Reduced Serological Response to COVID-19 Booster Vaccine is Associated with Reduced B Cell Memory in Patients With Inflammatory Bowel Disease; VARIATION [VAriability in Response in IBD AgainsT SARS-COV-2 ImmunisatiON]

• Published in: Journal of Crohn's and colitis Vol. 17; no. 9; pp. 1445 - 1456
• Main Authors: Doherty, Jayne, O’Morain, Neil, Stack, Roisin, Tosetto, Miriam, Inzitiari, Rosanna, O’Reilly, Sophie, Gu, Lili, Sheridan, Juliette, Cullen, Garret, Mc Dermott, Edel, Buckley, Maire, Horgan, Gareth, Mulcahy, Hugh, Walshe, Margaret, Ryan, Elizabeth J, Gautier, Virginie, Prostko, John, Frias, Edwin, Daghfal, David, Doran, Peter, O’Morain, Colm, Doherty, Glen A
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 20-10-2023
• Subjects: Inflammatory bowel disease; COVID-19 vaccination; immune response; memory B-cell response; Memory B-cell response
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjad065

Abstract
Background and Aims
Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2.
Methods
This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture.
Results
Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p < 0.001] as was ACE2 binding inhibition [p < 0.001]. IBD patients previously infected with COVID-19 [30%] had similar quantitative antibody response as HCs previously infected with COVID-19 [p = 0.12]. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor [anti-TNF] agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 [p = 0.01]. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses.
Conclusions
Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.