Project description:BackgroundVaccination is a promising strategy to protect vulnerable groups like immunocompromised inflammatory bowel disease (IBD) patients from an infection with SARS-CoV-2. These patients may have lower immune responses. Little is known about the cellular and humoral immune response after a SARS-CoV-2 vaccination in IBD.Methods28 patients with IBD and 27 age- and sex-matched healthy controls were recruited at Jena University Hospital. Blood samples were taken before, after the first and in a subgroup of 11 patients after second dose of a SARS-CoV-2 vaccination. Cellular immune response including IFN-γ and TNF-α response and antibody titers were analyzed.ResultsOverall, 71.4% of the IBD-patients and 85.2% of the controls showed levels of anti-SARS-CoV-2 antibodies above the cutoff of 33.8 BAU/ml (p=0.329) after the first dose. Even in the absence of SARS-CoV-2 antibodies, IBD patients showed significant T cell responses after first SARS-CoV-2 vaccination compared to healthy controls, which was not influenced by different immunosuppressive regimens. Associated with the vaccination, we could also detect a slight increase of the TNF production among SARS-CoV-2-reactive TH cells in HD and IBD patients. After the second dose of vaccination, in IBD patients a further increase of humoral immune response in all but one patient was observed.ConclusionsAlready after the first dose of a SARS-CoV-2 vaccination, cellular immune response in IBD patients is comparable to controls, indicating a similar efficacy. However, close monitoring of long-term immunity in these patients should be considered.
Project description:Symptoms after SARS-CoV-2 primary vaccination among patients with inflammatory bowel disease (IBD) are generally of similar frequency, severity, and duration to those reported in the general population. The symptom profile after a 3 rd mRNA vaccine dose in the predominantly immune-compromised IBD population is unknown. We aimed to assess symptomology after a 3 rd or booster dose of mRNA vaccination in adults with IBD. We surveyed participants of the Coronavirus Risk Associations and Longitudinal Evaluation in IBD (CORALE-IBD) post-vaccination registry for symptom frequency and severity after a 3 rd mRNA vaccine dose in an observational cohort study. In total, 524 participants (70% female, mean age 45 years) reported a third dose of mRNA vaccination through October 11, 2021. Overall, 41% reported symptoms after a third dose, with symptoms generally more frequent and more severe among participants younger than 55 years. The most frequent postvaccination symptoms were injection site pain (39%), fatigue or malaise (34%), and headache (23%). These symptoms were all less frequently reported after dose 3 than after dose 2. Gastrointestinal symptoms were reported by 8.8%, which was slightly more frequent than after dose 2 (7.8%). Those with severe symptoms after dose 2 were more likely to have severe symptoms after dose 3. These findings can reassure the IBD patient and provider communities that the likelihood and distribution of symptoms after a third mRNA vaccine dose are generally similar to those after a second dose, and that the frequency of postvaccination symptoms after dose 3 are generally lower than after dose 2.
Project description:SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV-2 vaccination strategy in patients with IBD. The risks of SARS-CoV-2 vaccination are anticipated to be very low, and we strongly support SARS-CoV-2 vaccination in patients with IBD. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV-2 vaccination may be diminished in some patients with IBD, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in patients treated with anti-TNF drugs, are likely to outweigh these theoretical concerns. Key areas for further research are discussed, including vaccine hesitancy and its effect in the IBD community, the effect of immunosuppression on vaccine efficacy, and the search for predictive biomarkers of vaccine success.
Project description:BackgroundVaccination against SARS-CoV-2 is a highly effective strategy to protect against infection, which is predominantly mediated by vaccine-induced antibodies. Postvaccination antibodies are robustly produced by those with inflammatory bowel disease (IBD) even on immune-modifying therapies but are blunted by anti-TNF therapy. In contrast, T-cell response which primarily determines long-term efficacy against disease progression,, is less well understood. We aimed to assess the post-vaccination T-cell response and its relationship to antibody responses in patients with inflammatory bowel disease (IBD) on immune-modifying therapies.MethodsWe evaluated IBD patients who completed SARS-CoV-2 vaccination using samples collected at four time points (dose 1, dose 2, 2 weeks after dose 2, 8 weeks after dose 2). T-cell clonal analysis was performed by T-cell Receptor (TCR) immunosequencing. The breadth (number of unique sequences to a given protein) and depth (relative abundance of all the unique sequences to a given protein) of the T-cell clonal response were quantified using reference datasets and were compared to antibody responses.ResultsOverall, 303 subjects were included (55% female; 5% with prior COVID) (Table). 53% received BNT262b (Pfizer), 42% mRNA-1273 (Moderna) and 5% Ad26CoV2 (J&J). The Spike-specific clonal response peaked 2 weeks after completion of the vaccine regimen (3- and 5-fold for breadth and depth, respectively); no changes were seen for non-Spike clones, suggesting vaccine specificity. Reduced T-cell clonal depth was associated with chronologic age, male sex, and immunomodulator treatment. It was preserved by non-anti-TNF biologic therapies, and augmented clonal depth was associated with anti-TNF treatment. TCR depth and breadth were associated with vaccine type; after adjusting for age and gender, Ad26CoV2 (J&J) exhibited weaker metrics than mRNA-1273 (Moderna) (p=0.01 for each) or BNT262b (Pfizer) (p=0.056 for depth). Antibody and T-cell responses were only modestly correlated. While those with robust humoral responses also had robust TCR clonal expansion, a substantial fraction of patients with high antibody levels had only a minimal T-cell clonal response.ConclusionAge, sex and select immunotherapies are associated with the T-cell clonal response to SARS-CoV-2 vaccines, and T-cell responses are low in many patients despite high antibody levels. These factors, as well as differences seen by vaccine type may help guide reimmunization vaccine strategy in immune-impaired populations. Further study of the effects of anti-TNF therapy on vaccine responses are warranted.
Project description:BackgroundCharacterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.MethodsWe performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and high-throughput neutralization assay that incorporates SARS-CoV-2 spike protein onto a lentivirus and measures pseudoviral entry into ACE2-angiotensin converting enzyme 2 (ACE2) expressing human embryonic kidney 293 (HEK-293) cells was used.ResultsThere were 436 patients enrolled (mean age, 17 years, range 2-26 years; 58% male; 71% Crohn's disease, 29% ulcerative colitis, IBD-unspecified). Forty-four (10%) of enrolled subjects had SARS-CoV-2 S-RBD IgG antibodies. Compared to non-IBD adults (ambulatory) and hospitalized pediatric patients with PCR documented SARS-CoV-2 infection, S-RBD IgG antibody levels were significantly lower in the IBD cohort and by 6 months post infection most patients lacked neutralizing antibody. Following vaccination (n = 33), patients had a 15-fold higher S-RBD antibody response in comparison with natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2.ConclusionsThe lower and less durable SARS-CoV-2 S-RBD IgG response to natural infection in IBD patients receiving biologics puts them at risk of reinfection. The robust response to immunization is likely protective.
Project description:Patients with Crohn disease (CD) and ulcerative colitis (UC) suffer from chronic relapsing intestinal inflammation. While many studies focused on adaptive immunity, less is known about the role of innate immune cells in these diseases. Innate lymphoid cells (ILCs) are recently identified cells with a high cytokine-producing capacity at mucosal barriers. The aim was to study the impact of biological treatment on ILC in CD and UC. Patients initiating anti-tumor necrosis factor (TNF), ustekinumab, or vedolizumab treatment were prospectively followed up and peripheral and intestinal ILCs were determined. In the inflamed gut tissue of patients with inflammatory bowel disease, we found an increase of ILC1 and in immature NKp44- ILC3, whereas there was a decrease of mature NKp44+ ILC3 when compared to healthy controls (HCs). Similar but less pronounced changes in ILC1 were observed in blood, whereas circulating NKp44- ILC3 were decreased. Fifteen percent of CD patients had NKp44+ ILC3 in blood and these cells were not detected in blood of HCs or UC patients. Therapy with three different biologicals (ustekinumab targeting the IL-12/23 cytokines, anti-TNF and vedolizumab) partly restored intestinal ILC subset equilibrium with a decrease of ILC1 (except for ustekinumab) and an increase of NKp44+ ILC3. Anti-TNF also mobilized more NKp44+ ILC3 in circulation. As ILC1 are proinflammatory cells and as NKp44+ ILC3 contribute to homeostasis of intestinal mucosa, the observed effects of biologicals on ILCs might contribute to their clinical efficacy.
Project description:Patients with inflammatory bowel disease (IBD) do not receive routine preventive care at the same rate as the general population. IBD places patients at increased risk for developing vaccine-preventable illnesses. This risk is further exacerbated by immunosuppressive therapy. This article highlights the necessary vaccinations for IBD patients and the timing of vaccination for immunosuppressed patients, and discusses the health maintenance needs and preventive care issues related to heart disease, smoking, osteoporosis, mental health, cervical cancer, and skin cancer.
Project description:BACKGROUND:The use and value of different complementary therapies requires investigation. In particular, qualitative research is required to understand the perceptions and experiences of patients who undergo healing therapy as one type of complementary therapy. The aim of this research is to consider patients perceptions and experiences following a course of healing therapy. METHODS:Twenty two patients took part in this study. This included 13 patients with irritable bowel disease (3 male, 10 female, 47.6?±?15.0 years), 6 patients with ulcerative colitis (3 male, 3 female, 48.5?±?25.6 years) and 3 female patients with Crohn's Disease (45.0?±?5.2 years). Each patient undertook a single semi-structured interview following a course of healing therapy. The data was analysed using a thematic analysis. RESULTS:Three broad themes were identified from patient interviews (1) The understanding and expectation of healing (2) Experiences and reflection on healing (3) Impact and outcome of healing. The details of each theme are explored within the text, often revealing a unique experience of healing therapy. CONCLUSION:Patients were open towards the benefits that could be attained by healing, although most patients were not sure what healing would entail. Some patients expected to be relaxed by the sessions. However, the most consistent reports were that patients experienced a relaxing sensation that was generated within the session and lasted for a time period after the sessions. In addition to this the healing appeared to be associated with patients feeling more tolerant of their symptoms. Patients valued the therapist and their input into the healing process. It should be noted however, that this report cannot consider the efficacy of the treatment. Further details and experiences are considered within the article, including one negative experience.