Higher and Sustained Cell-Mediated Immune Responses After 3 Doses of mRNA COVID-19 Vaccine in Patients With Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy

INTRODUCTION: Studies suggest that the generation of durable T-cell immunity following coronavirus disease 2019 (COVID-19) vaccination protects against severe disease. The aim of this study was to measure cell-mediated immune response (CMIR) 1-2 months and 6 months after a third dose of a COVID-19 mRNA vaccine. METHODS: This prospective study (HumoRal and CellULar initial and Sustained immunogenicity in patients with inflammatory bowel disease [IBD]) evaluated CMIR at 28-65 days (t(1)) after dose 2, 28-65 days (t(2)) (n = 183) and 6 months (+/- 45 days) (t(3)) (n = 167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood sample available 28-65 days (t(4)) (n = 55) after a fourth dose. Primary outcomes were CMIR at (t(2)) and (t(3)). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t(4)). RESULTS: All patients had measurable CMIR at all time points. CMIR increased at t(2) compared with that at t(1) (median 1,467 responding cells per million (interquartile range [IQR] 410-5,971) vs 313 (94-960) P < 0.001). There was no significant waning in t(2) vs t(3) or significant boosting at t(4). Those on anti-tumor necrosis factor monotherapy had a higher CMIR compared with those not on this therapy at t(2) (4,132 [IQR 1,136-8,795] vs 869 [IQR 343-3,221] P < 0.001) and t(3) (2,843 [IQR 596-6,459] vs 654 [IQR 143-2,067] P < 0.001). In univariable analysis, anti-tumor necrosis factor monotherapy was associated with a higher CMIR at t(2) (P < 0.001) and t(3) (P < 0.001) and confirmed in a multivariable model (P < 0.001). DISCUSSION: A third dose of a COVID-19 vaccine boosts CMIR, and the response is sustained in patients with IBD.