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.

From the Department of Paediatrics 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

the Clinical and Research Centre for Inflammatory Bowel Disease ISCARE and 1st Faculty of Medicine Charles University Prague Czech Republic

the Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

J Pediatr Gastroenterol Nutr. 2023 Jun 1;76(6):e90. doi: 10.1097/MPG.0000000000003760. PubMed

J Pediatr Gastroenterol Nutr. 2023 Jun 1;76(6):e89-e90. doi: 10.1097/MPG.0000000000003761. PubMed

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Alexander JL, Moran GW, Gaya DR, 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. Lancet Gastroenterol Hepatol. 2021;6:218–24. PubMed PMC

Murthy SK, Kuenzig ME, Windsor JW, et al. . Crohn’s and Colitis Canada’s 2021 impact of COVID-19 and inflammatory bowel disease in Canada: COVID-19 vaccines-biology, current evidence and recommendations. J Can Assoc Gastroenterol. 2021;4:S54–60. PubMed PMC

Siegel CA, Melmed GY, McGovern DP, et al. . SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting. Gut. 2021;70:635–40. PubMed PMC

Frenck RW, Jr, Klein NP, Kitchin N, et al. . Safety, immunogenicity, and efficacy of the BNT162b2 covid-19 vaccine in adolescents. N Engl J Med. 2021;385:239–50. PubMed PMC

Veereman G, Bronsky J. Severe acute respiratory syndrome coronavirus 2 vaccination for paediatric patients with inflammatory bowel diseases. J Pediatr Gastroenterol Nutr. 2021;73:433–6. PubMed

Dailey J, Kozhaya L, Dogan M, et al. . Antibody responses to SARS-CoV-2 after infection or vaccination in children and young adults with inflammatory bowel disease. Inflamm Bowel Dis. 2022;28:1019–1026. PubMed PMC

Kappelman MD, Weaver KN, Zhang X, et al. . Factors affecting initial humoral immune response to SARS-Cov-2 vaccines among patients with inflammatory bowel diseases. Am J Gastroenterol. 2022;117:462–9. PubMed

Spencer EA, Klang E, Dolinger M, Pittman N, Dubinsky MC. Seroconversion following SARS-CoV-2 infection or vaccination in pediatric IBD patients. Inflamm Bowel Dis. 2021;27:1862–4. PubMed PMC

Turner D, Griffiths AM, Walters TD, et al. . Mathematical weighting of the pediatric Crohn’s disease activity index (PCDAI) and comparison with its other short versions. Inflamm Bowel Dis. 2012;18:55–62. PubMed

Turner D, Otley AR, Mack D, et al. . Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. 2007;133:423–32. PubMed

Jena A, James D, Singh AK, Dutta U, Sebastian S, Sharma V. Effectiveness and durability of COVID-19 vaccination in 9447 patients with IBD: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2022;20:1456–79.e18. PubMed PMC

Jena A, Mishra S, Deepak P, et al. . Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: systematic review and meta-analysis. Autoimmun Rev. 2022;21:102927. PubMed PMC

Sung KY, Chang TE, Wang YP, et al. . SARS-CoV-2 vaccination in patients with inflammatory bowel disease: systemic review and meta-analysis. J Chin Med Assoc. 2022;85:421–30. PubMed

Pozdnyakova V, Botwin GJ, Sobhani K, et al. . Decreased antibody responses to Ad26.COV2.S relative to SARS-CoV-2 mRNA vaccines in patients with inflammatory bowel disease. Gastroenterology. 2021;161:2041–3.e1. PubMed PMC

Doherty J, Fennessy S, Stack R, et al. . Review article: vaccination for patients with inflammatory bowel disease during the COVID-19 pandemic. Aliment Pharmacol Ther. 2021;54:1110–23. PubMed PMC

Doherty J, N OM, Stack R, 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). J Crohns Colitis. 2022;16:1354–62. PubMed PMC

Rodriguez-Martino E, Medina-Prieto R, Santana-Bagur J, et al. . Early immunologic response to mRNA COVID-19 vaccine in patients receiving biologics and/or immunomodulators. medRxiv. 2021; 2021.09.11.21263211. doi:10.1101/2021.09.11.21263211.

Alexander JL, Kennedy NA, Ibraheim H, et al. . COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study. Lancet Gastroenterol Hepatol. 2022;7:342–52. PubMed PMC

Caldera F, Knutson KL, Saha S, et al. . Humoral immunogenicity of mRNA COVID-19 vaccines among patients with inflammatory bowel disease and healthy controls. Am J Gastroenterol. 2022;117:176–9. PubMed

Cerna K, Duricova D, Lukas M, et al. . Anti-SARS-CoV-2 vaccination and antibody response in patients with inflammatory bowel disease on immune-modifying therapy: prospective single-tertiary study. Inflamm Bowel Dis. 2022;28:1506–12. PubMed

Edelman-Klapper H, Zittan E, Bar-Gil Shitrit A, et al. . Lower serologic response to COVID-19 mRNA vaccine in patients with inflammatory bowel diseases treated with anti-TNFalpha. Gastroenterology. 2022;162:454–67. PubMed PMC

