key: cord-1016764-ylx39jzo
authors: Charilaou, Paris; Tricarico, Christopher; Battat, Robert; Scherl, Ellen J.; Longman, Randy S.; Lukin, Dana J.
title: Impact of Inflammatory Bowel Disease Therapies on Durability of Humoral Response to SARS CoV-2 Vaccination
date: 2021-12-09
journal: Clin Gastroenterol Hepatol
DOI: 10.1016/j.cgh.2021.12.007
sha: b108d5340e9d56808019d7677d7d8bca80151ce5
doc_id: 1016764
cord_uid: ylx39jzo

Immunization against the spike protein of SARS-CoV-2 reduces transmission1,2 and severe outcomes. However, little is known regarding the impact of immune-mediated diseases and immunosuppressive medications on the efficacy of vaccination. Vaccination immunity is transient, with breakthrough cases increasing at longer time intervals since the last dose.3,4 Although there are data on SARS-CoV-2 vaccine on early seroconversion in patients with inflammatory bowel disease (IBD),5 no data in the same cohort exist describing the durability of these antibodies over time. We sought to investigate the impact of IBD and its therapies on postvaccination antibody response and kinetics of immunogenicity decline, because these findings may better inform clinical guidelines and recommendations on precautions and booster vaccination.

Immunization against the spike protein of SARS-CoV-2 reduces transmission 1, 2 and severe outcomes. However, little is known regarding the impact of immune-mediated diseases and immunosuppressive medications on the efficacy of vaccination. Vaccination immunity is transient, with breakthrough cases increasing at longer time intervals since the last dose 3, 4 . While there are data on SARS-CoV-2 vaccine on early seroconversion in inflammatory bowel disease (IBD) patients 5 , no data in the same cohort exist describing the durability of these antibodies over time.

We sought to investigate the impact of IBD and its therapies on post-vaccination antibody response and kinetics of immunogenicity decline, as these findings may better inform clinical guidelines and recommendations on precautions and booster vaccination.

Within a prospectively followed cohort of 195 patients with IBD who underwent one Anti-S Total Ab titer test at a non-predetermined time, between April 15 th and October 19 th 2021, 185 had measured titers following both doses of the BNT162b2 (Pfizer, BioNTech; 60%, n=111) or mRNA-1273 (Moderna; 35.1%, n=65) vaccines, and 9 (4.6%) the JNJ-78436735 vaccine (Janssen Pharmaceutical Companies; excluded from analyses due to low sample size). All vaccine doses were given at recommended dosing intervals. We divided the patients into two main medication groups: vedolizumab (VDZ)/ustekinumab (UST)/Mesalamine/Budesonide/No therapy as Group 1 and those on anti-TNF-α ± Immunomodulators (IMM) as Group 2. There were seven patients on corticosteroids (prednisone ≥20mg/day or equivalent within 30 days of dose 1) and seven on tofacitinib, which we excluded from main analyses given low sample sizes. VDZ, UST, and Mesalamine/Budesonide/No therapy were grouped together to improve sample size since antibody titer trends between all three were similar on preliminary analysis (Supplementary Figure 1A) . Patient characteristics and peri-vaccination disease activity approximated by surrogate markers (Albumin, C-Reactive Protein, Fecal Calprotectin) are described in Supplementary Table 1 .

Comparisons of mean loge(Anti-S Total Ab) across subgroups revealed significant differences between medication Groups 1 and 2, in both BNT162b2 and mRNA-1273 recipients ( Figure 1A ).

Comparisons among four arbitrarily-selected titer thresholds, at different timepoints and overall, showed significantly lower proportions of patients in Group 2 that mounted Anti-S Total Ab above each threshold, with statistically significant difference persisting up to Anti-S Total Ab ≥ 300 u/mL for at least 4 months after dose #2, while comparisons after 6 months exhibited large numerical differences without reaching statistical significance due to sample size ( Figure 1B ).

There was significant decay observed in Group 2 (n=42, exponentiated decay coefficient [EDC] 1.8%/day, p=0.012; estimated half-life 38 days) and it was significantly faster (Δ-slope p=0.045) than Group 1 (n=74, p=0.058, EDC 0.05%/day, estimated half-life 153 days), as shown in Figure   1C . Figure 1D shows the differences between the two mRNA vaccines among patients receiving anti- titer response has been suggested to positively impact long-term immunity 9 . The above, and together with our findings, suggest that the majority of IBD patients still carry a theoretical risk of breakthrough infection after vaccination, but especially those on Anti-TNF-α agents (<20% with Anti-S Total Ab ≥500u/mL at ≥2 months after dose #2), Furthermore, among the anti-TNF-αtreated patients, titer decay was 2.7 times faster in BNT162b2 vaccine recipients compared to the mRNA-1273 vaccine, thus potentially exposing to earlier breakthrough-infection risk. We thus agree that augmented vaccine dosing regimens as recommended by CDC 10 , may be needed for IBD patients, especially those on anti-TNF-α agents and possibly BNT162b2 recipients, although more data are needed to confirm the latter. October 19 th 2021. We collected all patients with IBD who had "SARS-CoV-2 Semi-Quantitative Total Antibody Spike" test (LabCorp test #164090, an electrochemiluminescence immunoassay).

The data was then quality-controlled via manual chart review. The study was approved by the Institutional Review Board.

Missing values were not imputed due to sample size limitation (n=185), to ensure data validity.

Continuous variables were analyzed using the t-test and Mood's medians test for normally and non-normally distributed data, respectively. Categorical variables were analyzed using chisquare or Fisher-exact tests. Multiple comparisons were done using one-way ANOVA, with Bonferroni correction to adjust for alpha-error inflation. The main outcome of interest, Anti-S Total Ab titer, was presented as a geometric mean titer or log-transformed (with base e), given its log-normal distribution and to allow linear modelling on its otherwise non-normally distributed residuals should be left untransformed. Robust linear regression, which is robust to potential outliers and thus allowing to include all available data, was used to fit linear trends among various comparison groups to assess the linear ln(Anti-S Total Ab) decay since dose #2 of 

Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States

Mean Albumin (g/dL