Effect of anti-SARS-CoV-2 BNT162b2 mRNA vaccination on thrombin generation in children with inflammatory bowel disease

Front Immunol. 2023 Oct 30:14:1257072. doi: 10.3389/fimmu.2023.1257072. eCollection 2023.

Abstract

Background: Inflammatory bowel disease (IBD) including Crohn's 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.

Patients and methods: 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.

Results: 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 5th percentile value of healthy children in more than one third of patients. Those receiving TNFα 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.

Conclusion: 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.

Keywords: COVID-19; Crohn’s disease; inflammatory bowel disease; severe acute respiratory syndrome coronavirus-2; thrombin generation; ulcerative colitis.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • BNT162 Vaccine
  • COVID-19* / prevention & control
  • Case-Control Studies
  • Child
  • Colitis, Ulcerative*
  • Crohn Disease*
  • Humans
  • Immunoglobulin G
  • Immunoglobulin M
  • Inflammatory Bowel Diseases*
  • RNA, Messenger
  • SARS-CoV-2
  • Thrombin

Substances

  • Antibodies, Viral
  • BNT162 Vaccine
  • Immunoglobulin G
  • Immunoglobulin M
  • RNA, Messenger
  • Thrombin

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Supported by grants from the National Research, Development and Innovation Fund (NKFI FK128582, K147243, K129287) and TKP 2021 EGA-19, financed under the TKP2021-EGA funding scheme, by ÚNKP 22-3-II-DE-167, ÚNKP 23-5-DE-482 and POST-COVID2021-33 grants. MF was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00069/21/5).