The incidence and clinical characteristics of COVID-19 in children with IBD during the Omicron Wave: a single-center experience in China

The incidence and clinical characteristics of COVID-19 in children with IBD during the Omicron Wave: a single-center experience in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The incidence and clinical characteristics of COVID-19 in children with IBD during the Omicron Wave: a single-center experience in China Rui Li, Pei-Yu Chen, Hui-Wen Li, Lu Ren, Yang Cheng, Li-Ying Liu, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3765503/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aims The pandemic of Coronavirus disease 2019 (COVID-19) had a major impact on the health of people worldwide, including the pediatric inflammatory bowel diseases (PIBD) patients. As no study has investigated the susceptibility and disease course of COVID-19 in PIBD patients after the end of zero-COVID policy in China, we conducted a retrospective cross-sectional study in our center. Methods A cross-sectional survey enrolling PIBD patients has been completed by online survey, phone, and face-to-face assessment. The demographic data, epidemiological characteristics, clinical manifestations, treatment and prognosis of the patients were analyzed. Results PIBD patients represented 55.45%(56/101) of SARS-CoV-2 positive cases between December 1st 2022 and January 31th 2023, 67.86% were male, mean age was 11.15 ± 3.92 years old. Among the SARS-CoV-2 positive cases, 3 patients (5.36%) were asymptomatic, 53 patients (94.64%) had mild symptoms. The main symptoms were fever (92.86%), cough (69.64%), nasal congestion or runnig nose (35.71%), and sore throat (33.93%). No severe case or deaths were reported. All patients recovered from COVID-19 symptoms within one week. We did not observe an association between different clinical disease activities and SARS-CoV-2 infection rates, so as it in different treatments. 51 patients were reported to be in close contact with persons confirmed with COVID-19 infection, and out of them, 36 patients test positive of SARS-CoV-2, which is significantly higher than it in patients without exposure of COVID-19 (70.59% vs. 33.33%, p = 0.002). A total of 10 patients were underweight, of which 9 patients tested positive for COVID-19( p = 0.048). Meanwhile, unvaccinated patients were also found to be more susceptible to SARS-CoV-2 than vaccinated patients(70.97% vs. 48.48%, p = 0.049). Conclusions The incidence of SARS-CoV-2 infection in our center of pediatric IBD patients during the Omicron pandemic was 55.45%. No severity or death case was observed. Patients with underweight, unvaccinated and history of exposure to COVID-19 were at higher risk of SARS-CoV-2 infection. COVID-19 inflammatory bowel disease pediatric incidence disease course risk factors cross-sectional study Figures Figure 1 Figure 2 1. Introduction The coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, is an acute infectious respiratory syndrome first reported in December 2019 [ 1 ] . It exponentially spread across all continents in just a few weeks and brought great challenges to global public health [ 2 ] . The World Health Organization has defined five variants of SARS-CoV-2 (VoC) of concern, named Alpha, Beta, Gamma, Delta, and Omicron. Since its identification in November 2021, the Omicron variant has spread rapidly around the globe and cause large outbreaks in children and adolescents [ 3 – 6 ] . It has been reported that immunocompromised patients are at increased risk of severe illness and mortality from infection, and serious complications may occur in children, especially those with chronic and underlying conditions [ 7 ] . Characterized by immune-mediated chronic inflammation of the gastrointestinal tract, patients with inflammatory bowel disease (IBD) get increasing concern about the impact of COVID-19. Whether disease activity and biological treatment are risk factors for COVID-19 in IBD patients remains controversial [ 6 , 8 ] . The actual risk of infection or development of COVID-19 in these at-risk patients with IBD is not clear, particularly in children and adolescents treated with immunosuppressants or biologics. In the past few years, China has responded by implementing non-pharmaceutical interventions (NPIs) with a series of public health and social measures, so called zero-COVID policy. After the announcement of “20 measures” in December 2022, the management of COVID-19 has been downgraded from Class A to Class B in accordance with the country's law on infectious diseases prevention and treatment, meaning the end of zero-COVID policy and the enterance to a new phase of the COVID-19 response [ 9 ] . In this new phase of the pandemic, China is facing unprecedented challenges, so do the IBD children. With this in mind, we investigate the epidemiology, clinical characteristics, and outcomes of COVID-19 in PIBD patients. We conducted a cross-sectional study among the PIBD patients in our tertiary IBD center, in the first month following the transition of prevention policy, all IBD patients younger than 18 years old were included. 2. Materials and methods To evaluate the impact of COVID-19 on PIBD patients, after the approval of the ethics committee of the Guangzhou Women and Children's Medical Center, we conducted a retrospective cross-sectional study among PIBD patients followed in our center. All patients were individually contacted by online survey, phone, and face-to-face assessment between December 1st 2022 and January 31st 2023. Patients younger than 18 years old who were diagnosed as IBD were eligible for this study. The flow diagram of the included patients is demonstrated in Fig. 1 . An online survey was conducted in Chinese by the Questionnaire Star platform ( https://www.wjx.cn ). The questionnaire was filled in by the child's parents/caregivers, and the information of clinical manifestation and follow-up assessments were reconfirmed by gastroenterologists at our institution. The COVID-19 cases were confirmed according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 9) and WHO public health surveillance for COVID-19, the symptoms and severity of SARS-CoV-2 infection in children were classified as asymptomatic, mild, moderate and severe. Undernutrition of PIBD patients was described as thinness (low BMI-for-age), stunting (low height-for-age) and underweight (low weight-for-age) according to the WHO definition. The survey documents the data on demographics, diseases and conditions (including diagnosis, disease activity, and treatment), and information about COVID-19. Disease activity was calculated at the time of the last available clinical follow-up using pediatric Crohn's disease (CD) and ulcerative colitis (UC) activity indexes. All patients were asked to describe if they experienced subjective worsening of IBD symptoms and details for hospitalized patients during COVID-19. COVID-19 outcomes were classified as outpatient care, hospitalization, ventilator requirement, and death from COVID-19 or related complications. Written informed consent was obtained from the parents of the included children during the primary data collection process. All data used in this study were again to verify by gastroenterologists. 3. Statistical analysis Descriptive statistics were calculated for the basic demographic and clinical characteristics of the study population. Continuous variables were summarized as means and standard deviations, and categorical variables as proportions. The differences between groups were compared using the Mann-Whitney U test, Kruskal-Wallis H test, and Student's t-test, as appropriate. The chi-square test or Fisher's exact test was used to examine the differences between groups when the cell numbers were less than five. All statistical analyses were performed using a statistical software package (SPSS-20). Two-sided p values < 0.05 were considered statistically significant. 