{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:10:20Z","timestamp":1784661020314,"version":"3.55.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammatory bowel disease (IBD) including Crohn\u2019s disease (CD) and ulcerative colitis (UC), are associated with higher thrombotic risk and enhanced thrombin generation (TG) in adults. Despite encouraging data reporting vaccine safety and low IBD flare rates in adults with IBD, vaccine hesitancy was demonstrated to be high in families of children with IBD. We aimed to find out whether TG is increased in children with IBD as compared to healthy controls and whether TG parameters show significant changes following SARS-CoV-2 mRNA vaccination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>In this observational case-control study, 38 children with IBD (CD:18, UC: 20) aged 12-18 years and 62 healthy age-and sex-matched children were enrolled. Blood was collected before the first dose and 2-6 weeks after the second dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine dose. Blood cell counts, fibrinogen, inflammatory markers (hsCRP, ferritin), anti-SARS-CoV-2 antibody levels were investigated, TG assay was carried-out using platelet-poor plasma. Detailed clinical parameters including disease activity scores (PUCAI, PCDAI) were registered pre-and post- vaccination. A guided questionnaire was used to collect data on adverse reactions (AEs) post- vaccination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Baseline TG parameters did not differ between patients and controls. Endogenous thrombin potential showed a significant positive correlation with markers of inflammation and with PCDAI. Inflammatory parameters and TG did not increase in patients and controls post-vaccination. Vaccination significantly increased antibody levels in all three investigated groups, but post-vaccination anti-SARS-CoV-2 S IgG\/IgM levels were below the 5<jats:sup>th<\/jats:sup> percentile value of healthy children in more than one third of patients. Those receiving TNF\u03b1 inhibitor therapy presented significantly lower SARS-CoV-2 S IgG\/IgM levels as compared to patients on other immunosuppressive regimens. Systemic AEs did not differ between patients and controls while lower rate of local symptoms was found post-vaccination in children with IBD. Only 2 IBD flares were detected 2-6 weeks after the second dose of vaccination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study is the first to support the safety and efficacy of anti-SARS-CoV-2 BNT162b2 vaccination in children with IBD with detailed pre-and post-vaccination laboratory data including TG. Results of this study may further increase confidence and reduce vaccine hesitancy in caretakers of pediatric IBD patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1257072","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T10:41:03Z","timestamp":1698662463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of anti-SARS-CoV-2 BNT162b2 mRNA vaccination on thrombin generation in children with inflammatory bowel disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Vivien","family":"Stercel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"L\u00f3czi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsolya","family":"Kadenczki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Nemes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"B\u00e9la","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeka","family":"Hodossy-Tak\u00e1cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila \u00c1d\u00e1m","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Fagyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Kappelmayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsa","family":"Bagoly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.disamonth.2017.07.001","article-title":"A comprehensive review and update on Crohn's disease","volume":"64","author":"Gajendran","year":"2018","journal-title":"Dis Mon"},{"key":"B2","doi-asserted-by":"publisher","first-page":"100851","DOI":"10.1016\/j.disamonth.2019.02.004","article-title":"A comprehensive review and update on ulcerative colitis","volume":"65","author":"Gajendran","year":"2019","journal-title":"Dis Mon"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.2017.0331","article-title":"Inflammatory bowel disease in childhood and adolescence","volume":"114","author":"Dabritz","year":"2017","journal-title":"Dtsch Arztebl Int"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00492-8","article-title":"International consensus on the prevention of venous and arterial thrombotic events in patients with inflammatory bowel disease","volume":"18","author":"Olivera","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2009.10.012","article-title":"Increased thrombin generation in inflammatory bowel diseases","volume":"125","author":"Saibeni","year":"2010","journal-title":"Thromb Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21631","article-title":"Thrombin generation in pediatric patients with Crohn's disease","volume":"17","author":"Bernhard","year":"2011","journal-title":"Inflamm Bowel Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e31827daf72","article-title":"Increased procoagulant function of microparticles in pediatric inflammatory bowel disease: role in increased thrombin generation","volume":"56","author":"Deutschmann","year":"2013","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00878-2","article-title":"The evolution