EXPLORING FACTORS ASSOCIATED WITH SEROLOGICAL RESPONSE TO SARS-COV-2 VACCINES IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE: INTERACTIVE VISUALIZATION METHODS FOR MULTIDIMENSIONAL DATA
Authors: Hracs Lindsay , Quan Joshua , Ma Christopher , Panaccione Remo , Sharifi Nastaran , Herauf Michelle , Markovinovic Ante , Coward Stephanie , Windsor Joseph , Caplan Lea , Gorospe Julia , Ernest-Suarez Kenneth , Ingram Richard , Holodinsky Jessalyn , Bernstein Charles , Mahoney Douglas , Bernatsky Sasha , Benchimol Eric , Kaplan Gilaad 
Published: January 2024

Abstract

BACKGROUND
SARS-CoV-2 vaccine response may be reduced in seniors (age 65+) with inflammatory bowel disease (IBD) and those on anti-TNF therapy. A challenge of the COVID-19 era has been conveying rapid-evolving health information, especially for groups with higher risk of poor outcomes of COVID-19 such as seniors and immunocompromised individuals.

AIM
To develop sharable, interactive 3D models of the relationship of age and days from vaccine dose on serological responses to SARS-CoV-2 vaccines in people with IBD who are either on or not on anti-TNF therapy.

METHODS
A prospective cohort study of individuals with IBD (n=528) who received 1–4 doses of a COVID-19 vaccine were assessed for serological responses 1–8 weeks and 8–16 weeks following each dose using the SARS-CoV-2 IgG II Quant assay. The cohort was stratified into those on and not on anti-TNF therapy at vaccination.
We created 3D models with the plotly R package. Data were plotted as days from vaccine dose on the x-axis, age at the time of serology on the y-axis, and spike-protein antibody levels on the z-axis. Linear regressions were run with Anti-Spike IgG levels (AU/mL) as the outcome, and days from vaccine and age at serology as continuous exposures. Results were visualized as regression planes in 3D models. To share our visualizations, we built an open-access, online, interactive dashboard (https://covid19-sero.shinyapps.io/dashboard/).

RESULTS
The dashboard allows knowledge users to make selections based on desired data stratifications, and then zoom, pan, and rotate the plot to inspect the data or download an image of the plot they generate.
Post-2nd dose samples comprised the largest dose subset in our study (n=658). Our model for post-2nd dose data shows that antibody levels significantly decrease by 20.9 (AU/mL) per day from a dose (p&lt;0.001) and by 116.6 (AU/mL) per year increase in age (p=0.002) (Figure 1). As age increases, antibody levels significantly decrease by 107.5 (AU/mL) for those on anti-TNFs (p=0.026) and by 124.8 (AU/mL) for those not on anti-TNFs (p=0.002) (Figure 2). Those not on anti-TNFs experienced a decrease of 31.1 (AU/mL) (p&lt;0.001) per day after 2nd vaccine dose; we did not find a significant decrease over time for those on anti-TNFs (p=0.927) (Figure 2).

DISCUSSION
In people with IBD, advancing age is associated with lower antibody responses to SARS-CoV-2 vaccines; however, antibody response does not significantly decrease over time for those on anti-TNF therapy. Integrating visualizations of quantitative data with participant demographics and medical therapy in open-access, interactive web applications promotes rapid release of research findings in a format that is accessible by a maximum number of knowledge users, which is of continued importance for those with a high risk of complications resulting from COVID-19.

Figure 1 A scatterplot with post-2nd dose data for all possible data stratifications, downloaded from our online dashboard. The plot depicts decreasing trends in Anti-Spike IgG levels (AU/mL) as days from dose and participant age increase.

Figure 2 Scatterplots with post-2nd dose data comparing Anti-Spike IgG levels (AU/mL) for participants either on or not on anti-TNF therapy. Plots depict lower antibody levels for individuals with IBD on anti-TNF therapy. Panel A shows no change in antibody levels for those on anti-TNF therapy as days from vaccine dose increase and Panel B shows that antibody levels in those not on anti-TNF therapy decrease as both days from vaccine dose and age increase.