Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease

Brenner, Erica J.; Weaver, Kimberly N.; Zhang, Xian; Kastl, Arthur J.; Strople, Jennifer A.; Adler, Jeremy; Dubinsky, Marla C.; Bousvaros, Athos; Watkins, Runa; Dai, Xiangfeng; Chen, Wenli; Cross, Raymond K.; Higgins, Peter D.R.; Ungaro, Ryan C.; Bewtra, Meenakshi; Bellaguarda, Emanuelle A.; Farraye, Francis A.; Chun, Kelly Y.; Zikry, Michael; Bastidas, Monique; Firestine, Ann; Craig, Riley G.; Boccieri, Margie E.; Long, Millie D.; Kappelman, Michael D.

doi:10.1016/j.cgh.2024.02.001

Clinical Gastroenterology and Hepatology

2024

DOI: 10.1016/j.cgh.2024.02.001

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Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease

Erica J. Brenner,

Kimberly N. Weaver,

Xian Zhang

et al.

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Cited by 4 publications

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Durable Immune Response and Long-term Efficacy of COVID-19 Vaccination in Children With Inflammatory Bowel Disease

Kastl,

Brenner,

Weaver

et al. 2024

Inflammatory Bowel Diseases

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Background Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. Methods We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. Results We enrolled 298 participants (mean age 11.9 ± 3.82, 50% female, 67% Crohn’s disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001). Conclusions SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.

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Durable Immune Response and Long-term Efficacy of COVID-19 Vaccination in Children With Inflammatory Bowel Disease

Kastl,

Brenner,

Weaver

et al. 2024

Inflammatory Bowel Diseases

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XBB.1.5‐Adapted COVID‐19 mRNA Vaccines but Not Infections With Previous Omicron Variants Boost Neutralisation Against the SARS‐CoV‐2 JN.1 Variant in Patients With Inflammatory Bowel Disease

Woelfel,

Dütschler,

Junker

et al. 2024

Aliment Pharmacol Ther

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BackgroundVariant‐adapted COVID‐19 vaccines are recommended for patients with inflammatory bowel disease (IBD). However, many patients rely on pre‐existing immunity by original vaccines or prior infections.AimTo assess whether such immunity sufficiently combats the highly immune‐evasive SARS‐CoV‐2 JN.1 variant.MethodsUtilising two longitudinal cohorts, we evaluated immunity against JN.1 induced by original vaccines (IBD: n = 98; healthy: n = 48), omicron breakthrough infection (IBD: n = 55; healthy: n = 57) or XBB.1.5‐adapted vaccines (IBD: n = 18). Neutralisation and anti‐receptor‐binding domain (RBD) IgG levels against wild‐type SARS‐CoV‐2 and JN.1 were assessed using multiplex immunoassays. Study outcomes were wild‐type and JN.1 neutralisation following three doses of original mRNA vaccines, stratified by immunosuppressive therapy (primary outcome), and JN.1 neutralisation following third‐dose breakthrough infection or a fourth dose of XBB.1.5‐adapted mRNA vaccines (secondary outcomes).ResultsFollowing original vaccines, JN.1 neutralisation was lower than wild‐type neutralisation in all study groups (healthy, anti‐TNF and non‐anti‐TNF; each p < 0.001); most individuals lacked JN.1 neutralisation (healthy: 97.9%; anti‐TNF: 98.3% and non‐anti‐TNF: 92.3%). Confounder‐adjusted multivariable modelling strongly associated anti‐TNF therapy with low levels of anti‐JN.1‐RBD IgG (fold‐change 0.48 [95% CI 0.39–0.59]). JN.1 neutralisation was similar in patients with or without breakthrough infection (anti‐TNF, non‐anti‐TNF; each p > 0.05); neutralisation failure was 100% despite breakthrough infection. XBB.1.5‐adapted vaccines enhanced JN.1 neutralisation (p < 0.001) and reduced neutralisation failure rates in patients with IBD (94.4% pre‐vaccination vs. 44.4% post‐vaccination; p = 0.003).ConclusionsOnly variant‐adapted vaccines protect against emerging SARS‐CoV‐2 variants. Patients with IBD and healthy individuals without recent vaccination may lack protection against the JN.1 subvariant KP.3 which causes current COVID‐19 surges.

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Systemic and Mucosal Immunogenicity of Monovalent XBB.1.5-Adapted COVID-19 mRNA Vaccines in Patients with Inflammatory Bowel Disease

Woelfel,

Dütschler,

Junker

et al. 2024

Vaccines

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Recently updated COVID-19 mRNA vaccines encode the spike protein of the omicron subvariant XBB.1.5 and are recommended for patients with inflammatory bowel disease (IBD) on immunosuppressive treatment. Nonetheless, their immunogenicity in patients with IBD against rapidly expanding virus variants remains unknown. This prospective multicenter cohort study is the first study to investigate the immunogenicity of XBB.1.5-adapted vaccines in patients with IBD. Systemic and mucosal antibodies targeting the receptor-binding domains (RBDs) of the omicron subvariants XBB.1.5, EG.5.1, and BA.2.86, as well as their neutralization were quantified before and two to four weeks after vaccination with monovalent XBB.1.5-adapted mRNA vaccines. Vaccination increased levels of serum anti-RBD IgG targeting XBB.1.5, EG.5.1, and BA.2.86 (1.9-fold, 1.8-fold, and 2.6-fold, respectively) and enhanced corresponding neutralization responses (2.3-fold, 3.1-fold, and 3.5-fold, respectively). Following vaccination, anti-TNF-treated patients had reduced virus neutralization compared to patients on treatments with other cellular targets. 11.1% and 16.7% of patients lacked EG.5.1 and BA.2.86 neutralization, respectively; all these patients received anti-TNF treatment. At mucosal sites, vaccination induced variant-specific anti-RBD IgG but failed to induce RBD-targeting IgA. Our findings provide a basis for future vaccine recommendations while highlighting the importance of frequent booster vaccine adaptation and the need for mucosal vaccination strategies in patients with IBD.

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Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease

Cited by 4 publications

References 13 publications

Durable Immune Response and Long-term Efficacy of COVID-19 Vaccination in Children With Inflammatory Bowel Disease

Durable Immune Response and Long-term Efficacy of COVID-19 Vaccination in Children With Inflammatory Bowel Disease

XBB.1.5‐Adapted COVID‐19 mRNA Vaccines but Not Infections With Previous Omicron Variants Boost Neutralisation Against the SARS‐CoV‐2 JN.1 Variant in Patients With Inflammatory Bowel Disease

Systemic and Mucosal Immunogenicity of Monovalent XBB.1.5-Adapted COVID-19 mRNA Vaccines in Patients with Inflammatory Bowel Disease

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