4. Results 4.1 Demographics and Characteristics of the IBD Children A total of 101 questionnaires were analyzed, 56 of them test positive of SARS-CoV-2, which means the incidence of SARS-CoV-2 infection was 55.45%. Demographic, clinical characteristics of pediatric IBD patients with SARS-CoV-2 test are summarized in Table 1 . The mean age of PIBD patients was 11.08 years (± 4.14). As expected, most patients were male (65.35%). It is the same in SARS-CoV-2 infected patients (67.86%). The difference of COVID-19 incidence between male and female pediatric IBD patients was no significant. Patients with CD account for the majority of PIBD(91.09%), and most of IBD patients were in clinical remission(51.49%) [ 10 ] . Among the 56 IBD patients who tested positive for SARS-CoV-2, 52 were CD, 1 was UC, and 3 were unclassified colitis. According to the Paris classification, we classified age at diagnosis as 0 to < 10 years and 10 to < 17 years, the rate of SARS-CoV-2 infection was about the same between two groups. Of all patients, the mean duration of disease was 2.54 years, the longest was 10 years. As recorded in Table 1 , the nutritional status of IBD children was divided into three subgroups based on the definition of WHO growth reference. Within the cohort, 14(13.86%) patients were wasting, 6(5.94%) patients were stunting, and 10(9.9%) patients were underweight. It's worth noting that 9 out of 10 patients who were underweight got SARS-CoV-2 infection, which showed a statistic difference on incidence of COVID-19 between PIBD patients with and without underweight( p = 0.048). Of the included children, 61 patients (60.40%) were on biological treatment, 5 were on mesalazine, 6 were on thiopurines and 3 were on steroids. Of the 61 patients on biological therapy, 40 were on infliximab, 20 were on adalimumab, and 1 was on ustekinumab. To be noticed, 9 patients were in combo-therapy (3 were on anti-TNF-α treatment together with thalidomide, 2 were on anti-TNF-αtreatment and thiopurines, 1 was on thalidomide and mesalazine, 1 was on anti-TNF-α treatment together with mesalazine, 1 was on steroids and mesalazine, 1 was on steroids and thiopurines). There were no significant differences in the incidence of COVID-19 between different treatments. 1 patient confirmed to have IL-10 receptor A (IL-10 RA) defect, 1 patient had comorbidity of immunodeficiency. 51 patients were reported to be in close contact with persons confirmed with COVID-19 infection, out of them, 70.59% patients test positive of SARS-CoV-2, which is significantly higher than it in patients without COVID-19 exposure (70.59% vs. 33.33%, p = 0.002). 4.2 Clinical manifestation of SARS-CoV-2 infection in children with IBD Among the 56 IBD patients who tested positive for SARS-CoV-2, 53(94.64%) patients presented with mild symptoms, 3(5.36%) were asymptomatic. No one was classified with moderate and severe COVID-19, and no patient died. List of symptoms was summarized in Fig. 2 . The most common symptoms were fever (92.86%), mean duration was 1.84 days. The top five most common symptoms among symptomatic cases were fever(92.86%), cough(69.64%), rhinobyon and running nose(35.71%), sore throat (33.93%), and fatigue(26.79%). Because of the popularization of COVID-19 knowledge, 45 of our patients (80.36%) didn’t need medical consultation, 10(17.86%) patients need outpatient care, and only 1 (1.78%) mild COVID-19 patient was hospitalized for 3 days. 4.3 Vaccination status and Worsen of IBD symptoms Among the 101 children IBD patients involved, 97 patients were eligible for COVID-19 vaccination (aged ≥ 3 years), 31(31.96%) were unvaccinated. A total of 66(68.04%) patients received at least one dose of vaccination. The incidence of SARS-CoV-2 infection on unvaccinated patients and vaccinated patients were 70.97% and 48.48%, which showed a higher incidence of SARS-CoV-2 infection in unvaccinated patients ( p = 0.049). In our cohort, the incidence of SARS-CoV-2 infection didn’t show significant difference between different disease activities in IBD. Among the 101 patients with IBD included in our cohort, 32(14.6%) had spontaneously interrupted their therapy because infection of SARS-CoV-2, all of them treated with immunosuppressors and biologics. Finally, the incidence of SARS-CoV-2 infection was 55.45% in whole pediatric IBD population. 5. Discussion Data about the incidence and its disease course of COVID-19 among patients with IBD remain scarce, especially in children and adolescents. We conduct the the first population-based study of COVID-19 among pediatric IBD patients and the first cross-sectional study after the end of the zero-COVID policy in China. A total of 101 IBD children were included, the majority of them had CD (91.09%), and there was a slight predominance of males. Almost half of our patients were in clinical remission (51.49%). 56 patients were found SARS-CoV-2 infection. The estimated incidence is 55.45%, which is much lower than that of the overall population in Guangzhou(༞85%) reported on the press conference on Jan 18 [ 11 ] . Even so, the incidence is significantly higher than it in other reports [ 12 – 14 ] . In addition, 11 patients were defined as highly suspected of COVID-19, which of whom presented influenza-like symptoms and closely contacted with confirmed cases, but didn’t have SARS-COV-2 test. The incidence of SARS-CoV-2 infection might be underestimated because of the suboptimal sensitivity of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 and the difficulty of getting tested [ 15 ] . Some studies indicate a higher risk of COVID-19 and mortality in patients with IBD, while some had the opposite conclusion [ 16 – 19 ] . In our cohort, the incidence of COVID-19 in IBD population is much lower than it in the general population [ 20 ] , and a relatively small proportion of patients requiring hospitalization. No patient got severe COVID-19, and no deaths have been observed. There are reports showed that the strength of the association between active IBD and adverse outcomes varied with age and was greatest in younger patients, the association between severe clinical disease activity and COVID-19 outcomes was seen in patients ≤ 50 years [ 21 ] . In this study, we did not observe an association between clinical disease activity and the severity or incidence of COVID-19. It can also be explained that Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection [ 22 ] . Studies show that young children under 5 years of age and patients with comorbidity have increased risk of getting COVID-19 [ 23 ] . However, in our study, 13 patients were younger than 5 years-old, the infection rate of SARS-CoV-2 was about the same as it in other age group. Of the 101 patients included, 60.40% were on biologic therapy, mostly were anti-TNF-α therapy. We didn’t observe a significant statistical difference in the incidence of COVID-19 in patients treated with or without biologic therapy. Patients treated with biologics had a favorable outcome, which is consistent with former reports [ 8 ] . In this study population, no severe course of COVID-19 was observed, symptoms reported by all patients were mild (mostly fever and cough). In our observation, we did not identify any association between COVID-19 infection rates or risk of severe course and IBD-related treatment, which was consistent with previous reports [ 12 , 24 ] . Constanze reported TNF-inhibitors and ustekinumab show a protective role in preventing respiratory tract infections among older age (> 49 years) [ 25 ] , and Lev also reported that patients who received biologics had a significantly milder course of disease [ 8 ] . The most frequent symptom in our cohort is fever, followed by cough, nasal symptoms, and sore throat, which is in common with the study of De Souza [ 26 ] . They described the clinical characteristics of 1124 cases of children with COVID-19, fever was the most prevalent symptom, followed by cough, nasal symptoms, diarrhea, nausea, vomiting, fatigue, and respiratory distress. Among the included patients, 22(21.78%) were undernutrition, 10 of them were underweight. Notably, 9 out of 10 underweight patients got SARS-CoV-2 infection. Reports showed that patients with higher nutrition risk have worse outcome [ 27 ] . In a large multiethnic cohort study of adults hospitalized with COVID-19, they found that patients who were underweight and those with BMIs above the overweight range were more likely to be intubated or die [ 28 ] . These studies showed the association between underweight and poor outcomes of COVID-19 [ 29 ] . As in our study, we observe a significant high rate of SARS-CoC-2 infection in underweight PIBD patient, but all of them did not get severe course of COVID-19. Future studies should be performed between the body mass and outcomes of COVID-19. Several preliminary studies have found a reduced risk of hospitalisation and severe outcomes for omicron relative to the delta variant of SARS-CoV-2 [ 30 ] . By evaluating neutralizing antibody response in a comparator group of children, who were vaccinated with two doses or a single dose of mRNA vaccine, Juanjie Tang found that largest reduction (25.2-fold) of neutralization titers in vaccinated children was observed against the Omicron variant [ 31 ] . However, importantly, all 8 of the 9 children who received two doses of mRNA vaccine still showed Pseudovirion neutralization assay (PsVNA) 50 titers (for a sample dilution that resulted in 50% virus neutralization) > 1:20 against Omicron. Vaccine induced a much broader neutralizing antibody response against SARS-CoV-2 variants of concern (VOCs) in naive children compared with the natural immunity induced following SARS-CoV-2 infection. Studies showed that a moderate vaccine effectiveness after 2 doses of BNT162b2 or CoronaVac in children and adolescents, and third doses of either BNT162b2 or CoronaVac provide substantial additional protection against severe COVID-19 [ 32 , 33 ] . Studies have shown that COVID-19 vaccine effectiveness in IBD patients is comparable with that in non-IBD controls [ 34 ] . But several researches showed that anti-TNF-α treatment have attenuated response to vaccination against COVID-19. A multicentre, prospective, case-control study in UK also indicated the prioritization of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF-α and JAK inhibitors [ 35 – 37 ] . These studies underscored the importance of vaccination. A systematic review and meta-regression study showed that vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21.0 percentage points among people of all ages [ 38 ] . In our study, 66 patients got vaccinated, only 7 patients got booster vaccination, and most of our patients got last vaccination for more than 6 months before the Omicron wave. Among the patients who were eligible for COVID-19 vaccination, a higher risk of SARS-CoV-2 infection was found in unvaccinated patients than it in vaccinated patients. This result shows that even over 6 months after vaccination, COVID-19 vaccine remained efficient against SARS-CoV-2 infection. Some studies reported that a complication of gastrointestinal disease observed in children is multisystem inflammatory syndrome in children (MIS-C), which included abdominal pain, diarrhea, ongoing fever, cardiac dysfunction and multiple organ failure [ 39 ] . We observed 16 patients had gastrointestinal symptoms, no one had MIS-C. There were some studies suggest that this imbalance in immune homeostasis especially in patients with severe COVID-19 has been linked to gastrointestinal symptoms such as diarrhea [ 40 ] . Various etiopathogenetic hypotheses have been advanced to explain the occurrence of diarrhea in COVID-19 patients, including loss in enterocyte absorption capability, microscopic mucosal inflammation damage, and an impaired function of ACE2, which leads to a downstream dysbiosis and metabolite imbalance [ 41 – 45 ] . As for our patients, there was no apparent aggravation of diarrhea compare to general patients. Former research showed that patients who discontinued or delayed therapy with anti-TNF-α agents or other biologics had a higher rate of relapse [ 12 , 46 ] . In our cohort, none of our patients modified the current treatment regimen, while 42.57% delayed or withheld it because of the epidemic. The main reasons of delay were the infection of COVID-19. In this study, we performed the first population-based study of SARS-CoV-2 infection among pediatric IBD patients in China, furthermore, the first study after the end of the zero-COVID policy. Second, we included 101 pediatric IBD patients in our institution, the data records are detailed. Third, we observe a higher rate of SARS-CoV-2 infection in underweight pediatric IBD patients, and ≥ 1 dose of vaccination against infection was efficient against SARS-CoV-2 infection. Nonetheless, some limitations must be taken into consideration. First, pediatric IBD cases were included only in our institute, the small sample size of our cohort of patients prevent us from drawing any final conclusions on the risk factors of COVID-19 severity in the pediatric IBD population. Second, during the COVID-19 outbreak after the end of NPIs, a great number of COVID-19 patients caused the overrun of hospital. The lack of testing might underestimate the incidence of SARS-CoV-2 infection in IBD patients somewhat. Third, there was none severe COVID-19 case in our cohort that prevent us to identify risk factors related to the IBD demographic and treatment. 6. Conclusions In conclusion, we first reported the results of clinical data and incidence of SARS-Cov-2 infection in Chinese PIBD patients. The incidence of COVID-19 infection in our IBD cohort was 55.45%, which is found to be lower than general population. All patients had mild to no symptoms. We also observed a higher rate of SARS-CoV-2 infection in underweight or unvaccinated PIBD patients, which highlights the importance of nutrition management and vaccination in IBD children and adolescents. Further, follow-up study is necessary to help us conduct better strategies for children with IBD. Declarations Funding This work was supported by Guangzhou Medical Key Disciplines and Specialties(grand No.011006003) and Guangzhou Key Laboratory Bowel Disease(grand No.2023A03J0866). Author Contribution Rui Li contributed to conception and design, acquisition of data, data analysis and interpretation, and drafting of the manuscript. Lan-Lan Geng contributed to conception and design, data analysis and interpretation. All authors critically revised the manuscript, and approved the final version of the manuscript. Availability of Data and Materials: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. References Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. 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Bordalo FF, Rafael MA, Coimbra L, Boavida N, Arrobas F, Pereira CF, Martins FL, Carvalho EBJ, Carvalho LL, Santos L, Oliveira AM. Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease. Vaccine 2023 2023/6/13; 41(26): 3862–71. Doherty J, Morain NO, Stack R, Girod P, Tosetto M, Inzitiari R, Sheridan J, Cullen G, McDermott E, Buckley M, Horgan G, Mulcahy H, Ryan EJ, Daghfal D, Doran P, Morain CO, Doherty GA. Reduced Serological Response to COVID-19 Vaccines in Patients with IBD is Further Diminished by TNF Inhibitor Therapy; Early Results of the VARIATION study [VAriability in Response in IBD Against SARS-COV-2 ImmunisatiON]. J Crohns Colitis 2022 2022/9/8; 16(9): 1354–62. Alexander JL, Liu Z, Muñoz SD, Reynolds C, Ibraheim H, Anandabaskaran S, Saifuddin A, Castro SR, Anand N, Nice R, Bewshea C, D'Mello A, Constable L, Jones GR, Balarajah S, Fiorentino F, Sebastian S, Irving PM, Hicks LC, Williams H, Kent AJ, Linger R, Parkes M, Kok K, Patel KV, Teare JP, Altmann DM, Goodhand JR, Hart AL, Lees CW, Boyton RJ, Kennedy NA, Ahmad T, Powell N. COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study. Lancet Gastroenterol. 2022;2022/11/1(11):1005–15. Feikin DR, Higdon MM, Abu-Raddad LJ, Andrews N, Araos R, Goldberg Y, Groome MJ, Huppert A, O'Brien KL, Smith PG, Wilder-Smith A, Zeger S, Deloria KM, Patel MK. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet 2022 2022/3/5; 399(10328): 924–44. Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr 2021 2021/7/1; 180(7): 2019–34. Zhang L, Han C, Zhang S, Duan C, Shang H, Bai T, Hou X. Diarrhea and altered inflammatory cytokine pattern in severe coronavirus disease 2019: Impact on disease course and in-hospital mortality. J Gastroen Hepatol 2021 2021/2/1; 36(2): 421–9. Gu J, Han B, Wang J. COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission. Gastroenterology 2020 2020/5/1; 158(6): 1518–1519. Hikmet F, Méar L, Edvinsson Å, Micke P, Uhlén M, Lindskog C. The protein expression profile of ACE2 in human tissues. Mol Syst Biol 2020 2020/7/1; 16(7): e9610. Senapati S, Banerjee P, Bhagavatula S, Kushwaha PP, Kumar S. Contributions of human ACE2 and TMPRSS2 in determining host-pathogen interaction of COVID-19. J Genet 2021 2021/1/20; 100(1). Scaldaferri F, Ianiro G, Privitera G, Lopetuso LR, Vetrone LM, Petito V, Pugliese D, Neri M, Cammarota G, Ringel Y, Costamagna G, Gasbarrini A, Boskoski I, Armuzzi A. The Thrilling Journey of SARS-CoV-2 into the Intestine: From Pathogenesis to Future Clinical Implications. Inflamm Bowel Dis 2020 2020/8/20; 26(9): 1306–14. Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, Sigl V, Hanada T, Hanada R, Lipinski S, Wild B, Camargo SM, Singer D, Richter A, Kuba K, Fukamizu A, Schreiber S, Clevers H, Verrey F, Rosenstiel P, Penninger JM. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nat 2012 2012/7/25; 487(7408): 477–81. Turner D, Huang Y, Martín-de-Carpi J, Aloi M, Focht G, Kang B, Zhou Y, Sanchez C, Kappelman MD, Uhlig HH, Pujol-Muncunill G, Ledder O, Lionetti P, Dias JA, Ruemmele FM, Russell RK. Corona Virus Disease 2019 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastr Nutr 2020 2020/6/1; 70(6): 727–33. Tables Table 1 Demographics and clinical characteristics of pediatric IBD population. SARS-CoV-2 TEST p ALL (N = 101) Positive (N = 56) Negative (N = 45) Male, n(%) 66(65.35) 38(67.86) 28(62.22) NS Age, year (± SD) 11.08(±4.14) 11.15(±3.92) 10.96(±4.49) NS IBD classification, n(%) NS CD 92(91.09) 52(92.86) 40(55.89) UC 4(3.96) 1(1.78) 3(6.67) Unclassified 5(4.95) 3(5.36) 2(4.44) Age at the time of IBD diagnosis, n(%) NS ༜10y 50(49.50) 28(50.00) 22(48.89) 10-17y 51(50.50) 28(50.00) 23(51.11) IBD disease activity, n(%) NS Remission 52(51.49) 28(50.00) 24(53.34) Mild 23(22.77) 18(32.14) 5(11.11) Moderate 19(18.81) 8(14.29) 11(24.44) Severe 7(6.93) 2(3.57) 5(11.11) Undernutrition, n(%) 22(21.78) 11(19.64) 11(24.44) Wasting 14(13.86) 7(12.50) 7(15.56) NS Stunting 6(5.94) 2(3.57) 4(8.89) NS Underweight 10(9.90) 9(16.07) 1(2.22) 0.048 IBD therapy, n(%) NS Mesalazine 5(4.95) 2(3.57) 3(6.67) Oral/parenteral steroids 3(2.97) 3(5.36) 0 6MP 5(4.95) 4(7.14) 1(2.22) Biological therapy 61(60.40) 37(66.07) 24(53.33) Anti-TNF-α 60(59.41) 36(64.29) 24(53.33) Adalimumab 20(19.80) 15(26.79) 5(11.11) Infliximab 40(39.60) 21(37.50) 19(42.22) IL-12/23 inhibitor(Ustekinumab) 1(0.99) 1(1.79) 0 Thalidomide 6(5.94) 2(3.57) 4(8.89) Drug combination, n(%) 9(8.91) 6(10.71) 3(6.67) NS Exposure of COVID-19, n(%) 51(50.50) 36(64.29) 15(33.33) 0.002 *NS = no statistical significance Additional Declarations No competing interests reported. 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Chen","email":"","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pei-Yu","middleName":"","lastName":"Chen","suffix":""},{"id":260715462,"identity":"156c6f61-c22b-4abf-a81e-530e91ad2059","order_by":2,"name":"Hui-Wen Li","email":"","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hui-Wen","middleName":"","lastName":"Li","suffix":""},{"id":260715463,"identity":"a793e19d-db74-47f1-b189-5028091e3780","order_by":3,"name":"Lu Ren","email":"","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical 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Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li-Juan","middleName":"","lastName":"Wei","suffix":""},{"id":260715467,"identity":"1f2eaecf-6d86-490d-9608-e375e70f09cf","order_by":7,"name":"Zi-Huan Zeng","email":"","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zi-Huan","middleName":"","lastName":"Zeng","suffix":""},{"id":260715468,"identity":"4ac48495-c70a-4e14-9052-a48b55268db4","order_by":8,"name":"Wan-Fu Xu","email":"","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wan-Fu","middleName":"","lastName":"Xu","suffix":""},{"id":260715469,"identity":"837435dc-e74e-4abf-b23a-79fabbc00486","order_by":9,"name":"Si-Tang Gong","email":"","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Si-Tang","middleName":"","lastName":"Gong","suffix":""},{"id":260715470,"identity":"bfbc42b0-1321-46c5-b929-d9518254592a","order_by":10,"name":"Lan-Lan Geng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIiWNgGAWjYBACfmbGxgcfKiR4+NmbDzAwNoAFDfBqkWxvbjacccZGTrLnWAJxWgzOHG+T5mxLMza44WNAnBaGG4kN0oxthxNnzuD5/PLnjm2JDezN2yQYau7g1ME4I7HBuODc4cR+6d5tFpJnbic28Bwrk2A49gynFmaJxIbkGWVAW+ac3WZg2AbUIpFjJsHYcBinFjaglsM8bIcTN9zIeWaQCNIi/wa/Fh6eg43NPGDv5zA/OAi2hQe/Fgn2xmZGaCCbMTa23TZu40krtkg4hluL/WH25z+gUfn448+227L97Ic33vhQg1sLqr/AJIhIIEoDMPQ+EKlwFIyCUTAKRhgAAFenY6+wwqtJAAAAAElFTkSuQmCC","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Lan-Lan","middleName":"","lastName":"Geng","suffix":""}],"badges":[],"createdAt":"2023-12-17 03:14:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3765503/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3765503/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":48558437,"identity":"fa9d13c3-891a-4759-b547-69ff1b936996","added_by":"auto","created_at":"2023-12-20 19:38:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":24410,"visible":true,"origin":"","legend":"\u003cp\u003eFlow Diagram of the included patients\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3765503/v1/570127a33a06ac3ee4a878a6.png"},{"id":48558436,"identity":"bf00830d-61e0-4cb7-9610-1c5fc76d28b5","added_by":"auto","created_at":"2023-12-20 19:38:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":16639,"visible":true,"origin":"","legend":"\u003cp\u003eClinical characteristics of IBD children with SARS-CoV-2 infection.\u003c/p\u003e","description":"","filename":"F2.png","url":"https://assets-eu.researchsquare.com/files/rs-3765503/v1/72654134f13ef77dc4fdda74.png"},{"id":56506709,"identity":"62e74810-31b0-4dcc-ae0c-02abd240c9e5","added_by":"auto","created_at":"2024-05-15 05:38:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":568217,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3765503/v1/41eab688-8a83-4f60-85ee-29ec8957cf11.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The incidence and clinical characteristics of COVID-19 in children with IBD during the Omicron Wave: a single-center experience in China","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, is an acute infectious respiratory syndrome first reported in December 2019\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. It exponentially spread across all continents in just a few weeks and brought great challenges to global public health\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The World Health Organization has defined five variants of SARS-CoV-2 (VoC) of concern, named Alpha, Beta, Gamma, Delta, and Omicron. Since its identification in November 2021, the Omicron variant has spread rapidly around the globe and cause large outbreaks in children and adolescents\u003csup\u003e[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt has been reported that immunocompromised patients are at increased risk of severe illness and mortality from infection, and serious complications may occur in children, especially those with chronic and underlying conditions\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Characterized by immune-mediated chronic inflammation of the gastrointestinal tract, patients with inflammatory bowel disease (IBD) get increasing concern about the impact of COVID-19. Whether disease activity and biological treatment are risk factors for COVID-19 in IBD patients remains controversial\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. The actual risk of infection or development of COVID-19 in these at-risk patients with IBD is not clear, particularly in children and adolescents treated with immunosuppressants or biologics.\u003c/p\u003e \u003cp\u003eIn the past few years, China has responded by implementing non-pharmaceutical interventions (NPIs) with a series of public health and social measures, so called zero-COVID policy. After the announcement of \u0026ldquo;20 measures\u0026rdquo; in December 2022, the management of COVID-19 has been downgraded from Class A to Class B in accordance with the country's law on infectious diseases prevention and treatment, meaning the end of zero-COVID policy and the enterance to a new phase of the COVID-19 response\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. In this new phase of the pandemic, China is facing unprecedented challenges, so do the IBD children. With this in mind, we investigate the epidemiology, clinical characteristics, and outcomes of COVID-19 in PIBD patients. We conducted a cross-sectional study among the PIBD patients in our tertiary IBD center, in the first month following the transition of prevention policy, all IBD patients younger than 18 years old were included.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cp\u003e To evaluate the impact of COVID-19 on PIBD patients, after the approval of the ethics committee of the Guangzhou Women and Children's Medical Center, we conducted a retrospective cross-sectional study among PIBD patients followed in our center. All patients were individually contacted by online survey, phone, and face-to-face assessment between December 1st 2022 and January 31st 2023. Patients younger than 18 years old who were diagnosed as IBD were eligible for this study. The flow diagram of the included patients is demonstrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. An online survey was conducted in Chinese by the Questionnaire Star platform (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.wjx.cn\u003c/span\u003e\u003cspan address=\"https://www.wjx.cn\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The questionnaire was filled in by the child's parents/caregivers, and the information of clinical manifestation and follow-up assessments were reconfirmed by gastroenterologists at our institution. The COVID-19 cases were confirmed according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 9) and WHO public health surveillance for COVID-19, the symptoms and severity of SARS-CoV-2 infection in children were classified as asymptomatic, mild, moderate and severe. Undernutrition of PIBD patients was described as thinness (low BMI-for-age), stunting (low height-for-age) and underweight (low weight-for-age) according to the WHO definition.