key: cord-0687049-3xaid8xi authors: Doherty, Jayne; Fennessy, Sean; Stack, Roisin; O’ Morain, Neil; Cullen, Garret; Ryan, Elizabeth J.; De Gascun, Cillian; Doherty, Glen A. title: Review Article: vaccination for patients with inflammatory bowel disease during the COVID‐19 pandemic date: 2021-09-02 journal: Aliment Pharmacol Ther DOI: 10.1111/apt.16590 sha: f58ee4028c4d9d8cc4ce876c016c30e8399277e1 doc_id: 687049 cord_uid: 3xaid8xi BACKGROUND: Poor immune responses are frequently observed in patients with inflammatory bowel disease (IBD) receiving established vaccines; risk factors include immunosuppressants and active disease. AIMS: To summarise available information regarding immune responses achieved in patients with IBD receiving established vaccines. Using this information, to identify risk factors in the IBD population related to poor vaccine‐induced immunity that may be applicable to vaccines against COVID‐19. METHODS: We undertook a literature review on immunity to currently recommended vaccines for patients with IBD and to COVID‐19 vaccines and summarised the relevant literature. RESULTS: Patients with IBD have reduced immune responses following vaccination compared to the general population. Factors including the use of immunomodulators and anti‐TNF agents reduce response rates. Patients with IBD should be vaccinated against COVID‐19 at the earliest opportunity as recommended by International Advisory Committees, and vaccination should not be deferred because a patient is receiving immune‐modifying therapies. Antibody titres to COVID‐19 vaccines appear to be reduced in patients receiving anti‐TNF therapy, especially in combination with immunomodulators after one vaccination. Therefore, we should optimise any established risk factors that could impact response to vaccination in patients with IBD before vaccination. CONCLUSIONS: Ideally, patients with IBD should be vaccinated at the earliest opportunity against COVID‐19. Patients should be in remission and, if possible, have their corticosteroid dose minimised before vaccination. Further research is required to determine the impact of different biologics on vaccine response to COVID‐19 and the potential for booster vaccines or heterologous prime‐boost vaccinations in the IBD population. A novel coronavirus referred to as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 21) was identified in late 2019 as the causative agent of a respiratory syndrome named coronavirus disease and has subsequently resulted in a worldwide pandemic. As of summer 2021, COVID-19 has been confirmed in 184 324 026 people worldwide and has resulted in 3 992 680 deaths. 1 deaths. 3 From cases reported to SECURE-IBD 15% of patients with IBD have been hospitalised and 3% have required ICU admission. 3 A recent meta-analysis found that reassuringly the risk of contracting severe COVID-19 in patients with IBD is not higher than the general population and the use of biologics may be associated with better outcomes for patients who contract Managing the risks of COVID-19 in patients with IBD has been the subject of much effort. Given the development of numerous vaccines against COVID-19, attention has turned to the role of vaccination as a key tool to manage the risks associated with COVID-19. Effective vaccines generate an immune response that mimics that induced by natural infection. Vaccinated individuals can produce large quantities of high-affinity antibodies or effector T cells quickly, thus protecting them from severe disease if subsequently exposed to the pathogen. Vaccine-induced protective immune responses are especially important in vulnerable cohorts especially those considered immunocompromised which include a sub-cohort of patients with IBD. There is evidence that patients with IBD remain at significant risk of vaccine-preventable infections, suggesting vaccines confer suboptimal protection in this cohort. 5, 6 Several vaccines against COVID-19 have recently been approved for use and are being deployed in widespread immunisation programmes. In this review article, we aim to address several key questions which will help inform our approach to COVID-19 vaccination in patients with IBD. Firstly, we will discuss whether patients with IBD show altered vaccine responses and which disease characteristics contribute to modulating vaccine-induced immunity. Secondly, we will review what can be learnt from the existing data on the impact of IBD therapies on response to vaccination by focusing on a number of established anti-viral vaccines. Finally, we will examine how this informs our approach to the delivery of the current and upcoming COVID-19 vaccines to maximise their impact in the IBD community. A comprehensive literature search was conducted for relevant literature (published articles and abstracts) by performing a systematic search of two databases: PubMed and Cochrane Library CENTRAL. No restrictions were applied to language or publication date. Keywords used were "inflammatory bowel disease" or "crohn's disease" or "ulcerative colitis" and/or "vaccine