Frey S, Chowdhury R, Connolly CM, et al. . Antibody response six months after SARS-CoV-2 mRNA vaccination in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2022;20:1609–1612.e1. PubMed PMC

Charilaou P, Tricarico C, Battat R, Scherl EJ, Longman RS, Lukin DJ. Impact of inflammatory bowel disease therapies on durability of humoral response to SARS-CoV-2 vaccination. Clin Gastroenterol Hepatol. 2022;20:e1493–9. PubMed PMC

Kennedy NA, Lin S, Goodhand JR, et al. . Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD. Gut. 2021;70:1884–93. PubMed

Long MD, Weaver KN, Zhang X, Chun K, Kappelman MD. Strong response to SARS-CoV-2 vaccine additional doses among patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2022;20:1881–1883.e1. PubMed PMC

Prentice RE, Rentsch C, Al-Ani AH, et al. . SARS-CoV-2 vaccination in patients with inflammatory bowel disease. GastroHep. 2021;3:212–28. PubMed PMC

Shehab M, Abu-Farha M, Alrashed F, et al. . Immunogenicity of BNT162b2 vaccine in patients with inflammatory bowel disease on infliximab combination therapy: a multicenter prospective study. J Clin Med. 2021;10:5362. PubMed PMC

Tsipotis E, Frey S, Connolly C, et al. . Antibody response three months after two-dose SARS-CoV-2 mRNA vaccination in patients with inflammatory bowel disease. Am J Gastroenterol. 2022;117:798–801. PubMed

Vollenberg R, Tepasse PR, Kuhn JE, 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. Biomedicines. 2022;10:171. PubMed PMC

Wong SY, Dixon R, Martinez Pazos V, et al. . Serologic response to messenger RNA coronavirus disease 2019 vaccines in inflammatory bowel disease patients receiving biologic therapies. Gastroenterology. 2021;161:715–8.e4. PubMed PMC

Classen JM, Muzalyova A, Nagl S, 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. Dig Dis. 2022;40:719–27. PubMed PMC

Khan N, Mahmud N. Effectiveness of SARS-CoV-2 vaccination in a veterans affairs cohort of patients with inflammatory bowel disease with diverse exposure to immunosuppressive medications. Gastroenterology. 2021;161:827–36. PubMed PMC

Lev-Tzion R, Focht G, Lujan R, et al. . COVID-19 vaccine is effective in inflammatory bowel disease patients and is not associated with disease exacerbation. Clin Gastroenterol Hepatol. 2022;20:e1263–82. PubMed PMC

Chhibba T, Targownik LE. Is the attenuated humoral response to COVID-19 vaccination in anti-TNF users relevant? Lancet Gastroenterol Hepatol. 2022;7:280–2. PubMed PMC

Botwin GJ, Li D, Figueiredo J, et al. . Adverse events after SARS-CoV-2 mRNA vaccination among patients with inflammatory bowel disease. Am J Gastroenterol. 2021;116:1746–51. PubMed PMC

Cannatelli R, Ferretti F, Carmagnola S, et al. . Risk of adverse events and reported clinical relapse after COVID-19 vaccination in patients with IBD. Gut. 2022;71:1926–8. PubMed

Ellul P, Reves J, Abreu B, et al. . Implementation and short-term adverse events of anti-SARS-CoV-2 vaccines in inflammatory bowel disease patients: an international web-based survey. J Crohns Colitis. 2022;16:1070–8. PubMed PMC

Weaver KN, Zhang X, Dai X, et al. . Impact of SARS-CoV-2 vaccination on inflammatory bowel disease activity and development of vaccine-related adverse events: results from PREVENT-COVID. Inflamm Bowel Dis. 2022;28:1497–505. PubMed PMC

Li D, Debbas P, Cheng S, et al. . Post-vaccination symptoms after a third dose of mRNA SARS-CoV-2 vaccination in patients with inflammatory bowel disease. medRxiv. 2021; 2021.12.05.21266089. PubMed

Chanchlani N, Lin S, Chee D, et al. . Adalimumab and infliximab impair SARS-CoV-2 antibody responses: results from a therapeutic drug monitoring study in 11422 biologic-treated patients. J Crohns Colitis. 2022;16:389–97. PubMed PMC

Kennedy NA, Goodhand JR, Bewshea C, et al. . Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab. Gut. 2021;70:865–75. PubMed

Lin S, Kennedy NA, Saifuddin A, 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. Nat Commun. 2022;13:1379. PubMed PMC

Li D, Xu A, Mengesha E, 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. medRxiv. 2021; 2021.12.08.21267444.

Reuken PA, Andreas N, Grunert PC, Glöckner S, Kamradt T, Stallmach A. T cell response after SARS-CoV-2 vaccination in immunocompromised patients with inflammatory bowel disease. J Crohns Colitis. 2022;16:251–8. PubMed PMC

Wellens J, Colombel JF, Satsangi JJ, Wong S-Y. SARS-CoV-2 vaccination in IBD: past lessons, current evidence, and future challenges. J Crohns Colitis. 2021;15:1376–86. PubMed PMC

Response to Letter to the Editor: Post-Vaccination Immunogenicity of BNT162b2 SARS-CoV-2 Vaccine and Its Predictors in Pediatric Inflammatory Bowel Disease