ABSTRACT
Introduction: Evidence suggests patients with inflammatory bowel disease (IBD) receiving TNF-antagonists have attenuated response to vaccination against COVID-19 {1}. Aims & Methods: We sought to determine the impact of IBD and various medications for treatment of IBD on antibody responses after 3rd vaccine dose against COVID-19. Patients with IBD (n=202) and healthy controls (HC, n= 92) were recruited prospectively. Quantitative antibody responses were assessed following COVID-19 vaccination and ACE2 binding inhibition assay to assess viral inhibition (or neutralization) were also assessed. The impact of IBD and medications for treatment of IBD on vaccine response rates was investigated. Result(s): Median age of IBD patients was 37.3 compared to 41.4 in HCs (p = 0.3). 60% of IBD patients were male compared to 23% of HCS (p =<0.001). Median time from 3rd vaccine dose to serum collection was 9.9 weeks in HCs versus 9.0 weeks in our IBD cohort (p = 0.75). 100% of HC seroconverted post 3rd vaccination. 1% (n=2) of patients with IBD failed to seroconvert. Median anti-spike protein (SP) immunoglobulin (Ig)G levels post-third vaccination in our IBD cohort was significantly lower than HC (7,862 AU/mL versus 19,622 AU/mL, p=<0.001). Median ACE2 binding inhibition (IQR) in our IBD cohort was significantly lower than HCs (97.1% (72.9 - 99.1) versus 99.9% (99.1 - 99.9), p = <0.001) with 28 (13.9%) IBD patients having ACE2 binding inhibition < 50% compared to 0 (0%) HCs (p = < 0.001). All IBD patients with ACE 2 inhibition levels < 50% were receiving biologic therapy. Breakdown of biologics received is as follows: 21 (75%) infliximab, 4 (14.2%) adalimumab, 1 (3.6%) golimumab and 1 (3.6%) vedolizumab therapy. than IBD patients not receiving TNF-inhibitors (n = 72) (10731AU/mL) (p = 0.001). Patients with IBD not receiving TNF-inhibitors still showed attenuated responses compared to HC (10730AU/mL versus 19622AU/mL p = 0.02). Conclusion(s): Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination after post booster vaccine. Use of anti-TNF therapy negatively impacts anti-SP IgG levels further. Patients who do not seroconvert post-vaccination are a particularly vulnerable cohort and causes for attenuated vaccine response need to be further investigated.
ABSTRACT
Objective: Patients with inflammatory bowel disease (IBD) have attenuated responses to current vaccinations. There is a limited body of evidence suggesting patients with IBD receiving TNF antagonists have an attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and various medications for the treatment of IBD on antibody responses to vaccination against COVID-19. Design: Patients with IBD (n=270) and healthy controls (HC, n=116) were recruited prospectively and quantitative antibody responses assessed following COVID-19 vaccination. The impact of IBD and medications for treatment of IBD on vaccine response rates was investigated. Results: All HC seroconvert post complete vaccination with two vaccine doses [100%]. A small proportion of patients with IBD failed to seroconvert [2%]. Median anti-spike protein (SP) immunoglobulin (Ig)G levels post one vaccination and complete vaccination in our IBD cohort was significantly lower than HC [2,613 AU/mL versus 6,871 AU/mL, p=<0.001] [Figure 1]. A diagnosis of IBD was independently associated with lower anti-SP IgG levels [β coefficient -0.2, p = 0.001] whereas use of mRNA vaccines was independently associated with higher anti-SP IgG levels [β coefficient 0.25, p = < 0.001]. Patients with IBD receiving anti-TNF therapy had significantly lower anti-SP IgG levels [2444.6 AU/mL] than IBD patients not receiving these agents [3867.6 AU/mL] [p = < 0.001]. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared to HC receiving a similar vaccine [p = 0.001] [Figure 2]. 58 patients had an additional follow-up serology sample at a median of 12 weeks to complete vaccination to allow assessment of the durability of the response after their initial post-vaccination IgG level. There was a significant drop in IgG levels from 3952.85 AU/mL at the first timepoint checked post-complete vaccination to 921.1 AU/mL (343.1 – 2102.7) on follow-up sampling (p = <0.001). Median anti-SP IgG levels were numerically lower in our cohort receiving anti-TNF therapy (794.8 AU/mL) compared to those not receiving anti-TNF therapy (3136.9 AU/mL) on final follow-up samples (p =0.28). HC participants with previous COVID-19 infection (n= 5) had significantly higher anti-SP IgG levels post complete vaccination (20,719.6 AU/mL) compared to IBD patients (n=4) with prior infection (3,938.2 AU/mL) (p = < 0.001). Conclusions: Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Patients with IBD who do not seroconvert post-vaccination against COVID-19 are a particularly vulnerable cohort. Use of anti-TNF therapy negatively impacts anti-SP IgG levels. Impaired responses to vaccination in our study highlights the importance of booster vaccination programmes for patients with IBD. (Figure Presented) Differences in median IgG levels across three time points (Figure Presented) Differences in median anti-SP Levels dependent on medication for treatment of IBD.