Postvaccination Immunogenicity of BNT162b2 SARS-CoV-2 Vaccine and Its Predictors in Pediatric Inflammatory Bowel Disease

Objectives: We prospectively compared the postvaccination immunity to messenger ribonucleic acid BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine of our pediatric patients over 12 years old with inflammatory bowel disease (IBD) to that of healthy controls and looked for predictors of its robustness. Methods: Anti-receptor binding domain, anti-spike S2, and anti-nucleocapsid immunoglobin-G (IgG) and immunoglobin-A levels were measured in 139 pediatric patients with IBD [65 fully vaccinated (2 doses), median age 16.3, interquartile range (IQR) 15.2–17.8 years, median time from vaccination (IQR) 61.0 (42.0–80.0) days] and 1744 controls (46, 37–57 years) using microblot array. Results: All IBD and control patients developed positive anti-receptor binding domain IgG antibodies at comparable titers. The proportion of observations with positive anti-spike S2 IgG was higher in patients with IBD than in controls [63% vs 21%, odds ratio 2.99 (1.51–5.90)], as was its titer [median (IQR) 485 (92–922) vs 79 [33–180] IU/mL]. Anti-receptor binding domain and anti-spike S2 IgG levels were associated with IBD status. We found an association between anti-spike S2 IgG levels and time since vaccination (β −4.85, 95% CI −7.14 to 2.71, P = 0.0001), history of SARS-CoV-2 polymerase chain reaction positivity (206.76, 95% CI 39.93–374.05, P = 0.0213), and anti-tumor necrosis factor treatment (−239.68, 95% CI −396.44–83.55, P = 0.0047). Forty-three percent of patients reported vaccination side effects (mostly mild). Forty-six percent of observations with positive anti-nucleocapsid IgG had a history of SARS-CoV-2 infection. Conclusions: Patients with IBD produced higher levels of postvaccination anti-spike S2 antibodies than controls. Previous SARS-CoV-2 infection is associated with higher production of postvaccination antibodies and anti-tumor necrosis factor treatment with lower production.

[1]  Susan M. Kilroy,et al.  Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab , 2022, Nature Communications.

[2]  S. Sebastian,et al.  Effectiveness and Durability of COVID-19 Vaccination in 9447 Patients With IBD: A Systematic Review and Meta-Analysis , 2022, Clinical Gastroenterology and Hepatology.

[3]  P. Higgins,et al.  Strong Response to SARS-CoV-2 Vaccine Additional Doses Among Patients With Inflammatory Bowel Diseases , 2022, Clinical Gastroenterology and Hepatology.

[4]  L. Targownik,et al.  Is the attenuated humoral response to COVID-19 vaccination in anti-TNF users relevant? , 2022, The Lancet Gastroenterology & Hepatology.

[5]  M. Parkes,et al.  COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study , 2022, The Lancet Gastroenterology & Hepatology.

[6]  D. Segev,et al.  Antibody Response 3 Months After 2-Dose SARS-CoV-2 mRNA Vaccination in Patients With Inflammatory Bowel Disease , 2022, The American journal of gastroenterology.

[7]  H. Mulcahy,et al.  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) , 2022, Journal of Crohn's & colitis.

[8]  E. Lorentzen,et al.  Humoral Immune Response in IBD Patients Three and Six Months after Vaccination with the SARS-CoV-2 mRNA Vaccines mRNA-1273 and BNT162b2 , 2022, Biomedicines.

[9]  D. Segev,et al.  Antibody Response Six Months after SARS-CoV-2 mRNA Vaccination in Patients with Inflammatory Bowel Disease , 2022, Clinical Gastroenterology and Hepatology.

[10]  OUP accepted manuscript , 2022, Journal of Crohn’s and Colitis.

[11]  M. Dubinsky,et al.  Factors Affecting Initial Humoral Immune Response to SARS-CoV-2 Vaccines Among Patients With Inflammatory Bowel Diseases , 2021, The American journal of gastroenterology.

[12]  Yen‐Po Wang,et al.  SARS-CoV-2 vaccination in patients with inflammatory bowel disease: A systemic review and meta-analysis , 2021, Journal of the Chinese Medical Association : JCMA.

[13]  H. Messmann,et al.  Antibody Response to SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Disease: Results of a Single-Center Cohort Study in a Tertiary Hospital in Germany , 2021, Digestive Diseases.

[14]  D. McGovern,et al.  The T-cell clonal response to SARS-CoV-2 vaccination in inflammatory bowel disease patients is augmented by anti-TNF therapy and often deficient in antibody-responders , 2021, medRxiv.

[15]  D. McGovern,et al.  Post-Vaccination Symptoms after A Third Dose of mRNA SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Disease , 2021, medRxiv.

[16]  M. Dubinsky,et al.  Impact of SARS-CoV-2 Vaccination on Inflammatory Bowel Disease Activity and Development of Vaccine-Related Adverse Events: Results From PREVENT-COVID , 2021, Inflammatory bowel diseases.

