Reappraisal of COVID-19 Risk for Patients with Inflammatory Bowel Disease (IBD): Withdrawal of the British Society of Gastroenterology IBD Risk Grid

Early in the pandemic, there was significant concern about how COVID-19 may impact patients with inflammatory bowel disease (IBD). Would IBD, as a chronic immune-mediated condition, be a risk factor for more severe COVID-19? Would medications used to treat IBD, in particularly immunosuppressants, increase the likelihood of hospitalization or death due to COVID-19? However, at the start of the pandemic there was a paucity of data to guide decision making for patients with IBD. In this setting, many national and international societies issued statements on management of IBD to provide initial guidance to gastroenterologists and patients with IBD. The British Society of Gastroenterology (BSG) published an IBD risk grid for COVID-19 severity in April 2020 that proposed a framework for categorizing patients with IBD into those more likely to be vulnerable to COVID-19 primarily based on co-morbidities and disease characteristics. Patients deemed at moderate risk were advised to practice stringent social distancing while those at high risk were recommended to practice “shielding,” the strictest advice for isolating from others. The authors of the BSG IBD risk grid recently issued a statement withdrawing this guidance noting a number of factors including that the vast majority of IBD patients are not at increased risk of adverse COVID-19 outcomes, the reduced severity of disease with recent variants, and the effectiveness of COVID-19 vaccines

COVID-19 and Inflammatory Bowel Disease: Lessons Learned, Practical Recommendations, and Unanswered Questions

On March 11, 2020 the World Health Organization declared the 2019 novel coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) epidemic a global pandemic. Physicians, scientists, and patients scrambled to gain an understanding of the implications of this dire situation, and societies and organizations tried to provide guidance of best practices and precautions. In the inflammatory bowel disease community (IBD), the International Organization for the study of IBD (IOIBD) convened their expert members and performed a RAND panel assessment to develop recommendations for patients and providers. Others developed an international open registry to collect data about patients with IBD who developed Coronavirus Disease (COVID-19), the Surveillance Epidemiology of COVID-19 Under Research Exclusion (SECURE-IBD), in order to collect evidence on how COVID-19 impacted IBD patients. To date, SECURE-IBD has amassed 3,493 cases with outcomes3 and published initial analyses. In addition, there were multiple articles published with individual or multi-center experiences, city or regional experiences, and many case reports about IBD or immunemediated disease outcomes. Separately, there was significant activity by translational and basic scientists working to define and describe the pathophysiology of SARS-CoV-2 infections

The impact of vedolizumab on COVID-19 outcomes among adult IBD patients in the SECURE-IBD registry

Introduction The impact of immune-modifying therapies on outcomes of Coronavirus disease of 2019 (COVID-19) is variable. The purpose of this study was to determine the impact of vedolizumab (VDZ), a gut-selective anti-integrin, on COVID-19 outcomes in inflammatory bowel disease (IBD) patients. Methods Using data from the Surveillance of Coronavirus Under Research Exclusion for IBD (SECURE-IBD), an international registry of IBD patients with confirmed COVID-19, we studied the impact of VDZ on COVID-19 hospitalization and severe COVID-19 (intensive care unit stay, mechanical ventilation and/or death). Results Of 3,647 adult patients on any IBD medication in the registry, 457 (12.5%) patients were on VDZ. On multivariable analyses using backward selection of covariates, VDZ use was not associated with hospitalization or severe COVID-19 when comparing to patients on all other medications [adjusted odds ratio (aOR) 0.87; 95% confidence interval (CI) 0.71, 1.1 and aOR 0.95; 95% CI 0.53; 1.73, respectively]. On comparing VDZ monotherapy to anti-TNF monotherapy, the odds for hospitalization, but not severe COVID-19, were higher (aOR CI 1.39; 95% CI 1.001, 1.90 and aOR 2.92; 95% CI 0.98, 8.71, respectively). In an exploratory analysis, VDZ monotherapy, compared to anti-TNF monotherapy, was associated with new-onset GI symptoms at the time of COVID-19, especially among patients whose IBD was in remission. Conclusions COVID-19 outcomes among IBD patients on VDZ are comparable to those on all other therapies. Hospitalization, but not severe COVID-19, is more likely with VDZ monotherapy than with anti-TNF monotherapy. Overall, VDZ appears to be safe in IBD patients with COVID-19

New Gastrointestinal Symptoms Are Common in Inflammatory Bowel Disease Patients With COVID-19: Data From an International Registry