response" or "Influenza" or "Hepatitis B" or "Varicella" or "COVID-19 vaccination" or "vaccine uptake." Current European and American guidelines on current vaccinations in patients with IBD and guidelines on vaccination against COVID-19 infection were also reviewed. Eligible articles were reviewed and the quality was assessed by two independent reviewers. Studies pertaining to or referencing the following topics were eligible for inclusion: (a) vaccine uptake in patients with IBD; (b) differences in the innate and adaptive immunity in patients with IBD; (c) vaccine response rates in patients with IBD; (d) COVID-19 vaccines; (e) response rates to COVID-19 vaccines in the IBD community. Case series or case reports were excluded due to high risk of publication bias. Studies that reported insufficient data on the outcomes of interest were also excluded. IBD is characterised by chronic inflammation arising from an abnormal host immune response to dietary and microbial antigens. The pathogenesis of both Crohn's disease (CD) and ulcerative colitis (UC) is complex and is thought to be secondary to the interplay between genetic susceptibility, environmental factors and an altered gut microbiota leading to aberrant innate and adaptive immune responses. 7, 8 Multiple immune pathways are dysregulated in both CD and UC. 7, 8 There have been several reports suggesting IBD may arise from a fundamentally inadequate rather than excessive gut immune response with one study showing a defective neutrophil recruitment and bacterial clearance in patients with CD. 9 There is a body of evidence highlighting immune-system dysfunction in patients with IBD. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are pathogen recognition receptors (PRRs) that alert the innate immune system to the presence of microbes by detecting conserved molecular patterns (eg bacterial lipopolysaccharide or viral nucleic acids). Ligation of TLRs/NLRs triggers innate immune responses and pro-inflammatory cytokine production that drives the subsequent adaptive immune response. PRRs play a critical role in maintaining gut homeostasis, controlling immune responses along with shaping the microbiota. Patients with IBD exhibit differential expression of TLRs in comparison to healthy controls. 10 Mutations in NLRs have been identified in CD, with NOD2 mutations the most common mutation. 11 Vaccine formulations contain adjuvants that activate innate immunity via PRRs resulting in local inflammation at the injection site. Antigen-presenting cells (APCs) traffic to the site of injection in response to these inflammatory signals and are enabled to process and present antigens and prime both the humoral and cellular arms of the adaptive immune response (Figure 1) . Thus, the inherent defects in microbial sensing that underpin IBD pathogenesis may also impact a patient's response to vaccination. Dendritic cells (DC) are an important population of APCs expressing high levels of PRRs. They respond to microbial signals, traffic to local lymph nodes where they process and present antigens to naïve T-cells. Once in the lymph node, they upregulate co-stimulatory molecules such as CD40/CD80/CD86 and secrete cytokines such as IL-12 that are required for T-cell polarisation. The plasmacytoid DC subset plays an important role in anti-viral immunity as they are a potent source of type I Interferon (IFN). 12 Thus, DCs are key mediators of response to vaccination. Patients with IBD have significantly lower levels of circulating DC during disease flares compared to healthy controls. 11 Even patients with the inactive disease have shown reduced frequencies of circulating DC. 13 A significantly higher frequency of plasmacytoid DC in the inflamed colonic mucosa and mesenteric lymph nodes of IBD patients compared to healthy controls has also been reported. 14 It appears that in IBD especially when the disease is active, DC migrate from the bloodstream to the gut. Macrophages are another population of APCs critical in the initiation of vaccine-induced immunity and protection against viral infection. Macrophages have the ability to destroy virally infected cells and produce IFN. However, these effects are evident only if the virus is destroyed or contained by macrophages. If a virus replicates in macrophages, the infected macrophages may aid viral transmission. The permissiveness of macrophages for viral replication depends on factors including the age and host genetics. 15 In CD, macrophages are compromised and produce subnormal amounts of pro-inflammatory cytokines. 16 Whether these defects in DC, macrophages and PRRs in patients with IBD could impact systemic immunogenicity and aspects such as a patient's response to vaccination is still unknown. One recent review of 14 590 patients with IBD reported an elevated risk of opportunistic infections (OI) but no increased risk was evident for patients on biologic therapy. 