\u003c/p\u003e \u003cp\u003eThe survey documents the data on demographics, diseases and conditions (including diagnosis, disease activity, and treatment), and information about COVID-19. Disease activity was calculated at the time of the last available clinical follow-up using pediatric Crohn's disease (CD) and ulcerative colitis (UC) activity indexes. All patients were asked to describe if they experienced subjective worsening of IBD symptoms and details for hospitalized patients during COVID-19. COVID-19 outcomes were classified as outpatient care, hospitalization, ventilator requirement, and death from COVID-19 or related complications.\u003c/p\u003e \u003cp\u003e Written informed consent was obtained from the parents of the included children during the primary data collection process. All data used in this study were again to verify by gastroenterologists.\u003c/p\u003e"},{"header":"3. Statistical analysis","content":"\u003cp\u003eDescriptive statistics were calculated for the basic demographic and clinical characteristics of the study population. Continuous variables were summarized as means and standard deviations, and categorical variables as proportions. The differences between groups were compared using the Mann-Whitney U test, Kruskal-Wallis H test, and Student's t-test, as appropriate.\u003c/p\u003e \u003cp\u003eThe chi-square test or Fisher's exact test was used to examine the differences between groups when the cell numbers were less than five. All statistical analyses were performed using a statistical software package (SPSS-20). Two-sided \u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"4. Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e4.1 \u003cem\u003eDemographics and Characteristics of the IBD Children\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eA total of 101 questionnaires were analyzed, 56 of them test positive of SARS-CoV-2, which means the incidence of SARS-CoV-2 infection was 55.45%. Demographic, clinical characteristics of pediatric IBD patients with SARS-CoV-2 test are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of PIBD patients was 11.08 years (\u0026plusmn;\u0026thinsp;4.14). As expected, most patients were male (65.35%). It is the same in SARS-CoV-2 infected patients (67.86%). The difference of COVID-19 incidence between male and female pediatric IBD patients was no significant.\u003c/p\u003e \u003cp\u003ePatients with CD account for the majority of PIBD(91.09%), and most of IBD patients were in clinical remission(51.49%)\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Among the 56 IBD patients who tested positive for SARS-CoV-2, 52 were CD, 1 was UC, and 3 were unclassified colitis. According to the Paris classification, we classified age at diagnosis as 0 to \u0026lt;\u0026thinsp;10 years and 10 to \u0026lt;\u0026thinsp;17 years, the rate of SARS-CoV-2 infection was about the same between two groups. Of all patients, the mean duration of disease was 2.54 years, the longest was 10 years.\u003c/p\u003e \u003cp\u003eAs recorded in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the nutritional status of IBD children was divided into three subgroups based on the definition of WHO growth reference. Within the cohort, 14(13.86%) patients were wasting, 6(5.94%) patients were stunting, and 10(9.9%) patients were underweight. It's worth noting that 9 out of 10 patients who were underweight got SARS-CoV-2 infection, which showed a statistic difference on incidence of COVID-19 between PIBD patients with and without underweight(\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048).\u003c/p\u003e \u003cp\u003eOf the included children, 61 patients (60.40%) were on biological treatment, 5 were on mesalazine, 6 were on thiopurines and 3 were on steroids. Of the 61 patients on biological therapy, 40 were on infliximab, 20 were on adalimumab, and 1 was on ustekinumab. To be noticed, 9 patients were in combo-therapy (3 were on anti-TNF-α treatment together with thalidomide, 2 were on anti-TNF-αtreatment and thiopurines, 1 was on thalidomide and mesalazine, 1 was on anti-TNF-α treatment together with mesalazine, 1 was on steroids and mesalazine, 1 was on steroids and thiopurines). There were no significant differences in the incidence of COVID-19 between different treatments. 1 patient confirmed to have IL-10 receptor A (IL-10 RA) defect, 1 patient had comorbidity of immunodeficiency.\u003c/p\u003e \u003cp\u003e51 patients were reported to be in close contact with persons confirmed with COVID-19 infection, out of them, 70.59% patients test positive of SARS-CoV-2, which is significantly higher than it in patients without COVID-19 exposure (70.59% vs. 33.33%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e4.2 \u003cem\u003eClinical manifestation of SARS-CoV-2 infection in children with IBD\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eAmong the 56 IBD patients who tested positive for SARS-CoV-2, 53(94.64%) patients presented with mild symptoms, 3(5.36%) were asymptomatic. No one was classified with moderate and severe COVID-19, and no patient died. List of symptoms was summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The most common symptoms were fever (92.86%), mean duration was 1.84 days. The top five most common symptoms among symptomatic cases were fever(92.86%), cough(69.64%), rhinobyon and running nose(35.71%), sore throat (33.93%), and fatigue(26.79%). Because of the popularization of COVID-19 knowledge, 45 of our patients (80.36%) didn\u0026rsquo;t need medical consultation, 10(17.86%) patients need outpatient care, and only 1 (1.78%) mild COVID-19 patient was hospitalized for 3 days.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e4.3 \u003cem\u003eVaccination status and Worsen of IBD symptoms\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eAmong the 101 children IBD patients involved, 97 patients were eligible for COVID-19 vaccination (aged\u0026thinsp;\u0026ge;\u0026thinsp;3 years), 31(31.96%) were unvaccinated. A total of 66(68.04%) patients received at least one dose of vaccination. The incidence of SARS-CoV-2 infection on unvaccinated patients and vaccinated patients were 70.97% and 48.48%, which showed a higher incidence of SARS-CoV-2 infection in unvaccinated patients (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049).\u003c/p\u003e \u003cp\u003eIn our cohort, the incidence of SARS-CoV-2 infection didn\u0026rsquo;t show significant difference between different disease activities in IBD. Among the 101 patients with IBD included in our cohort, 32(14.6%) had spontaneously interrupted their therapy because infection of SARS-CoV-2, all of them treated with immunosuppressors and biologics. Finally, the incidence of SARS-CoV-2 infection was 55.45% in whole pediatric IBD population.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Discussion","content":"\u003cp\u003eData about the incidence and its disease course of COVID-19 among patients with IBD remain scarce, especially in children and adolescents. We conduct the the first population-based study of COVID-19 among pediatric IBD patients and the first cross-sectional study after the end of the zero-COVID policy in China.\u003c/p\u003e \u003cp\u003eA total of 101 IBD children were included, the majority of them had CD (91.09%), and there was a slight predominance of males. Almost half of our patients were in clinical remission (51.49%). 