ABSTRACT
IMPACT OF INFLAMMATORY BOWEL DISEASE THERAPIES ON DURABILITY OF HUMORAL RESPONSE TO SARS COV-2 VACCINATION Background and Aim: Immunization against the spike protein of SARS-CoV-2 reduces the risk of severe outcomes and previous data show that most inflammatory bowel disease (IBD) patients mount SARS-CoV- 2 anti-spike (S) antibodies (Ab). However, no data exist on the durability of these antibodies over time. We sought to investigate the impact of IBD and its therapies on post-vaccination antibody response and decay rates. Methods: Data were retrospectively ed from patients with IBD who underwent one Anti-S Total Ab (Labcorp®) test ≥2 weeks post 2nd dose, between April 15th-October 19th, 2021. Analyses included t-tests/1-way ANOVA, Mood's medians tests, chi-square and Fisher-exact tests. Linear regression estimated linear log(e)(Anti-S Total Ab) decays post-vaccine dose #2 (excluding patients with COVID-19 history). Exponentiated decay coefficients (EDC) represent % change from geometric mean titer (GMT). Results: We identified 176 patients with Anti-S Total Ab (Labcorp®) titer testing following two doses of the BNT162b2 (Pfizer/BioNTech;n=111) or mRNA-1273 (Moderna;n=65) vaccines. We compared non-immunosuppressed (IS) patients (non-anti- TNF biologics/Mesalamine/Budesonide/No therapy) to patients on IS (anti-TNF-a ± immunomodulators). Patients on systemic steroids (n=7) or tofacitinib (n=7) were excluded due to low sample size. Median interval from dose #2 to titer testing was 126 days (IQR:89-162), similarly distributed among vaccine/medication groups (p=0.4). Overall GMT was 306 u/ mL (95%CI 234-401), non-significantly different between vaccines (p=0.6). Four patients had undetectable antibodies (three on tacrolimus and one on renal dialysis). One had breakthrough COVID-19 infection (S-titer=13u/mL). Patients receiving IS had significantly lower titers (mean log) for both vaccines, compared to those without IS overall (Fig 1A). Patients receiving IS had lower proportions with Anti-S Total Ab above 100U/mL, 300 U/ mL, 500U/ml and 1000U/mL at all timepoints up to 6 months post-second dose (Fig 1B). Patients on IS had significant titer decay (Fig 1C, n=42, EDC 1.8%/day, p=0.012, t½≈38 days) and was significantly faster (Δ-slope p<0.05) than those not on IS (n=74, p=0.058, EDC 0.05%/day, t½≈153 days). Among anti-TNF monotherapy patients (Fig 1D), there was faster decay in BNT162b2 (n=25, EDC 2.4%/day, p=0.002, t½≈28 days) compared to mRNA- 1273 (n=10, EDC 0.9%/day, p=0.188, t½»76 days), with near-significant Δ-slope (p=0.109). Conclusions: While IBD patients initially exhibit robust responses to SARS-CoV-2 vaccination, far fewer patients on IS achieve high titers. Titers decay faster in those on anti-TNF agents, and data suggests this decay is more pronounced with BNT162b2 (Figure Presented)
ABSTRACT
Background: Several SARS-CoV-2 vaccines are highly effective in preventing most infections, serious disease, hospitalization, and death from COVID-19 in the general population, but data regarding their use and efficacy in patients with inflammatory bowel disease (IBD) are limited. In this study we assessed the use patterns and efficacy of SARS-CoV-2 vaccines in patients with IBD. Methods: We established a multicenter matched case-control cohort of patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] and COVID-19 between February 2020 and December 2020 for the Surveillance of COVID-19 Impact on Long- Term Outcomes in IBD (SCOUT IBD) study. Cases were defined by the presence of COVID- 19-related symptoms and confirmatory SARS-CoV-2 PCR or IgG testing and non-COVID controls were defined as absence of symptoms and both a negative PCR and IgG in 2020. Cases were matched 1:1 to controls based on age, sex and IBD type. Data were collected on vaccine administration in 2021 and incidence of interval COVID-19 (defined as above) between January and September 2021. Results: The total cohort included 502 patients with IBD [UC (n=222, 44%), CD (n=278, 55%), IBD-undefined (n=2, 1%)] of whom 251 had a history of COVID-19 in 2020. The overall vaccination rate was 61% (n=306) with 189 (62%) patients receiving Pfizer-BioNTech, 101 (33%) Moderna, and 12 (4%) Johnson & Johnson. Vaccinated patients were more likely to be older (P=0.02), female (P=0.07), have a co-morbidity (cardiovascular, respiratory, renal) (P=0.04), or currently be on a biologic (P=0.01), and less likely to have had prior COVID-19 (P<0.001) than patients who did not get vaccinated (Table 1). The overall incidence of interval COVID-19 was 1.6% (N=8), with an infection rate of 0.3% (1/311) in vaccinated patients vs. 3.7% (7/184) in unvaccinated patients (P<0.01). Of infections occurring in unvaccinated patients, 1/7 (14.2%) was severe and required hospitalization requiring ICU admission, and the breakthrough infection in the vaccinated patient was mild and self-limited. COVID-19 reinfection occurred in one patient (0.4%) with prior COVID-19 who was unvaccinated. Under multivariable logistic regression, COVID-19 vaccination (aOR 0.05, 95% CI 0.01-0.41) and prior COVID-19 infection (OR 0.07, 95% CI 0.01-0.63) were highly protective against interval COVID-19. Conclusion: COVID-19 vaccines are effective in patients with IBD and markedly reduce the incidence of COVID-19. Prior COVID-19 is also protective against subsequent infection, although re-infections may occur at a very low rate. These results reaffirm the importance of COVID-19 vaccination in patients with IBD.(Table Presented)(Table Presented)
ABSTRACT
Background: Inflammatory bowel disease (IBD) and IBD-related biologic therapies are not associated with worse outcomes of Coronavirus Disease 2019 (COVID-19), however, data are lacking regarding the long-term impact of COVID-19 and its inflammatory sequelae on the disease course of IBD. We aimed to investigate the long-term outcomes of patients with IBD and COVID-19. Methods: We performed a multicenter matched case-control study of patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] and COVID-19 between February 2020 and December 2020 at 5 large health systems. Cases were defined by the presence of COVID-19-related symptoms and confirmatory SARS-CoV-2 PCR or IgG testing. Non-COVID controls were defined as absence of symptoms and both a negative PCR and IgG during the study entry period. Cases were matched 1:1 to controls based on age, sex and IBD type. The primary composite outcome was IBD-related hospitalization or surgery, and outcomes were sub-stratified by COVID-19 severity. Results: We identified 251 cases with IBD [UC (n=111, 44%), CD (n=139, 55%)] and confirmed COVID-19, matched with 251 non-COVID-19 IBD controls, with a median follow-up of 394 days. COVID-19 patients had higher rates of prior IBD-related hospitalizations (36% vs. 27%;P=0.03), corticosteroid use (75% vs. 65%;P=0.06), and biologic exposure (73% vs. 64%;P=0.04) than controls. There were no differences in UC extent or CD phenotype between groups. In COVID-19 positive patients, the most common symptoms were fever (61%), cough (48%), fatigue (30%) and diarrhea (28%). Severe COVID-19 (defined as hospitalization, ICU requirement or mechanical ventilation) occurred in 16% (n=39) of cases. The primary composite outcome of IBD-related hospitalization or surgery occurred in 12% (n=38) of cases vs. 15% (n=29) of controls (P=0.24;Table 1). When further stratified by COVID-19 severity, the incidence of the primary composite outcome was highest in patients with severe COVID-19, followed by controls and non-severe COVID-19 (Figure 1). Under multivariate Cox regression, severe COVID-19 remained a predictor of worse IBD outcomes (aHR 2.09, 95% CI 0.91-4.86) whereas non-severe COVID-19 was associated with decreased risk (aHR 0.52, 95% CI 0.28- 0.99). Prior IBD-related hospitalization or surgery (aHR 3.10, 95% CI 1.70-6.57) and current steroid use (aHR 2.17, 95% CI 0.95-4.94) were also predictive of worse IBD outcomes. Conclusion: In this matched case-control study, a history of any COVID-19 infection did not appear to exacerbate the course of IBD, however, severe COVID-19 was associated with worse IBD outcomes. These data suggest that the inflammatory sequelae of COVID-19 may adversely impact the subsequent disease course of IBD. Further studies are required to confirm these associations, which underscore the importance of COVID-19 mitigation measures.(Table Presented) (Figure Presented)