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 SARS-CoV-2 vaccine. We investigated serological responses following 1 st , 2 nd , and 3 rd 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 1 st dose vaccination, 1–8 weeks after 2 nd dose, 8 or more weeks after 2 nd dose, and at least 1 week after 3 rd 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-1 st dose to 1–8 weeks post-2 nd dose (81.6%, 1814 AU/mL vs. 98.7%, 9229 AU/mL, p <0.001), decreased after 8 weeks post-2 nd dose (94.9%, 3002 AU/mL, p <0.001), and rebounded post-3 rd dose (99.6%, 14639 AU/mL, p <0.001). Prednisone was the only IBD-related medication associated with diminished antibody response after 3 rd -dose vaccination (FC: 0.07 [95% CI: 0.02, 0.20]). Antibody levels steadily decline following the 2 nd (FC: 0.92 [95% CI: 0.90, 0.94] per week) and 3 rd 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 3 rd dose of the vaccine should be monitored in future studies.