56 patients were found SARS-CoV-2 infection. The estimated incidence is 55.45%, which is much lower than that of the overall population in Guangzhou(༞85%) reported on the press conference on Jan 18\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Even so, the incidence is significantly higher than it in other reports\u003csup\u003e[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. In addition, 11 patients were defined as highly suspected of COVID-19, which of whom presented influenza-like symptoms and closely contacted with confirmed cases, but didn\u0026rsquo;t have SARS-COV-2 test. The incidence of SARS-CoV-2 infection might be underestimated because of the suboptimal sensitivity of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 and the difficulty of getting tested\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSome studies indicate a higher risk of COVID-19 and mortality in patients with IBD, while some had the opposite conclusion\u003csup\u003e[\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. In our cohort, the incidence of COVID-19 in IBD population is much lower than it in the general population \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e, and a relatively small proportion of patients requiring hospitalization. No patient got severe COVID-19, and no deaths have been observed.\u003c/p\u003e \u003cp\u003eThere are reports showed that the strength of the association between active IBD and adverse outcomes varied with age and was greatest in younger patients, the association between severe clinical disease activity and COVID-19 outcomes was seen in patients\u0026thinsp;\u0026le;\u0026thinsp;50 years\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. In this study, we did not observe an association between clinical disease activity and the severity or incidence of COVID-19. It can also be explained that Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eStudies show that young children under 5 years of age and patients with comorbidity have increased risk of getting COVID-19\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. However, in our study, 13 patients were younger than 5 years-old, the infection rate of SARS-CoV-2 was about the same as it in other age group. Of the 101 patients included, 60.40% were on biologic therapy, mostly were anti-TNF-α therapy. We didn\u0026rsquo;t observe a significant statistical difference in the incidence of COVID-19 in patients treated with or without biologic therapy. Patients treated with biologics had a favorable outcome, which is consistent with former reports\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. In this study population, no severe course of COVID-19 was observed, symptoms reported by all patients were mild (mostly fever and cough). In our observation, we did not identify any association between COVID-19 infection rates or risk of severe course and IBD-related treatment, which was consistent with previous reports\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Constanze reported TNF-inhibitors and ustekinumab show a protective role in preventing respiratory tract infections among older age (\u0026gt;\u0026thinsp;49 years)\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e, and Lev also reported that patients who received biologics had a significantly milder course of disease\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe most frequent symptom in our cohort is fever, followed by cough, nasal symptoms, and sore throat, which is in common with the study of De Souza\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. They described the clinical characteristics of 1124 cases of children with COVID-19, fever was the most prevalent symptom, followed by cough, nasal symptoms, diarrhea, nausea, vomiting, fatigue, and respiratory distress.\u003c/p\u003e \u003cp\u003eAmong the included patients, 22(21.78%) were undernutrition, 10 of them were underweight. Notably, 9 out of 10 underweight patients got SARS-CoV-2 infection. Reports showed that patients with higher nutrition risk have worse outcome\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. In a large multiethnic cohort study of adults hospitalized with COVID-19, they found that patients who were underweight and those with BMIs above the overweight range were more likely to be intubated or die\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. These studies showed the association between underweight and poor outcomes of COVID-19\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. As in our study, we observe a significant high rate of SARS-CoC-2 infection in underweight PIBD patient, but all of them did not get severe course of COVID-19. Future studies should be performed between the body mass and outcomes of COVID-19.\u003c/p\u003e \u003cp\u003eSeveral preliminary studies have found a reduced risk of hospitalisation and severe outcomes for omicron relative to the delta variant of SARS-CoV-2\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. By evaluating neutralizing antibody response in a comparator group of children, who were vaccinated with two doses or a single dose of mRNA vaccine, Juanjie Tang found that largest reduction (25.2-fold) of neutralization titers in vaccinated children was observed against the Omicron variant\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. However, importantly, all 8 of the 9 children who received two doses of mRNA vaccine still showed Pseudovirion neutralization assay (PsVNA) 50 titers (for a sample dilution that resulted in 50% virus neutralization)\u0026thinsp;\u0026gt;\u0026thinsp;1:20 against Omicron. Vaccine induced a much broader neutralizing antibody response against SARS-CoV-2 variants of concern (VOCs) in naive children compared with the natural immunity induced following SARS-CoV-2 infection. Studies showed that a moderate vaccine effectiveness after 2 doses of BNT162b2 or CoronaVac in children and adolescents, and third doses of either BNT162b2 or CoronaVac provide substantial additional protection against severe COVID-19\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eStudies have shown that COVID-19 vaccine effectiveness in IBD patients is comparable with that in non-IBD controls\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. But several researches showed that anti-TNF-α treatment have attenuated response to vaccination against COVID-19. A multicentre, prospective, case-control study in UK also indicated the prioritization of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF-α and JAK inhibitors\u003csup\u003e[\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e. These studies underscored the importance of vaccination.\u003c/p\u003e \u003cp\u003eA systematic review and meta-regression study showed that vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21.0 percentage points among people of all ages\u003csup\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e. In our study, 66 patients got vaccinated, only 7 patients got booster vaccination, and most of our patients got last vaccination for more than 6 months before the Omicron wave. Among the patients who were eligible for COVID-19 vaccination, a higher risk of SARS-CoV-2 infection was found in unvaccinated patients than it in vaccinated patients. This result shows that even over 6 months after vaccination, COVID-19 vaccine remained efficient against SARS-CoV-2 infection.\u003c/p\u003e \u003cp\u003eSome studies reported that a complication of gastrointestinal disease observed in children is multisystem inflammatory syndrome in children (MIS-C), which included abdominal pain, diarrhea, ongoing fever, cardiac dysfunction and multiple organ failure\u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. We observed 16 patients had gastrointestinal symptoms, no one had MIS-C. There were some studies suggest that this imbalance in immune homeostasis especially in patients with severe COVID-19 has been linked to gastrointestinal symptoms such as diarrhea\u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e. Various etiopathogenetic hypotheses have been advanced to explain the occurrence of diarrhea in COVID-19 patients, including loss in enterocyte absorption capability, microscopic mucosal inflammation damage, and an impaired function of ACE2, which leads to a downstream dysbiosis and metabolite imbalance\u003csup\u003e[\u003cspan additionalcitationids=\"CR42 CR43 CR44\" citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/sup\u003e. As for our patients, there was no apparent aggravation of diarrhea compare to general patients.\u003c/p\u003e \u003cp\u003eFormer research showed that patients who discontinued or delayed therapy with anti-TNF-α agents or other biologics had a higher rate of relapse\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/sup\u003e. In our cohort, none of our patients modified the current treatment regimen, while 42.57% delayed or withheld it because of the epidemic. The main reasons of delay were the infection of COVID-19.