[17]  I. Dotan,et al.  COVID-19 Vaccine Is Effective in Inflammatory Bowel Disease Patients and Is Not Associated With Disease Exacerbation , 2021, Clinical Gastroenterology and Hepatology.

[18]  R. Longman,et al.  Impact of Inflammatory Bowel Disease Therapies on Durability of Humoral Response to SARS-CoV-2 Vaccination , 2021, Clinical Gastroenterology and Hepatology.

[19]  M. Lukáš,et al.  Anti-SARS-CoV-2 Vaccination and Antibody Response in Patients With Inflammatory Bowel Disease on Immune-modifying Therapy: Prospective Single-Tertiary Study. , 2021, Inflammatory bowel diseases.

[20]  S. Carmagnola,et al.  Risk of adverse events and reported clinical relapse after COVID-19 vaccination in patients with IBD , 2021, Gut.

[21]  S. Saha,et al.  Humoral Immunogenicity of mRNA COVID-19 Vaccines Among Patients With Inflammatory Bowel Disease and Healthy Controls , 2021, The American journal of gastroenterology.

[22]  M. Abu-Farha,et al.  Immunogenicity of BNT162b2 Vaccine in Patients with Inflammatory Bowel Disease on Infliximab Combination Therapy: A Multicenter Prospective Study , 2021, medRxiv.

[23]  N. Freund,et al.  Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα , 2021, Gastroenterology.

[24]  D. Unutmaz,et al.  Antibody Responses to SARS-CoV-2 After Infection or Vaccination in Children and Young Adults With Inflammatory Bowel Disease , 2021, Inflammatory bowel diseases.

[25]  E. Torres,et al.  Early immunologic response to mRNA COVID-19 vaccine in patients receiving biologics and/or immunomodulators , 2021, medRxiv.

[26]  Philip Smith,et al.  Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients , 2021, Journal of Crohn's & colitis.

[27]  S. Fennessy,et al.  Review Article: vaccination for patients with inflammatory bowel disease during the COVID‐19 pandemic , 2021, Alimentary pharmacology & therapeutics.

[28]  T. Kamradt,et al.  T cell response after SARS-CoV-2 vaccination in immunocompromised patients with inflammatory bowel disease , 2021, Journal of Crohn's & colitis.

[29]  J. Bronský,et al.  SARS-CoV-2 Vaccination for Paediatric Patients with Inflammatory Bowel Diseases. , 2021, Journal of pediatric gastroenterology and nutrition.

[30]  N. Kennedy,et al.  Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis , 2021, Autoimmunity Reviews.

[31]  S. Targan,et al.  Decreased Antibody Responses to Ad26.COV2.S Relative to SARS-CoV-2 mRNA Vaccines in Patients With Inflammatory Bowel Disease , 2021, Gastroenterology.

[32]  S. Connor,et al.  SARS‐CoV‐2 vaccination in patients with inflammatory bowel disease , 2021, GastroHep.

[33]  P. Dormitzer,et al.  Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents , 2021, The New England journal of medicine.

[34]  D. McGovern,et al.  Adverse Events After SARS-CoV-2 mRNA Vaccination Among Patients With Inflammatory Bowel Disease , 2021, The American journal of gastroenterology.

[35]  N. Mahmud,et al.  Effectiveness of SARS-CoV-2 Vaccination in a Veterans Affairs Cohort of Patients With Inflammatory Bowel Disease With Diverse Exposure to Immunosuppressive Medications , 2021, Gastroenterology.

[36]  M. Dubinsky,et al.  Seroconversion Following SARS-CoV-2 Infection or Vaccination in Pediatric IBD Patients , 2021, medRxiv.

[37]  S. Ng,et al.  Serologic Response to Messenger RNA Coronavirus Disease 2019 Vaccines in Inflammatory Bowel Disease Patients Receiving Biologic Therapies , 2021, Gastroenterology.

[38]  S. Ng,et al.  Serologic Response to Messenger RNA Coronavirus Disease 2019 Vaccines in Inflammatory Bowel Disease Patients Receiving Biologic Therapies , 2021, Gastroenterology.

[39]  C. Lees,et al.  Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD , 2021, Gut.

[40]  J. Satsangi,et al.  SARS-CoV-2 vaccination in IBD: past lessons, current evidence and future challenges , 2021, Journal of Crohn's & colitis.

[41]  C. Lees,et al.  Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab , 2021, Gut.

[42]  M. Parkes,et al.  SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement , 2021, The Lancet Gastroenterology & Hepatology.

[43]  M. Dubinsky,et al.  SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting , 2021, Gut.

[44]  OUP accepted manuscript , 2021, Journal of the Canadian Association of Gastroenterology.

[45]  A. Griffiths,et al.  Mathematical weighting of the pediatric Crohn's disease activity index (PCDAI) and comparison with its other short versions , 2012, Inflammatory bowel diseases.

[46]  A. Griffiths,et al.  Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. , 2007, Gastroenterology.