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 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.

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.