\u003c/p\u003e \u003cp\u003eIn this study, we performed the first population-based study of SARS-CoV-2 infection among pediatric IBD patients in China, furthermore, the first study after the end of the zero-COVID policy. Second, we included 101 pediatric IBD patients in our institution, the data records are detailed. Third, we observe a higher rate of SARS-CoV-2 infection in underweight pediatric IBD patients, and \u0026ge;\u0026thinsp;1 dose of vaccination against infection was efficient against SARS-CoV-2 infection.\u003c/p\u003e \u003cp\u003eNonetheless, some limitations must be taken into consideration. First, pediatric IBD cases were included only in our institute, the small sample size of our cohort of patients prevent us from drawing any final conclusions on the risk factors of COVID-19 severity in the pediatric IBD population. Second, during the COVID-19 outbreak after the end of NPIs, a great number of COVID-19 patients caused the overrun of hospital. The lack of testing might underestimate the incidence of SARS-CoV-2 infection in IBD patients somewhat. Third, there was none severe COVID-19 case in our cohort that prevent us to identify risk factors related to the IBD demographic and treatment.\u003c/p\u003e"},{"header":"6. Conclusions","content":"\u003cp\u003eIn conclusion, we first reported the results of clinical data and incidence of SARS-Cov-2 infection in Chinese PIBD patients. The incidence of COVID-19 infection in our IBD cohort was 55.45%, which is found to be lower than general population. All patients had mild to no symptoms. We also observed a higher rate of SARS-CoV-2 infection in underweight or unvaccinated PIBD patients, which highlights the importance of nutrition management and vaccination in IBD children and adolescents. Further, follow-up study is necessary to help us conduct better strategies for children with IBD.\u003c/p\u003e "},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by Guangzhou Medical Key Disciplines and Specialties(grand No.011006003) and Guangzhou Key Laboratory Bowel Disease(grand No.2023A03J0866).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eRui Li contributed to conception and design, acquisition of data, data analysis and interpretation, and drafting of the manuscript. Lan-Lan Geng contributed to conception and design, data analysis and interpretation. All authors critically revised the manuscript, and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAvailability of Data and Materials:\u003c/h2\u003e \u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHuang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 2020/2/15; 395(10223): 497\u0026ndash;506.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH, Pei YY, Yuan ML, Zhang YL, Dai FH, Liu Y, Wang QM, Zheng JJ, Xu L, Holmes EC, Zhang YZ. 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Clin Infect Dis 2022 2022/8/24; 75(1): e361\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, Wu C, Liu H, Liu D, Shao J, Peng X, Yang Y, Liu Z, Xiang Y, Zhang F, Silva RM, Pinkerton KE, Shen K, Xiao H, Xu S, Wong G. SARS-CoV-2 Infection in Children. New Engl J Med 2020 2020/4/23; 382(17): 1663\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurke KE, Kochar B, Allegretti JR, Winter RW, Lochhead P, Khalili H, Colizzo FP, Hamilton MJ, Chan WW, Ananthakrishnan AN. Immunosuppressive Therapy and Risk of COVID-19 Infection in Patients With Inflammatory Bowel Diseases. Inflamm Bowel Dis 2021 2021/1/19; 27(2): 155\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWaggershauser CH, Tillack-Schreiber C, Weyh P, Alt E, Siegmund T, Berchthold-Benchieb C, Szokodi D, Schnitzler F, Ochsenk\u0026uuml;hn T. 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Lancet 2022 2022/1/29; 399(10323): 437\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang J, Novak T, Hecker J, Grubbs G, Zahra FT, Bellusci L, Pourhashemi S, Chou J, Moffitt K, Halasa NB, Schwartz SP, Walker TC, Tarquinio KM, Zinter MS, Staat MA, Gertz SJ, Cvijanovich NZ, Schuster JE, Loftis LL, Coates BM, Mack EH, Irby K, Fitzgerald JC, Rowan CM, Kong M, Flori HR, Maddux AB, Shein SL, Crandall H, Hume JR, Hobbs CV, Tremoulet AH, Shimizu C, Burns JC, Chen SR, Moon HK, Lange C, Randolph AG, Khurana S. Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C. Nat Commun 2022 2022/5/27; 13(1): 2979.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeung D, Rosa DJ, Yip KM, So HK, Wong W, Lau YL. Effectiveness of BNT162b2 and CoronaVac in children and adolescents against SARS-CoV-2 infection during Omicron BA.2 wave in Hong Kong. Commun Med (Lond) 2023 2023/1/5; 3(1): 3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcMenamin ME, Nealon J, Lin Y, Wong JY, Cheung JK, Lau E, Wu P, Leung GM, Cowling BJ. Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study. Lancet Infect Dis 2022 2022/10/1; 22(10): 1435\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLev-Tzion R, Focht G, Lujan R, Mendelovici A, Friss C, Greenfeld S, Kariv R, Ben-Tov A, Matz E, Nevo D, Barak-Corren Y, Dotan I, Turner D. COVID-19 Vaccine Is Effective in Inflammatory Bowel Disease Patients and Is Not Associated With Disease Exacerbation. Clin Gastroenterol H 2022 2022/6/1; 20(6): e1263\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBordalo FF, Rafael MA, Coimbra L, Boavida N, Arrobas F, Pereira CF, Martins FL, Carvalho EBJ, Carvalho LL, Santos L, Oliveira AM. 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Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet 2022 2022/3/5; 399(10328): 924\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr 2021 2021/7/1; 180(7): 2019\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, Han C, Zhang S, Duan C, Shang H, Bai T, Hou X. Diarrhea and altered inflammatory cytokine pattern in severe coronavirus disease 2019: Impact on disease course and in-hospital mortality. J Gastroen Hepatol 2021 2021/2/1; 36(2): 421\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu J, Han B, Wang J. COVID-19: Gastrointestinal Manifestations and Potential Fecal-Oral Transmission. Gastroenterology 2020 2020/5/1; 158(6): 1518\u0026ndash;1519.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHikmet F, M\u0026eacute;ar L, Edvinsson \u0026Aring;, Micke P, Uhl\u0026eacute;n M, Lindskog C. The protein expression profile of ACE2 in human tissues. Mol Syst Biol 2020 2020/7/1; 16(7): e9610.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSenapati S, Banerjee P, Bhagavatula S, Kushwaha PP, Kumar S. Contributions of human ACE2 and TMPRSS2 in determining host-pathogen interaction of COVID-19. J Genet 2021 2021/1/20; 100(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScaldaferri F, Ianiro G, Privitera G, Lopetuso LR, Vetrone LM, Petito V, Pugliese D, Neri M, Cammarota G, Ringel Y, Costamagna G, Gasbarrini A, Boskoski I, Armuzzi A. The Thrilling Journey of SARS-CoV-2 into the Intestine: From Pathogenesis to Future Clinical Implications. Inflamm Bowel Dis 2020 2020/8/20; 26(9): 1306\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, Sigl V, Hanada T, Hanada R, Lipinski S, Wild B, Camargo SM, Singer D, Richter A, Kuba K, Fukamizu A, Schreiber S, Clevers H, Verrey F, Rosenstiel P, Penninger JM. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nat 2012 2012/7/25; 487(7408): 477\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurner D, Huang Y, Mart\u0026iacute;n-de-Carpi J, Aloi M, Focht G, Kang B, Zhou Y, Sanchez C, Kappelman MD, Uhlig HH, Pujol-Muncunill G, Ledder O, Lionetti P, Dias JA, Ruemmele FM, Russell RK. Corona Virus Disease 2019 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastr Nutr 2020 2020/6/1; 70(6): 727\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":" \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics and clinical characteristics of pediatric IBD population.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eSARS-CoV-2 TEST\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALL\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;101)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;56)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;45)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66(65.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38(67.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e28(62.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, year (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.08(\u0026plusmn;4.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.15(\u0026plusmn;3.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e10.96(\u0026plusmn;4.