key: cord-0737886-bayabroa authors: Brenner, Erica J.; Pigneur, Bénédicte; Focht, Gili; Zhang, Xian; Ungaro, Ryan C.; Colombel, Jean-Frederic; Turner, Dan; Kappelman, Michael D.; Ruemmele, Frank M. title: BENIGN EVOLUTION OF SARS-CoV2 INFECTIONS IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE: RESULTS FROM TWO INTERNATIONAL DATABASES date: 2020-10-12 journal: Clin Gastroenterol Hepatol DOI: 10.1016/j.cgh.2020.10.010 sha: 1ef8eae045568f2db319d46f5f1588ac41ca2c62 doc_id: 737886 cord_uid: bayabroa nan The coronavirus disease 2019 (COVID-19) pandemic caused by the highly infectious severe acute respiratory syndrome coronavirus2 (SARS-CoV2) presents most often with mild clinical symptoms, but the severe forms are of major concern. 1 SARS-CoV2 enters human cells via the angiotensin-converting enzyme 2 (ACE2) receptor, expressed on epithelial and endothelial cells. 2 Since highest ACE2 expression is in the terminal ileum and colon, further upregulated during inflammation, and many COVID-19 patients experience gastrointestinal symptoms, longitudinal data are necessary determine whether inflammatory bowel diseases (IBD) patients are at risk for severe or complicated COVID-19. A recent analysis in IBD patients from the SECURE-IBD registry revealed older age, steroid medication and comorbidities as risk factors for severe evolution, while the same study showed that the 29 IBD patients less 20 years had only mild disease courses. 3 The purpose of this report is to describe the disease course of COVID-19 in an expanded sample of pediatric IBD patients from two international databases. Bowel Disease (SECURE-IBD) and the COVID-19 database of the Paediatric IBD Porto group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) were created in March 2020 with the aim to monitor outcomes of COVID-19 occurring in IBD patients. In this analysis, we included all subjects ≤18 years of age from the SECURE-IBD and Porto Group databases through October 1 st , 2020. We used descriptive statistics to summarize the demographic and disease characteristics of the study population, both overall and stratified by hospitalization status (hospitalized versus outpatient only), and performed bivariate comparisons (see Supplemental Methods). We collected 209 COVID-19 cases in PIBD patients from 23 countries ( Table 1 ). The most common IBD treatment was TNF antagonist monotherapy (48%), followed by sulfasalazine/mesalamine (23%). Most patients (86%) had no comorbidities other than IBD. There were no deaths in the study population, and fourteen children (7%) were hospitalized, of whom only two (1%) required mechanical ventilation. The two children requiring mechanical ventilation were on sulfasalazine/mesalamine and developed a multi-system inflammatory syndrome and concomitant secondary infection, respectively, with favorable evolution. Characteristics of the fourteen hospitalized patients are provided in Supplemental Table 1 . Factors associated with hospitalization included comorbid conditions other than IBD (50% hospitalized vs 12% not; p value <0.01), moderate/severe IBD disease activity (64% vs 15%; p value <0.01 overall), gastrointestinal symptoms (71% vs 19%, p value <0.01), sulfasalazine/mesalamine use (57% vs 21%; p value 0.01), and steroid use (29% vs 8%, p value 0.03). TNF antagonist monotherapy was associated with a decreased likelihood of hospitalization (7% vs 51%; p value <0.01) ( Table 1 ). Sulfasalazine/mesalamine use remained a risk factor after adjusting for disease activity (aOR 4.2, 95% confidence interval 1.3-14.1) We analyzed 209 children and adolescents ≤18 years with PIBD who developed COVID-19. The 7% hospitalization rate found here is markedly less than 33-66% hospitalization reported in adult IBD patients. 3, 4 Our data are in line with other reports indicating that children are at low risk for complicated COVID-19. 5 Reported cases likely under-represent the actual case burden, since most paediatric COVID-19 manifestations are mild or asymptomatic and SARS-CoV2 testing is not indicated. A case series of 1,213 children found that 55.9% of cases were asymptomatic or mild, and only 5.9% were severe. 5 Additionally,mild cases may be under-reported. Thus, the low observed hospitalization rate is likely an overestimation of the true hospitalization rate. The findings that sulfasalazine/mesalamine and steroid use were associated with increased hospitalization risk and that TNF antagonist monotherapy was associated with decreased risk parallel those reported in adult IBD patients. 3 Other risk factors for hospitalization included other comorbid conditions, moderate/severe IBD disease activity, and gastrointestinal symptoms. The six-year-old colitis patient requiring ICU care in this series is in line with the recent reports of multi-systemic inflammatory (Kawasaki-like) syndrome temporarily related to SARS-CoV-2 infection in children. 6 Our patient had a favourable evolution with steroid medication, while a recently reported 14-year-old boy with CD also developing a Kawasakilike syndrome had an immediate improvement with infliximab medication. 7 The other ICUlevel patient developed a secondary infection that required multiple antimicrobial agents. In conclusion, our data suggest PIBD patients have a relatively low risk of severe COVID-19, even when receiving biologic and/or other immune suppressive therapies for their IBD. This finding may reassure parents of children with IBD who are debating the safety of sending their children back to school in the fall. These data support earlier guidance from the Pediatric Porto group to continue maintenance IBD treatment for PIBD throughout the current pandemic. J o u r n a l P r e -p r o o f (7) 26 (14) 143 (77) 17 ( Case details were reported directly by providers using case report forms created in REDCap (Research Electronic Data Capture), a secure, web-based electronic data capture tool, as has been previously described. 1, 2 We removed duplicate reports known to have been entered into both databases. Additionally, we double checked for duplicate reports by identifying records with matching age, sex, IBD disease type, and country. Potential duplicates were manually reviewed, and true duplicates were removed. Incomplete reports with missing outcome data were excluded from analysis. Disease activity was assessed by Physician Global Assessment (PGA), and comorbid conditions were defined as any chronic condition beyond IBD as determined by the reporter. We summarized continuous variables using means and standard deviations. We expressed categorical variables as number of participants and proportions. We performed bivariate comparisons by hospitalization status using the Fisher's exact test for each categorical variable and the t-test for continuous variables. We listed demographic and disease characteristics for all cases that required hospitalization. A Novel Coronavirus from Patients with Pneumonia in China Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry novel coronavirus disease (COVID-19) in patients with inflammatory bowel diseases Epidemiology of COVID-19 Among Children in China Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab ) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry ) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition We performed a post-hoc logistic regression evaluating the association between mesalamine/sulfasalazine and hospitalization with adjustment for IBD disease activity by PGA. We reported the adjusted odds ratio and 95% confidence interval.The databases were constructed and maintained according to the local ethics instructions/committees. J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f