 19 patients who were switched to golimumab were still in clinical, biomarker and endoscopic remission at 1 year and maintained excellent quality of life without any complications. In the control group, 18 of 19 patients were also in deep remission, since only one patient had a flare which was managed with IFX dose intensification. During a median 3 years extension treatment with golimumab only 2 patients experienced a flare of colitis. CONCLUSIONS: This pilot study indicates that switching from in-fliximab to golimumab in UC patients in deep remission does not compromise treatment effectiveness or the course of disease; golimumab offers a valid alternative to intravenous infliximab infusions during the COVID-19 pandemic.