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]

Jayne Doherty; Neil O'Morain; Roisin Stack; Miriam Tosetto; Rosanna Inzitiari; Sophie O'Reilly; Lili Gu; Juliette Sheridan; Garret Cullen; Edel Mc Dermott; Maire Buckley; Gareth Horgan; Hugh Mulcahy; Margaret Walshe; Elizabeth J Ryan; Virginie Gautier; John Prostko; Edwin Frias; David Daghfal; Peter Doran; Colm O'Morain; Glen A Doherty

doi:10.1093/ecco-jcc/jjad065

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]

J Crohns Colitis. 2023 Oct 20;17(9):1445-1456. doi: 10.1093/ecco-jcc/jjad065.

Authors

Jayne Doherty^{1

2

3}, Neil O'Morain^{1

2}, Roisin Stack^{1

2}, Miriam Tosetto², Rosanna Inzitiari², Sophie O'Reilly⁴, Lili Gu⁴, Juliette Sheridan^{1

2}, Garret Cullen^{1

2

3}, Edel Mc Dermott¹, Maire Buckley^{1

5}, Gareth Horgan^{1

6}, Hugh Mulcahy^{1

2}, Margaret Walshe^{1

2

3}, Elizabeth J Ryan⁷, Virginie Gautier⁴, John Prostko⁸, Edwin Frias⁸, David Daghfal⁸, Peter Doran², Colm O'Morain^{9

3}, Glen A Doherty^{1

2

3}

Affiliations

¹ Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
² School of Medicine, University College Dublin, Dublin, Ireland.
³ INITIative IBD Research Network (www.initiativeibd.ie).
⁴ Centre for Experimental Pathogen Host Research, School of Medicine, University College Dublin, Ireland.
⁵ St Michaels Hospital, Dun Laoghaire, Co Dublin, Ireland.
⁶ St Columcille's Hospital, Loughlinstown, Co Dublin, Ireland.
⁷ Department of Biological Sciences, Health Research Institute, University of Limerick, Limerick, Ireland.
⁸ Abbott Laboratories, Abbott Diagnostics, Lake Forest, IL 60045, USA.
⁹ Beacon Hospital, Sandyford, Co. Dublin and Trinity College Dublin, Ireland.

PMID: 37018462
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.

Keywords: COVID-19 vaccination; Inflammatory bowel disease; immune response; memory B-cell response.

Grants and funding

University College Dublin