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).

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) have an attenuated response to initial COVID-19 vaccination. We sought to characterise the impact of IBD and its treatment on responses after third vaccine against SARS-CoV-2. METHODS: 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 neutralisation of binding to Angiotensin-Converting-Enzyme (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 is significantly lower than HCs (7,862 versus 19,622 AU/mL, p <0.001) as is ACE2 binding inhibition (p <0.001). IBD patients previously infected with COVID-19 (30%) have similar quantitative antibody response as HCs previously infected with COVID-19 (p = 0.12). Lowest anti-SP IgG titres and neutralisation are seen in IBD patients on anti-TNF agents, without prior COVID-19 infection but all IBD patients show 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 < 65ng/ml are associated with significantly lower serologic response. 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.

Reduced Serological Response to COVID-19 Vaccines in Patients with IBD is Further Diminished by TNF Inhibitor Therapy; Early Results of the VARIATION study [VAriability in Response in IBD Against SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Evidence suggests patients with inflammatory bowel disease [IBD] receiving TNF antagonists have attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and of various medications for treatment of IBD on antibody responses to vaccination against COVID-19. METHODS: Patients with IBD [n = 270] and healthy controls [HC, n = 116] were recruited prospectively, and quantitative antibody responses were assessed following COVID-19 vaccination. The impact of IBD and of medications for treatment of IBD on vaccine response rates was investigated. RESULTS: Of HC, 100% seroconverted following complete vaccination with two vaccine doses; 2% of patients with IBD failed to seroconvert. Median anti-spike protein [SP] immunoglobulin [Ig]G levels following complete vaccination in our IBD cohort was significantly lower than among HC [2613 AU/mL versus 6871 AU/mL, p ≤0.001]. A diagnosis of IBD was independently associated with lower anti-SP IgG levels [ß coefficient -0.2, p = 0.001]. Use of mRNA vaccines was independently associated with higher anti-SP IgG levels [ß coefficient 0.25, p ≤0.001]. Patients with IBD receiving TNF inhibitors had significantly lower anti-SP IgG levels [2445 AU/mL] than IBD patients not receiving TNF inhibitors [3868 AU/mL, p ≤0.001]. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared with HC [3868 AU/mL versus 8747 AU/mL, p = 0.001]. CONCLUSIONS: Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy negatively affects anti-SP IgG levels further. Patients who do not seroconvert following vaccination are a particularly vulnerable cohort. Impaired responses to vaccination in our study highlight the importance of booster vaccination programmes for patients with IBD.

Review Article: vaccination for patients with inflammatory bowel disease during the COVID-19 pandemic.

BACKGROUND: Poor immune responses are frequently observed in patients with inflammatory bowel disease (IBD) receiving established vaccines; risk factors include immunosuppressants and active disease. AIMS: To summarise available information regarding immune responses achieved in patients with IBD receiving established vaccines. Using this information, to identify risk factors in the IBD population related to poor vaccine-induced immunity that may be applicable to vaccines against COVID-19. METHODS: We undertook a literature review on immunity to currently recommended vaccines for patients with IBD and to COVID-19 vaccines and summarised the relevant literature. RESULTS: Patients with IBD have reduced immune responses following vaccination compared to the general population. Factors including the use of immunomodulators and anti-TNF agents reduce response rates. Patients with IBD should be vaccinated against COVID-19 at the earliest opportunity as recommended by International Advisory Committees, and vaccination should not be deferred because a patient is receiving immune-modifying therapies. Antibody titres to COVID-19 vaccines appear to be reduced in patients receiving anti-TNF therapy, especially in combination with immunomodulators after one vaccination. Therefore, we should optimise any established risk factors that could impact response to vaccination in patients with IBD before vaccination. CONCLUSIONS: Ideally, patients with IBD should be vaccinated at the earliest opportunity against COVID-19. Patients should be in remission and, if possible, have their corticosteroid dose minimised before vaccination. Further research is required to determine the impact of different biologics on vaccine response to COVID-19 and the potential for booster vaccines or heterologous prime-boost vaccinations in the IBD population.