COVID-19 susceptibility and clinical outcomes in inflammatory bowel disease: An updated systematic review and meta-analysis.

The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI) = 0.28-1.18), 1.09 (95% CI = 0.27-4.47), and 0.67 (95% CI = 0.32-1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI = 0.38-0.74) and death (OR: 0.13; 95% CI = 0.13-0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.

Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era.

BACKGROUND: Studies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19). METHODS: This multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021. RESULTS: A total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn's disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn's disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020). CONCLUSION: Regardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.

Molecular mechanism of the TGF­ß/Smad7 signaling pathway in ulcerative colitis.

Aberrant TGF­ß/Smad7 signaling has been reported to be an important mechanism underlying the pathogenesis of ulcerative colitis. Therefore, the present study aimed to investigate the effects of a number of potential anti­colitis agents on intestinal epithelial permeability and the TGF­ß/Smad7 signaling pathway in an experimental model of colitis. A mouse model of colitis was first established before anti­TNF­α and 5­aminosalicyclic acid (5­ASA) were administered intraperitoneally and orally, respectively. Myeloperoxidase (MPO) activity, histological index (HI) of the colon and the disease activity index (DAI) scores were then detected in each mouse. Transmission electron microscopy (TEM), immunohistochemical and functional tests, including Evans blue (EB) and FITC­dextran (FD­4) staining, were used to evaluate intestinal mucosal permeability. The expression of epithelial phenotype markers E­cadherin, occludin, zona occludens (ZO­1), TGF­ß and Smad7 were measured. In addition, epithelial myosin light chain kinase (MLCK) expression and activity were measured. Anti­TNF­α and 5­ASA treatments was both found to effectively reduce the DAI score and HI, whilst decreasing colonic MPO activity, plasma levels of FD­4 and EB permeation of the intestine. Furthermore, anti­TNF­α and 5­ASA treatments decreased MLCK expression and activity, reduced the expression of Smad7 in the small intestine epithelium, but increased the expression of TGF­ß. In mice with colitis, TEM revealed partial epithelial injury in the ileum, where the number of intercellular tight junctions and the expression levels of E­cadherin, ZO­1 and occludin were decreased, all of which were alleviated by anti­TNF­α and 5­ASA treatment. In conclusion, anti­TNF­α and 5­ASA both exerted protective effects on intestinal epithelial permeability in an experimental mouse model of colitis. The underlying mechanism may be mediated at least in part by the increase in TGF­ß expression and/or the reduction in Smad7 expression, which can inhibit epithelial MLCK activity and in turn reduce mucosal permeability during the pathogenesis of ulcerative colitis.

Mesalazine induced interstitial pneumonitis in the COVID era.

Mesalazine is the most widely used aminosalicylate for induction and maintenance of remission in patients with mild-to-moderate ulcerative colitis (UC). Drug-induced hypersensitivity pneumonitis is considered very rare (<1/10.000 patients). Due to its rarity and the scarce cases reported, mesalazine-induced lung injury needs to be highly suspected in a patient with onset of respiratory symptoms and UC under treatment with salicylates. It should make the clinician formulate a differential diagnosis that includes not only infections (tuberculosis, bacterial...) or the inflammatory bowel disease itself, but also the current coronavirus disease 2019 (COVID-19) since their clinical and radiological manifestations may be very similar.

Mesalazine in Inflammatory Bowel Disease and COVID-19: Hospitalization and Adverse In-Hospital Outcomes Based on Nationwide Data.

BACKGROUND: We assessed whether 5-aminosalicylic acid (5-ASA), as treatment for inflammatory bowel disease (IBD), was associated with an increase in hospitalization for coronavirus disease 2019 and adverse in-hospital outcomes. METHODS: This was a Danish nationwide register study. The study population consisted of all patients with an IBD diagnosis between March 1, 2010, and March 1, 2020, and living in Denmark on March 1, 2020. Patients with IBD treated with 5-ASA (exposed) were compared with patients not receiving 5-ASA (unexposed). RESULTS: We identified 60 242 patients with IBD; 15 635 (40.5%) with ulcerative colitis (UC) and 964 (4.5%) with Crohn's disease (CD) were exposed to 5-ASA. For patients with UC who were 5-ASA exposed, the hazard ratio of hospitalization was 1.18 (95% confidence interval, 0.79-1.78). In-hospital outcomes were not statistical significant from those not exposed to 5-ASA (median length of hospital stay 5.6 days vs 7.2 days), mechanical ventilation (0% vs 14%), continuous positive airway pressure (7.9% vs 9.4%), and in-hospital mortality (21.1% vs 17.2%). For patients with CD, the hazard ratio of hospitalization was 2.25 (95% confidence interval, 1.02-4.97). We found no statistically significant difference in length of hospital stay (7.1 days vs 3.9 days), mechanical ventilation (0% vs 1.8%), use of continuous positive airway pressure (0% vs 1.8%), or in-hospital mortality (0% vs 9%) between exposed and unexposed patients. CONCLUSIONS: Patients with UC, treated with 5-ASA, had no increased risk of hospitalization for coronavirus disease 2019 or more adverse in-hospital outcomes. In patients with CD, 5-ASA may be associated with an increased risk of hospitalization but not with more adverse in-hospital outcomes.