Coronavirus disease 2019 (COVID-19) can cause gastrointestinal (GI) symptoms. A prior meta-analysis suggested that up to 17.6% of COVID-19 patients have GI symptoms. Data are conflicting on the association of GI symptoms with COVID-19 outcomes, with some reports suggesting worse prognosis among those with GI symptoms while others finding improved outcomes. There are limited data on COVID-19 and GI symptoms among inflammatory bowel disease (IBD) patients. A single-center study of 80 IBD patients with COVID-19 observed that they were more likely to present with abdominal pain and diarrhea than non-IBD controls. In addition, a prior systematic review on just over 400 patients found nearly one-quarter of IBD patients with COVID-19 had diarrhea.6 Using a large, international database, we aimed to describe new onset GI symptoms and their association with clinical outcomes in patients with IBD who develop COVID-19

Presence of Comorbidities Associated with Severe Coronavirus Infection in Patients with Inflammatory Bowel Disease

Background Comorbidities increase the risk of coronavirus disease 2019 (COVID-19) hospitalization and mortality. As many comorbidities are common in patients with inflammatory bowel diseases (IBD), we sought to investigate the effects of comorbidities in these patients on infection severity. Aim To evaluate association between individual comorbidities and COVID-19 infection severity among patients with IBD. Methods Data were obtained from SECURE-IBD, an international registry created to evaluate COVID-19 outcomes in patients with IBD. We used multivariable regression to analyze associations between eleven non-IBD comorbidities and a composite primary outcome of COVID-19-related hospitalization or death. Comorbidities were first modeled individually, adjusting for potential confounders. Next, to determine the independent effect of comorbidities, we fit a model including all comorbidities as covariates. Results We analyzed 2,035 patients from 58 countries (mean age 42.7 years, 50.6% male). A total of 538 patients (26.4%) experienced severe COVID-19. All comorbidities but a history of stroke and obesity were associated with severe infection in our initial analysis, with adjusted odds ratios ranging from 1.9 to 3.7. In a model including all comorbidities significantly associated with the composite outcome in the initial analysis, as well as other confounders, most comorbidities remained significant, with the highest risk in chronic kidney disease and chronic obstructive pulmonary disease. Conclusion Many non-IBD comorbidities are associated with a two to threefold increased risk of COVID-19 hospitalization or death among patients with IBD. These data can be used to risk-stratify and guide treatment and lifestyle decisions during the ongoing pandemic

Characteristics and Outcomes of IBD Patients with COVID-19 on Tofacitinib Therapy in the SECURE-IBD Registry

The coronavirus disease 2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented loss of life and health on a global scale. COVID-19 outcomes are more severe among those with comorbid conditions, which raises concerns for patients with inflammatory bowel disease (IBD), especially given the increased infection risk with immunosuppression used for IBD therapy

Development and validation of multivariable prediction models for adverse COVID-19 outcomes in patients with IBD

Objectives Develop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD). Design and setting This study developed and validated prognostic penalised logistic regression models using reports to the international Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease voluntary registry from March to October 2020. Model development was done using a training data set (85% of cases reported 13 March–15 September 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported 16 September–20 October 2020). Participants We included 2709 cases from 59 countries (mean age 41.2 years (SD 18), 50.2% male). All submitted cases after removing duplicates were included. Primary and secondary outcome measures COVID-19 related: (1) Hospitalisation+: composite outcome of hospitalisation, ICU admission, mechanical ventilation or death; (2) Intensive Care Unit+ (ICU+): composite outcome of ICU admission, mechanical ventilation or death; (3) Death. We assessed the resulting models’ discrimination using the area under the curve of the receiver operator characteristic curves and reported the corresponding 95% CIs. Results Of the submitted cases, a total of 633 (24%) were hospitalised, 137 (5%) were admitted to the ICU or intubated and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set area under the curve (95% CI) of 0.79 (0.75 to 0.83) for Hospitalisation+, 0.88 (0.82 to 0.95) for ICU+ and 0.94 (0.89 to 0.99) for Death. Age, comorbidities, corticosteroid use and male gender were associated with a higher risk of death, while the use of biological therapies was associated with a lower risk. Conclusions Prognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of patients with IBD. A free online risk calculator (https://covidibd.org/covid-19-risk-calculator/) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with patients with IBD

Impact of Medications on COVID-19 Outcomes in Inflammatory Bowel Disease: Analysis of Over 6,000 Patients from an International Registry

The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, an international, collaborative database created to monitor COVID-19 outcomes in IBD patients, has previously reported that corticosteroids and mesalamine/sulfasalazine are associated with an increased risk of severe COVID-19 while tumor necrosis factor (TNF) antagonists do not impact risk.1 A follow-up report observed that patients on combination therapy with TNF antagonists and thiopurines appeared to be at higher severe COVID-19 risk.2 However, at that time the number of reported cases was too low to fully evaluate the risk of other IBD therapies. As the cases reported to SECURE-IBD have increased substantially, more granular analyses evaluating other IBD medication classes (including combination therapies) and adjusting for more covariates are possible. In this study, we compared associations between multiple medication classes and adverse COVID-19 outcomes in the SECURE-IBD database

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets