Su1485: COVID-19 VACCINE-INDUCED ANTIBODY RESPONSES ARE IMPAIRED IN IBD PATIENTS TREATED WITH INFLIXIMAB, USTEKINUMAB OR TOFACITINIB, BUT NOT THIOPURINES OR VEDOLIZUMAB

Alexander, James L.; Kennedy, Nicholas A; Ibraheim, Hajir; Anandabaskaran, Sulak; Saifuddin, Aamir; Seoane, R.; Liu, Zhigang; Nice, Rachel; Bewshea, Claire; D’Mello, Andrea; Constable, Laura E.; Jones, G. R.; Balarajah, Sharmili; Fiorentino, Francesca; Sebastian, Shaji; Irving, Peter M.; Hicks, Lucy; Williams, Horace R T; Kent, Alexandra; Parkes, Miles; Kok, Klaartje; Segal, Jonathan; Altmann, Daniel M.; Boyton, Rosemary J.; Goodhand, James; Hart, Ailsa; Lees, Charlie W.; Ahmad, Tariq; Powell, Nick

doi:10.1016/s0016-5085(22)61407-0

Cited by 4 publications

(6 citation statements)

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“…Thus, we may have underestimated the number of pauci-symptomatic infections if they were contracted early during the follow-up, particularly for patients treated with anti-TNF, that can attenuate seroprevalence as suggested in some studies (43,44), even though another study recently showed that patients with IBD previously infected with COVID-19 have similar quantitative antibody response as healthy controls previously infected with COVID-19 (45). The parallel can be drawn with the response to the vaccination because the antibody levels after vaccination have been shown to be lower with anti-TNF agents than with other treatments, studied in this prospective casecontrol study (483 cases for 121 controls) between May and November 2021, in which the antibody level measured between 53 and 92 days after the second vaccination dose was lower under infliximab (geometric mean ratio 0.12, 95% CI 0.08-0.17; p<0.0001), compared to thiopurines (0.89, 0.64-1.24; p=0.50), ustekinumab (0.69, 0.41-1.19; p=0.18), or vedolizumab (1.16, 0.74-1.83; p=0.51) (32). These attenuated serological responses still exist after a third dose of an mRNA-based vaccine in infliximab-but not in vedolizumab-treated patients, as demonstrated recently in an analysis of the CLARITY IBD study (46).…”

Section: Discussionmentioning

confidence: 96%

“…Moreover, nowadays, vaccine safety and efficacy is a key question in the context of patients who have biological therapy, especially when seeing the rate of COVID-19 vaccine hesitancy in IBD patients (28,29). Serologic response is good after vaccination in patients with IBD (30, 31), although lower with anti-TNF agents than with other treatments including vedolizumab (32). Real-word data have also proven the safety of COVID-19 vaccines in IBD patients (33,34).…”

Section: Introductionmentioning

confidence: 99%

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The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics

Lelong,

Josien,

Coste-Burel

et al. 2023

Front. Immunol.

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BackgroundPatients with inflammatory bowel disease (IBD) may have a modified immune response to SARS-CoV-2. The objectives were to evaluate the prevalence of COVID-19 in patients treated with infliximab or vedolizumab, to analyze the factors associated with the infection, the impact of treatments and trough levels.MethodsPatients with IBD treated with intravenous biologics in 14 French centers were included between March and June 2020 and followed-up for 6 months. Blood samples were collected for serologies and trough levels. The analysis of factors associated with COVID-19 was conducted in a matched 1:1 case-control sub-study with positive patients.ResultsIn total, 1026 patients were included (74.9% infliximab). Over the follow-up period, 420 patients reported the occurrence of COVID-19 symptoms; 342 had been tested of whom 18 were positive. At the end of follow-up, 38 patients had a positive serology. Considering both nasal tests and serologies together, 46 patients (4.5%) had been infected. The risk of COVID-19 was related neither to the use of treatments (whatever the trough levels) nor to disease activity. Infections were more frequent when using public transport or living in flats in urban areas.ConclusionsThe prevalence rate of COVID-19 in this IBD population treated with intravenous infliximab or vedolizumab was the same as the one in the French population before the start of the vaccination campaign. The risk was increased by urban living and was not influenced by disease activity or biologics. Sanitary barrier measures remain the best way to protect against SARS-CoV-2 in patients with IBD in biological therapy.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics

Lelong,

Josien,

Coste-Burel

et al. 2023

Front. Immunol.

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show abstract

“…Vaccine effectiveness against viral acquisition and severe outcomes was assessed in recent population-based studies during Omicron outbreaks, suggesting that a booster dose of COVID-19 vaccine is needed for older patients and high-risk populations against severe or fatal outcomes (25). Bivalent booster vaccines are now encouraged among IBD patients taking TNF antagonists and tofacitinib based on emerging evidence regarding the effectiveness of COVID-19 vaccines (8,26). No significant difference in vaccination doses was observed between the infection and non-infection group or between the mild and moderate groups in this study despite the same infection-naïve background.…”

Section: Discussionmentioning

confidence: 99%

Impact of the first wave of COVID-19 on Crohn’s disease after the end of “zero-COVID” policy in China

Hu,

Li,

Yan

et al. 2023

Front. Public Health

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BackgroundThe incidence and severity of coronavirus disease 2019 (COVID-19) among Crohn’s disease (CD) patients are unknown in China. This study aimed to clarify the clinical courses and outcomes of CD patients in the first COVID-19 wave after the end of “zero-COVID” policy in China.MethodsClinical characteristics, including vaccination doses and medications of 880 CD patients from a prospective cohort were collected for analysis.ResultsOf the enrolled patients (n = 880) who underwent nucleic acid or antigen testing for COVID-19 from Dec 7, 2022, to Jan 7, 2023, 779 (88.5%) were infected with COVID-19. Among the infected patients, 755 (96.9%) were mild, 14 (1.8%) were moderate, one patient with leukemia died of cerebral hemorrhage (mortality, 0.1%) and only 9 (1.2%) were asymptomatic. Fever, cough, headache and appetite loss were the most frequently observed symptoms in general, respiratory, neurological and gastrointestinal manifestations, respectively. The age and disease duration were significantly higher (40/32, 5.6/3.6, all p < 0.05) in moderate patients than those in mild patients. All other clinical characteristics, including CD activity and medication exposure, showed no significant differences between the above two groups. Furthermore, no significant difference in vaccination or comorbidities was observed between the two groups.ConclusionMost CD patients contracted the Omicron infection and experienced mild disease courses in the first COVID-19 wave attack after China ended the “zero-COVID” policy irrespective of vaccination dose or comorbidities.

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“…It is important to notice that TNF inhibitor treatment causes a lower serologic response and impaired memory B cell differentiation due to the repeated mRNA SARS-CoV-2 vaccination. In fact, patients undergoing anti-TNF treatment for chronic inflammatory disease showed a significantly lower humoral response after the SARS-CoV-2 mRNA vaccine (68). After two doses of the mRNA-based BNT162b2 vaccine, these patients showed defects in the formation of antibody (Ab)-secreting B cells, affinity-matured memory B cells, and a dramatic reduction in Ab longevity (68)(69)(70)(71)(72)(73).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profile of TNFhigh MAIT cells is linked to B cell response following SARS-CoV-2 vaccination

et al. 2023

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IntroductionHigher frequencies of mucosal-associated invariant T (MAIT) cells were associated with an increased adaptive response to mRNA BNT162b2 SARS-CoV-2 vaccine, however, the mechanistic insights into this relationship are unknown. In the present study, we hypothesized that the TNF response of MAIT cells supports B cell activation following SARS-CoV-2 immunization.MethodsTo investigate the effects of repeated SARS-CoV-2 vaccinations on the peripheral blood mononuclear cells (PBMCs), we performed a longitudinal single cell (sc)RNA-seq and scTCR-seq analysis of SARS-CoV-2 vaccinated healthy adults with two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Collection of PBMCs was performed 1 day before, 3 and 17 days after prime vaccination, and 3 days and 3 months following vaccine boost. Based on scRNA/TCR-seq data related to regulatory signals induced by the vaccine, we used computational approaches for the functional pathway enrichment analysis (Reactome), dynamics of the effector cell-polarization (RNA Velocity and CellRank), and cell-cell communication (NicheNet).ResultsWe identified MAIT cells as an important source of TNF across circulating lymphocytes in response to repeated SARS-CoV-2 BNT162b2 vaccination. The TNFhigh signature of MAIT cells was induced by the second administration of the vaccine. Notably, the increased TNF expression was associated with MAIT cell proliferation and efficient anti-SARS-CoV-2 antibody production. Finally, by decoding the ligand-receptor interactions and incorporating intracellular signaling, we predicted TNFhigh MAIT cell interplay with different B cell subsets. In specific, predicted TNF-mediated activation was selectively directed to conventional switched memory B cells, which are deputed to high-affinity long-term memory.DiscussionOverall, our results indicate that SARS-CoV-2 BNT162b2 vaccination influences MAIT cell frequencies and their transcriptional effector profile with the potential to promote B cell activation. This research also provides a blueprint for the promising use of MAIT cells as cellular adjuvants in mRNA-based vaccines.

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Su1485: COVID-19 VACCINE-INDUCED ANTIBODY RESPONSES ARE IMPAIRED IN IBD PATIENTS TREATED WITH INFLIXIMAB, USTEKINUMAB OR TOFACITINIB, BUT NOT THIOPURINES OR VEDOLIZUMAB

Cited by 4 publications

References 0 publications

The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics

The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics

Impact of the first wave of COVID-19 on Crohn’s disease after the end of “zero-COVID” policy in China

Transcriptomic profile of TNFhigh MAIT cells is linked to B cell response following SARS-CoV-2 vaccination

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