Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

Original languageEnglish
Article number1186
Issue number8
StatePublished - Aug 2022


FundersFunder number
Crohn’s and Colitis Foundation of Israel
European Federation of Crohn’s and Colitis Associations
Bristol-Myers Squibb
Leona M. and Harry B. Helmsley Charitable Trust
Milner Foundation
Israel Science Foundation2475/19, 1422/18, 401/18, 3711/20


    • COVID-19
    • anti-SARS-CoV-2 antibodies
    • circulating B cells
    • cross-reactivity
    • mRNA-BNT162b2
    • serologic response longevity
    • vaccine


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