In this national register study, 5-aminosalicylic acid (5-ASA)­treated ulcerative colitis patients had no increased risk of hospitalization for coronavirus disease 2019 (COVID-19) or more adverse in-hospital outcomes compared with patients not treated with 5-ASA. Also, 5-ASA­treated patients with Crohn's disease did not have more adverse in-hospital outcomes.

COVID-19 and Outcomes in Patients With Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Our understanding of coronavirus disease 2019 (COVID-19) and its implications for patients with inflammatory bowel diseases (IBD) is rapidly evolving. We performed a systematic review and meta-analysis to investigate the epidemiology, clinical characteristics, and outcomes in IBD patients with COVID-19. METHODS: We searched PubMed, EMBASE, Cochrane Central, Clinicaltrials.gov, Web of Science, MedRxiv, and Google Scholar from inception through October 2020. We included studies with IBD patients and confirmed COVID-19. Data were collected on the prevalence, patient characteristics, pre-infection treatments for IBD, comorbidities, hospitalization, intensive care unit (ICU), admission, and death. RESULTS: Twenty-three studies with 51,643 IBD patients and 1449 with COVID-19 met our inclusion criteria. In 14 studies (n = 50,706) that included IBD patients with and without COVID-19, the prevalence of infection was 1.01% (95% confidence interval [CI], 0.92-1.10). Of IBD patients with COVID-19, 52.7% had Crohn's disease, 42.2% had ulcerative colitis, and 5.1% had indeterminate colitis. Nine studies (n = 687) reported outcomes according to IBD therapy received. Compared with patients on corticosteroids, those on antitumor necrosis factor (anti-TNF) therapy had a lower risk of hospitalization (risk ratio [RR], 0.24; 95% CI, 0.16-0.35; P < .01; I2 = 0%) and ICU admission (RR, 0.10; 95% CI, 0.03-0.37; P < .01) but not death (RR, 0.16; 95% CI, 0.02-1.71; P = .13; I2 = 39%). Compared with patients on mesalamine, those on antitumor necrosis factor therapy had a lower risk of hospitalizations (RR, 0.37; 95% CI, 0.25-0.54), ICU admissions (RR, 0.20; 95% CI, 0.07-0.58), and death (0.21; 95% CI, 0.04-1.00). Comparing patients on immunomodulators vs mesalamine or anti-TNF therapy, there was no difference in these outcomes. CONCLUSIONS: The prevalence of COVID-19 in IBD patients was low. Use of corticosteroids or mesalamine was significantly associated with worse outcomes, whereas use of anti-TNFs was associated with more favorable outcomes. Further investigation clarifying the mechanisms of these disparate observations could help identify risk and adverse outcome-mitigating strategies for patients with IBD.

A machine learning approach identifies 5-ASA and ulcerative colitis as being linked with higher COVID-19 mortality in patients with IBD.