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIBD classification, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCD\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92(91.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52(92.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e40(55.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUC\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3(6.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUnclassified\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(4.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(5.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2(4.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at the time of IBD diagnosis, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e༜10y\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50(49.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e22(48.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e10-17y\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51(50.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e23(51.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIBD disease activity, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRemission\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52(51.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e24(53.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMild\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(22.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(32.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eModerate\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(18.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e11(24.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSevere\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(6.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndernutrition, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22(21.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(19.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e11(24.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWasting\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(13.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(12.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e7(15.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStunting\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(5.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e4(8.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUnderweight\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(9.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(16.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1(2.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.048\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIBD therapy, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMesalazine\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(4.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3(6.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eOral/parenteral steroids\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(2.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(5.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e6MP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(4.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(7.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1(2.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBiological therapy\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61(60.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37(66.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e24(53.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAnti-TNF-α\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60(59.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(64.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e24(53.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAdalimumab\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(19.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(26.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eInfliximab\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40(39.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(37.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e19(42.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIL-12/23 inhibitor(Ustekinumab)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eThalidomide\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(5.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e4(8.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug combination, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(8.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3(6.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExposure of COVID-19, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51(50.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(64.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e15(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c7\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e*NS\u0026thinsp;=\u0026thinsp;no statistical significance\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, inflammatory bowel disease, pediatric, incidence, disease course, risk factors, cross-sectional study","lastPublishedDoi":"10.21203/rs.3.rs-3765503/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3765503/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eThe pandemic of Coronavirus disease 2019 (COVID-19) had a major impact on the health of people worldwide, including the pediatric inflammatory bowel diseases (PIBD) patients. As no study has investigated the susceptibility and disease course of COVID-19 in PIBD patients after the end of zero-COVID policy in China, we conducted a retrospective cross-sectional study in our center.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA cross-sectional survey enrolling PIBD patients has been completed by online survey, phone, and face-to-face assessment. The demographic data, epidemiological characteristics, clinical manifestations, treatment and prognosis of the patients were analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePIBD patients represented 55.45%(56/101) of SARS-CoV-2 positive cases between December 1st 2022 and January 31th 2023, 67.86% were male, mean age was 11.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.92 years old. Among the SARS-CoV-2 positive cases, 3 patients (5.36%) were asymptomatic, 53 patients (94.64%) had mild symptoms. The main symptoms were fever (92.86%), cough (69.64%), nasal congestion or runnig nose (35.71%), and sore throat (33.93%). No severe case or deaths were reported. All patients recovered from COVID-19 symptoms within one week. We did not observe an association between different clinical disease activities and SARS-CoV-2 infection rates, so as it in different treatments. 51 patients were reported to be in close contact with persons confirmed with COVID-19 infection, and out of them, 36 patients test positive of SARS-CoV-2, which is significantly higher than it in patients without exposure of COVID-19 (70.59% vs. 33.33%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). A total of 10 patients were underweight, of which 9 patients tested positive for COVID-19(\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048). Meanwhile, unvaccinated patients were also found to be more susceptible to SARS-CoV-2 than vaccinated patients(70.97% vs. 48.48%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe incidence of SARS-CoV-2 infection in our center of pediatric IBD patients during the Omicron pandemic was 55.45%. No severity or death case was observed. Patients with underweight, unvaccinated and history of exposure to COVID-19 were at higher risk of SARS-CoV-2 infection.\u003c/p\u003e","manuscriptTitle":"The incidence and clinical characteristics of COVID-19 in children with IBD during the Omicron Wave: a single-center experience in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-12-20 19:38:39","doi":"10.21203/rs.3.rs-3765503/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f25bed5b-37e4-42ae-b7aa-dec95fa343f1","owner":[],"postedDate":"December 20th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-15T05:30:49+00:00","versionOfRecord":[],"versionCreatedAt":"2023-12-20 19:38:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3765503","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3765503","identity":"rs-3765503","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}