of SARS-coV-2","volume":"21","author":"Markov","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11092676","article-title":"COVID-19 vaccination in inflammatory bowel disease (IBD)","volume":"11","author":"Kubas","year":"2022","journal-title":"J Clin Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otaa056","article-title":"Vaccination rates and family barriers among children with inflammatory bowel disease","volume":"2","author":"Holland","year":"2020","journal-title":"Crohns Colitis 360"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab302","article-title":"Impact of SARS-coV-2 vaccination on inflammatory bowel disease activity and development of vaccine-related adverse events: Results from PREVENT-COVID","volume":"28","author":"Weaver","year":"2022","journal-title":"Inflamm Bowel Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11030641","article-title":"Real-world use and adverse events of SARS-coV-2 vaccination in greek patients with inflammatory bowel disease","volume":"11","author":"Orfanoudaki","year":"2022","journal-title":"J Clin Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"100970","DOI":"10.1016\/j.blre.2022.100970","article-title":"No apparent association between mRNA COVID-19 vaccination and venous thromboembolism","volume":"56","author":"Nicholson","year":"2022","journal-title":"Blood Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2014.04.005","article-title":"Consensus guidelines of ECCO\/ESPGHAN on the medical management of pediatric Crohn's disease","volume":"8","author":"Ruemmele","year":"2014","journal-title":"J Crohns Colitis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-199105000-00005","article-title":"Development and validation of a pediatric Crohn's disease activity index","volume":"12","author":"Hyams","year":"1991","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.05.029","article-title":"Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study","volume":"133","author":"Turner","year":"2007","journal-title":"Gastroenterology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.785744","article-title":"Angiotensin converting enzyme activity in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients","volume":"8","author":"Soos","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.912664","article-title":"Thrombin generation as a predictor of outcomes in patients with non-traumatic intracerebral hemorrhage","volume":"13","author":"Loczi","year":"2022","journal-title":"Front Neurol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1111\/apa.16652","article-title":"The safety of COVID-19 vaccination in immunocompromised children and young adults with immune-mediated inflammatory disease","volume":"112","author":"Sahn","year":"2023","journal-title":"Acta Paediatr"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000003661","article-title":"Postvaccination immunogenicity of BNT162b2 SARS-coV-2 vaccine and its predictors in pediatric inflammatory bowel disease","volume":"76","author":"Bronsky","year":"2023","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000002016","article-title":"Humoral immune response and safety of SARS-coV-2 vaccination in pediatric inflammatory bowel disease","volume":"118","author":"Kastl","year":"2023","journal-title":"Am J Gastroenterol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10071109","article-title":"Evaluation of safety and immunogenicity of BNT162B2 mRNA COVID-19 vaccine in IBD pediatric population with distinct immune suppressive regimens","volume":"10","author":"Cotugno","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10101618","article-title":"Impact of anti-TNFalpha treatment on the humoral response to the BNT162b2 mRNA COVID-19 vaccine in pediatric inflammatory bowel disease patients","volume":"10","author":"Kashiwagi","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjab147","article-title":"T cell response after SARS-coV-2 vaccination in immunocompromised patients with inflammatory bowel disease","volume":"16","author":"Reuken","year":"2022","journal-title":"J Crohns Colitis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1016\/j.cgh.2022.01.056","article-title":"Strong response to SARS-coV-2 vaccine additional doses among patients with inflammatory bowel diseases","volume":"20","author":"Long","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322449","article-title":"Adaptations to the current ECCO\/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: A RAND appropriateness panel","volume":"70","author":"Hansen","year":"2021","journal-title":"Gut"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12666","article-title":"COVID-19 and venous thromboembolism: A narrative review","volume":"6","author":"Angelini","year":"2022","journal-title":"Res Pract Thromb Haemost"},{"key":"B28","article-title":"Immunizations in children with inflammatory bowel disease treated with immunosuppressive therapy","volume":"10","author":"Lu","year":"2014","journal-title":"Gastroenterol Hepatol (N Y)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1257072\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T10:41:05Z","timestamp":1698662465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1257072\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,30]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2023.1257072"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1257072","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,30]]},"article-number":"1257072"}}