Impaired humoral, upheld cellular responses in patients with IBD after SARS-CoV-2 vaccine
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SAN DIEGO — Though patients with inflammatory bowel disease have impaired humoral response after SARS-CoV-2 vaccinations, cellular responses were maintained and comparable to those of health care workers, according to study results.
“We believe that the results of our study are overall reassuring and provide mechanistic explanation for the lack of higher COVID complications in our patients with inflammatory bowel disease, particularly with the fact that antibodies in all of our analyses were well above the positivity threshold, and that overall [T-cell receptor (TCR)] metrics representing cellular immunity were not different after adjusting for age, sex and vaccine type between IBD and a non-IBD cohort,” Gil Y. Melmed, MD, MS, director of IBD clinical research at Cedars-Sinai Medical Center, said at Digestive Disease Week 2022. “We also believe that long term correlations with breakthrough infections are needed, but we really need to understand what is the implication of a particular antibody level or TCR response with respect to protection.”
Melmed and colleagues assessed 2,367 patients with IBD (Crohn’s disease, 33.16%; ulcerative colitis, 66.84%) enrolled in a U.S. registry from 26 centers at 2, 8, 16 and 32 weeks following completion of two doses of SARS-CoV-2 mRNA vaccination. Results were then compared with 1,260 non-IBD non-immunosuppressed health care workers who participated in a parallel study.
Using SARS-CoV-2 IgG-II assay (Abbott Labs, Abbott Park, Illinois), investigators assessed plasma antibodies to the receptor binding domain of the viral spike protein. At 8 weeks, they performed T-cell clonal analysis with TCR immunosequencing (Adaptive Biotechnologies, Seattle). Reference datasets were used to quantify the breadth and depth of the T-cell clonal response. Investigators adjusted analyses for age, sex and vaccine type.
Melmed said the antibody levels were lower in the IBD cohort compared with health care works at every time point after the second dose of vaccination and it continued to decline. Similar results were noted in a sensitivity analysis which excluded patients that were not on immune-suppressive therapies.
Men had lower antibody responses compared with women, Melmed noted. Additionally, older health care workers had lower antibody responses at every timepoint, whereas this was not observed in the IBD cohort. At 8 weeks, no difference was observed between IBD patients and health care workers with regard to TCR breadth and depth. Similar results were observed in a sensitivity analysis among patients on or not on any form of immunosuppression therapy.
“These age and sex differences that we're seeing when we broke it down in the health care worker cohort were actually not seen in IBD patients, but also to point out that lower antibodies — even in the IBD patients — were still well above the positivity threshold in every analysis that we did,” Melmed said.
The cohorts were not different with regard to clonal breath; however, men compared with women with IBD had lower TCR response with respect to clonal depth. When researchers looked at age, again with respect to clonal depth, older patients with IBD had lower responses compared with younger patient; however, this was not seen among health care workers.
Melmed concluded, “Finally, this question which I'll leave for the audience, is our booster strategies with IBD, should they be different than the general population if in fact, their immune responses to vaccines are as robust as we found them to be?”
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Melmed G, et al. Abstract 653. Presented at: Digestive Disease Week; May 21-24, 2022; San Diego (hybrid meeting).
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