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Serological Responses to the First Three Doses of SARS-CoV-2 Vaccination in Inflammatory Bowel Disease: A Prospective Cohort Study

Background Individuals with inflammatory bowel disease (IBD) who are immunocompromised may have a reduced serological response to the SARSCoV2 vaccine. We investigated serological responses following 1st, 2nd, and 3rd doses of SARS-CoV-2 vaccination in those with IBD. Methods A prospective cohort study of persons with IBD (n = 496) assessed serological response 1-8 weeks after 1st dose vaccination, 1-8 weeks after 2nd dose, 8 or more weeks after 2nd dose, and at least 1 week after 3rd dose. Seroconversion and geometric mean titer (GMT) with 95% confidence intervals (CI) were assessed for antibodies to the SARS-CoV-2 spike protein. Multivariable linear regression models assessed the adjusted fold change (FC) in antibody levels. Results Seroconversion and GMT increased from post-1st dose to 1-8 weeks post-2nd dose (81.6%, 1814 AU/mL vs. 98.7%, 9229 AU/mL, p<0.001), decreased after 8 weeks post-2nd dose (94.9%, 3002 AU/mL, p<0.001), and rebounded post-3rd dose (99.6%, 14639 AU/mL, p<0.001). Prednisone was the only IBD-related medication associated with diminished antibody response after 3rd-dose vaccination (FC: 0.07 [95% CI: 0.02, 0.20]). Antibody levels steadily decline following the 2nd (FC: 0.92 [95% CI: 0.90, 0.94] per week) and 3rd dose (FC: 0.88 [95% CI: 0.84, 0.92] per week) of the SARS-CoV-2 vaccine. Conclusion A three-dose regimen of vaccination to SARS-CoV-2 yields a robust antibody response for those with IBD across all classes of IBD therapies except for prednisone. The decaying antibody levels following the 3rd dose of the vaccine should be monitored in future studies.