Inflammatory bowel diseases (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammation within the gastrointestinal tract. IBD patient conditions and treatments, such as with immunosuppressants, may result in a higher risk of viral and bacterial infection and more severe outcomes of infections. The effect of the clinical and demographic factors on the prognosis of COVID-19 among IBD patients is still a significant area of investigation. The lack of available data on a large set of COVID-19 infected IBD patients has hindered progress. To circumvent this lack of large patient data, we present a random sampling approach to generate clinical COVID-19 outcomes (outpatient management, hospitalized and recovered, and hospitalized and deceased) on 20,000 IBD patients modeled on reported summary statistics obtained from the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD), an international database to monitor and report on outcomes of COVID-19 occurring in IBD patients. We apply machine learning approaches to perform a comprehensive analysis of the primary and secondary covariates to predict COVID-19 outcome in IBD patients. Our analysis reveals that age, medication usage and the number of comorbidities are the primary covariates, while IBD severity, smoking history, gender and IBD subtype (CD or UC) are key secondary features. In particular, elderly male patients with ulcerative colitis, several preexisting conditions, and who smoke comprise a highly vulnerable IBD population. Moreover, treatment with 5-ASAs (sulfasalazine/mesalamine) shows a high association with COVID-19/IBD mortality. Supervised machine learning that considers age, number of comorbidities and medication usage can predict COVID-19/IBD outcomes with approximately 70% accuracy. We explore the challenge of drawing demographic inferences from existing COVID-19/IBD data. Overall, there are fewer IBD case reports from US states with poor health ranking hindering these analyses. Generation of patient characteristics based on known summary statistics allows for increased power to detect IBD factors leading to variable COVID-19 outcomes. There is under-reporting of COVID-19 in IBD patients from US states with poor health ranking, underpinning the perils of using the repository to derive demographic information.

COVID-19 in IBD: The experience of a single tertiary IBD center.

BACKGROUND: Italy has been one of the most affected countries in the world by COVID-19. There has been increasing concern regarding the impact of COVID-19 on patients with inflammatory bowel disease (IBD), particularly in patients treated with immunosuppressants or biologics. The aim of our study is to understand the incidence of COVID-19 in a large cohort of patients with IBD. Furthermore, we analyzed possible risk factors for infection and severity of COVID-19. METHODS: This was an observational study evaluating the impact of COVID-19 on IBD patients in a single tertiary center. A 23 multiple-choice-question anonymous survey was administered to 1200 patients with IBD between March 10th and June 10th 2020. RESULTS: 1158 questionnaires were analyzed. The majority of patients had Crohn's disease (CD) (60%) and most of them were in clinical remission. Among the 26 patients (2.2%) who tested positive for COVID-19, only 5 (3CD) were on biological treatment and none required hospitalization. Two patients died and were on treatment with mesalazine only. Of the 1158 patients, 521 were on biological therapy, which was discontinued in 85 (16.3%) and delayed in 195 patients (37.4%). A worsening of IBD symptoms was observed in 200 patients on biological therapy (38.4%). Most of these patients, 189 (94.5%), had stopped or delayed biological treatment, while 11 (5.5%) had continued their therapy regularly (p<0.001). CONCLUSIONS: Our data are in line with the current literature and confirm a higher incidence compared to the general population. Biological therapy for IBD seems to not be a risk factor for infection and should not be discontinued in order to avoid IBD relapse.

De-escalation of medical therapy in inflammatory bowel disease.

Treatment strategies for inflammatory bowel disease (IBD) now increasingly target deep remission, yet the resultant more aggressive use of medical therapy is associated with potentially serious adverse events and significant costs. It is, therefore, of vital importance to consider when, how and in whom medical therapy may be safely de-escalated. This issue is of great potential relevance in the current SARS-Cov-2 pandemic. In this review, we first discuss the rationale for drug withdrawal in IBD, before considering the available data on withdrawal of 5-aminosalicylates (5-ASA), immunomodulators (IM) and biological therapy in both ulcerative colitis (UC) and Crohn's Disease (CD). We consider how to identify patients most appropriate for drug withdrawal and outline a potential monitoring strategy for the early detection of relapse following drug withdrawal. We conclude with important future perspectives in this challenging field, and highlight ongoing trials that are likely to shape practice in the years to come.

Benign Evolution of SARS-Cov2 Infections in Children With Inflammatory Bowel Disease: Results From Two International Databases.

The coronavirus disease 2019 (COVID-19) pandemic caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents most often with mild clinical symptoms, but the severe forms are of major concern.1 SARS-CoV-2 enters human cells via the angiotensin-converting enzyme 2 receptor, expressed on epithelial and endothelial cells.2 Because the highest angiotensin-converting enzyme 2 expression is in the terminal ileum and colon, and up-regulated further during inflammation, and many COVID-19 patients experience gastrointestinal symptoms, longitudinal data are necessary to determine whether inflammatory bowel disease (IBD) patients are at risk for severe or complicated COVID-19. A recent analysis in IBD patients from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry showed older age, steroid medication, and comorbidities as risk factors for severe evolution, and the same study showed that the 29 IBD patients younger than age 20 had only mild disease courses.3 This report describes the disease course of COVID-19 in an expanded sample of pediatric IBD patients from 2 international databases.