Associations Between Body Mass Index and Serological Responses to SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease

Introduction: Vaccines have been shown effective regardless of Body Mass Index (BMI), obesity may impact antibody levels compared to healthy weight subjects. The durability of vaccine response in people with obesity has not been definitively studied in those IBD. This study aims to determine the association between elevated BMI and serological responses (SR) to SARS-CoV-2 vaccination in individuals with IBD. Methods: SARS-CoV-2 vaccinated (≥ 2 doses) adults with IBD were recruited from the STOP COVID-19 IBD cohort. Patient height and weight recorded at recruitment were used to calculate BMI. Individuals were stratified into “obese” (BMI ≥30) and “normal to overweight” (BMI 18.5-30) groups according to the CDC Obesity classification. IgG antibodies to the spike protein of SARS-CoV-2 (anti-S) were assessed using the Abbott Architect SARS-CoV-2 IgG II Quant assay at 1–8 weeks after 1st dose vaccination, and 1–8 weeks and 8+ weeks after 2nd, 3rd, and 4th dose vaccination. Sex, age, IBD type, and medication status at 1st dose of vaccine were collected via chart review and compared between BMI groups using Chi-square tests for frequencies or Mann-Whitney U test for means. Positive SR (≥50 AU/mL) rates were compared between BMI groups using two-sample proportion tests. Anti-S concentrations, reported as geometric mean titres (GMT), were compared using Mann Whitney-U tests. For timepoints with significant GMT differences, multivariable linear regression was used to model the association between obesity and anti-S concentration, adjusted for age, sex, IBD type, medication class, and prior COVID-19 infection. Results: 105 individuals have with obesity and 362 non-obese were recruited. SR rates were similar between groups across all vaccine doses. Anti-S titres were significantly increased for individuals with BMI ≥30 following 1–8 weeks post-3rd dose vaccination (18721 vs. 11304 AU/mL). However, no significant GMT differences were observed for other timepoints (Table 1, Figure 1). This association between obesity and increased anti-S held after adjusting for confounders within a regression model (Geometric mean ratio: 1.61; 95% CI: 1.16, 2.22; P=0.004). Conclusion: Antibody levels in obese IBD patients were similar to non-obese with the exception of a higher initial response following 3rd vaccine dose. Future studies are necessary to explore clinical, pharmacodynamic, or immunological factors explaining a higher SR in obese individuals with IBD, and whether this confers greater protection. Table 1. - Overall patient characteristics, seroconversion, and GMT with associated 95% CIs stratified by BMI and vaccination timepoint and associated univariate analyses Characteristic Time point BMI ≥ 30 (n = 105) BMI 18.5-30 (n = 362) P-value Male sex, n (%) Overall 36 (34.3%) 187 (51.7%) 0.002 Mean age (SD) 51.2 (12.7) 48.7 (14.8) 0.117 Medication class, n (%) No immunosuppressives 11 (10.5%) 40 (11.0%) – Anti-TNF only 33 (31.4%) 128 (35.4%) 0.869 Immunomodulator only 2 (1.9%) 9 (2.5%) 0.802 Vedolizumab only 18 (17.1%) 34 (9.4%) 0.141 Ustekinumab only 20 (19.1%) 80 (22.1%) 0.821 Tofacitinib only 5 (4.8%) 1 (0.3%) 0.001 Combination therapy† 14 (13.3%) 62 (17.1%) 0.662 Corticosteroids‡ 2 (1.9%) 8 (2.2%) 0.912 IBD type, n (%) Crohn’s disease 76 (72.4%) 257 (71.0%) 0.632 Ulcerative colitis 28 (26.7%) 96 (26.5%) IBD-Unclassified 1 (0.9%) 9 (2.5%) Seroconversion, n/N (%) Post-1st 43/50 (86.0%) 147/182 (80.8%) 0.395 Post-2nd (1–8 weeks) 66/66 (100.0%) 233/237 (98.3%) 0.288 Post-2nd (8+ weeks) 52/55 (94.6%) 173/181 (95.6%) 0.750 Post-3rd (1–8 weeks) 59/59 (100.0%) 174/175 (99.4%) 0.561 Post-3rd (8+ weeks) 67/67 (100.0%) 237/239 (99.2%) 0.453 Post-4th (1–8 weeks) 21/21 (100.0%) 62/63 (98.4%) 0.561 Post-4th (8+ weeks) 20/20 (100.0%) 57/59 (96.6%) 0.404 Post-4th (Overall) 29/29 (100.0%) 82/84 (97.6%) 0.402 GMT (95% CI) Post-1st 243 (153, 387) 269 (208, 348) 0.851 Post-2nd (1–8 weeks) 5198 (3805, 7103) 3775 (3124, 4563) 0.151 Post-2nd (8+ weeks) 1223 (804, 1861) 1088 (842, 1405) 0.633 Post-3rd (1–8 weeks) 18721 (14065, 24918) 11304 (9456, 13512) 0.003 Post-3rd (8+ weeks) 5436 (3632, 8136) 4070 (3314, 4999) 0.119 Post-4th (1–8 weeks) 21202 (12236, 36739) 13626 (9982, 18600) 0.147 Post-4th (8+ weeks) 7496 (3799, 14790) 4558 (2971, 6993) 0.269 Post-4th (Overall) 15375 (9234, 25598) 9808 (7105, 13540) 0.184 *Indicates reference group.†Combination therapy refers to any combination of two or more of the following therapies: anti-TNF, immunomodulators, vedolizumab, ustekinumab, and tofacitinib.‡Oral prednisone at any dose or with any other drug class. Figure 1.: Anti-SARS-CoV-2 antibody concentration per vaccine category stratified by BMI between 18.5 and 30 (circles) and ≥30 (triangles). Black circles represent GMTs while narrow black bars represent bounds of 95% CI associated with each GMT. Solid blue line represents threshold for positive seroconversion (50 AU/mL).