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. 2025 Jun 23;13(7):673.
doi: 10.3390/vaccines13070673.

Factors Associated with Impaired Humoral Immune Response to mRNA Vaccines in Patients with Inflammatory Bowel Disease: A Matched-Cohort Analysis from the RisCoin Study

Katarina Csollarova  1 , Leandra Koletzko  2 , Thu Giang Le Thi  1   3 , Paul R Wratil  4   5 , Ana Zhelyazkova  6 , Simone Breiteneicher  2 , Marcel Stern  4 , Gaia Lupoli  4 , Tobias Schwerd  1 , Alexander Choukér  7 , Veit Hornung  8 , Oliver T Keppler  4   5 , Kristina Adorjan  9   10 , Helga Paula Török  2 , Sibylle Koletzko  1   11 ; Members of RisCoin Study Group
Affiliations

Factors Associated with Impaired Humoral Immune Response to mRNA Vaccines in Patients with Inflammatory Bowel Disease: A Matched-Cohort Analysis from the RisCoin Study

Katarina Csollarova et al. Vaccines (Basel). .

Abstract

Background/Objectives: The SARS-CoV-2 pandemic challenged patients with inflammatory bowel disease (IBD) under immunosuppressive therapies. We used data from the RisCoin cohort to investigate factors associated with a poor immune response to mRNA vaccination in these patients. Methods: From 4115 RisCoin participants, we matched 110 IBD patients by age and time interval since the second mRNA vaccination with 306 healthcare workers (HCW) without comorbidities (HCW-healthy) and 292 with medical conditions (HCW-plus); all were SARS-CoV-2 infection naïve. Basic questionnaires collected data on medication, COVID-19 vaccinations and side-effects, dietary patterns, lifestyle factors, and self-perceived stress. Main outcomes included anti-spike immunoglobulin levels and antibody-mediated live-virus neutralization immunity (NT) to the Omicron BA.1 variant (threshold NT ≥ 10 defined as IC50 values ≥1:10 serum dilution) after the second (baseline) and third vaccinations. Results: At baseline, IBD patients treated with anti-TNF but not those under vedolizumab or ustekinumab therapy had lower anti-spike levels compared to HCW-healthy and HCW-plus (166 versus 1384 and 1258 BAU/mL, respectively; p < 0.0001). Anti-TNF compared to vedolizumab/ustekinumab-treated patients reached NT titers above threshold in 17% versus 64%, respectively, and HCW-subgroups in 73% and 79% (all p < 0.0001). Current smokers showed a four to five times increased risk for non-neutralizing immunity compared to non-smokers. After the third vaccination, NT titers did not reach threshold in 15% anti-TNF compared to 5% vedolizumab/ustekinumab-treated patients and none of HCW (p < 0.01). Patients with IBD reported fewer clinical symptoms after vaccination. Perceived stress was not increased. Conclusions: Our findings support individualized schedules for mRNA-based vaccines in IBD patients with different immunosuppressive therapies and enforcement of non-smoking.

Keywords: SARS-CoV-2; anti-spike antibodies; perceived stress questionnaire; virus neutralizing immunity.

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Conflict of interest statement

L.K. reports consultant fees from Janssen-Cilag and Takeda and lecture honoraria from Falk Foundation outside the submitted work. TS received lecture honoraria from Nutricia and MSD, travel support from AbbVie and Ferring, and consulting fees from AstraZeneca outside the submitted work. H.P.T. reports consultant fees from AbbVie, Calypso Biotech, Immunic Janssen-Cilag, and Pharmacosmos and lecture honoraria from AbbVie, Biogen, BMS, Falk Foundation, Galapagos, Janssen-Cilag Pfizer, Pharmacosmos, and Takeda Pharma outside the submitted work. SK reports personal fees from AbbVie, AstraZeneca, Danone, Janssen, Mead Johnson, Nestle Nutrition, Pfizer, Sanofi, Takeda, and Tillotts outside the submitted work. All authors declare no conflicts of interest to this published work. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 4
Figure 4
Booster effect after the third vaccination on anti-spike levels (A,B) and neutralization titers (NT) (C,D) among adult IBD patients in total (A,C) and after stratification by type of IBD-medication (B,D) as well as in healthy HCW (HCW-healthy) and HCW with underlying diseases (HCW-plus).
Figure 1
Figure 1
Quantitative anti-spike antibody titers in adult patients with IBD as total cohort (A,C) and after stratification by type of IBD medication (B,D), healthy HCW (HCW-healthy) and HCW with underlying diseases (HCW-plus) at baseline (A,B) and follow-up (C,D).
Figure 2
Figure 2
Frequencies of non-neutralizing (NT ≥ 1:10 serum dilution) and neutralizing (<1:10 serum dilution) antibody titers among adult patients with IBD as total cohort (A,C) and after stratification by type of IBD-medication (B,D) compared to healthy HCW (HCW-healthy) and HCW with underlying diseases (HCW-plus) at baseline (A,B) and follow-up (C,D).
Figure 3
Figure 3
Factors associated with non-neutralizing antibody titers (NT ≥ 1:10 serum dilution) measured after second COVID-19 vaccination in adult patients with IBD using multivariable logistic regression.
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