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Previous work demonstrated that patients with inflammatory bowel disease (IBD) who were treated with anti-TNF biologics exhibited decreased Spike-specific antibody responses compared with patients with IBD treated with anti-IL-12/23 or healthy controls, even after 4 doses of mRNA vaccine.METHODS Here we analyzed humoral responses to SARS-CoV-2 immunization using single-cell RNA-Sequencing and flow cytometry of Spike-specific memory B cells (MBC), as well as avidity measurements of plasma antibodies from patients with IBD treated with anti-TNF or anti-IL-12/23 and from people in the healthy control group.RESULTS We observed decreased somatic hypermutation in the B cell receptors of Spike-specific MBCs and decreased antigen-specific MBC accumulation following SARS-CoV-2 mRNA vaccination in patients with IBD treated with anti-TNF, compared with patients with IBD treated with anti-IL-12/23 or people in the healthy control group