17 This observation supports the hypothesis that an immune-system dysfunction in these patients may contribute to poorer vaccine response. Despite the indirect evidence outlined above, it remains the case that there is little direct evidence that patients with IBD, even if experiencing active disease, should be considered significantly immunosuppressed and therefore less likely to respond to vaccination. The statement from the ECCO guidelines on OI in IBD still, therefore, remains broadly true when it states "Patients with IBD should not be routinely considered to have altered immunocompetence." 5 This topic should, however, remain a focus for investigation and efforts made to evaluate whether patients with IBD, not receiving systemic immunosuppressive therapies show any difference in the degree in initial response and durability of response to COVID-19 vaccination. Expert recommendations promoting the efficacy and safety of vaccinations are widespread in the IBD literature. 5, [18] [19] [20] Both ECCO and BSG guidelines advocate screening for OI and vaccinating where possible, prior to commencing immunomodulatory therapy. 5, 18 Given 80% of patients will require corticosteroids, 40% thiopurines and 20% anti-TNF therapy over their disease course, 5 From the patient's perspective, lack of awareness (49%) and fear of side effects (18%) are the most common reasons for not having the influenza vaccine. 6 Uptake of the COVID-19 vaccine worldwide has been promising. Several studies have looked at attitudes to COVID-19 vaccine uptake and reasons for vaccine hesitancy but none to date specifically in the IBD community. One study of 1000 people online in Ireland and the UK revealed 75% of participants intend to get a COVID-19 vaccine, 11% said they would not be vaccinated and 14% were unsure regarding vaccination. Women and younger people were significantly less likely to report an intention to avail of a COVID-19 vaccine. The survey revealed that peer influences are strongly associated with young women's intentions on vaccination. 27 A separate polish study questioned 1427 people on COVID-19 vaccine uptake. Interesting predictors for acceptance of the vaccination included being talked through the importance of vaccination and potential side-effects by a medical professional and suffering from chronic illnesses. Those who opted not to be vaccinated were most frequently concerned about the vaccine efficacy or side-effects. 28 Both these studies highlight the importance and need for members of the IBD multidisciplinary team to inform and counsel our patients to ensure optimal uptake of COVID-19 vaccines. Involvement of patient organisations is also necessary with clear and concise patient information available which clinicians can refer their patients to. 29 Immunosuppressive treatment is a significant driver of the increased susceptibility to infection observed in patients with IBD. 5 One recent study reported a threefold increase of serious systemic viral infections in patients with IBD compared to the general population. The main risk factors for contracting infection were clinically active Approximately 300 000-650 000 people die worldwide from influenza each year. 31 The risk of contracting influenza and requiring hospitalisation is significantly greater in the IBD population, 32 therefore, yearly influenza vaccination is recommended. 5, 18, 19 The influenza vaccine comes in two forms, an inactivated vaccine and a live vaccine. The live vaccine is not recommended for use in immunocompromised patients. 5, 18, 19 Guidelines do not advise whether immunocompromised patients should receive standard dosage (SD) or high dosage (HD) of the trivalent inactivated influenza vaccine. One systematic review highlighted the fact that patients who received a HD vaccination had increased rates of seroconversion compared to those who received the SD in both immunocompromised individuals and adults aged 50-64 years. 33 The emergence of the novel influenza A (H1N1) virus in 2009 stimulated research activity in the field of influenza vaccination. In the general population, serological protection rates of greater than 85% were reported with the H1N1 influenza vaccine. 34, 35 However, rates of serological protection to influenza in patients with IBD tend to differ depending on treatment strategies. One study found influenza vaccine yielded high seroprotection rates in patients with IBD, however, patients receiving anti-TNF treatment had lower rates of persistent seroprotection at 6 months post-vaccination. 36 Cullen et al found serological protection rates against the H1N1 influenza vaccine in the IBD community was much less than that of the general population at only 50%. 37 Levels of seroprotection were significantly lower in patients receiving immunosuppression (glucocorticoids, immunomodulators or biologic treatments) compared with patients not on these drugs (44% versus 64%). 37 A prospective randomised control trial (RCT) examined serologic response to the inactivated trivalent influenza vaccine in patients receiving infliximab (IFX) and found despite patients mounting an initial immune response to vaccination, response rates ranged between 25% and 40%. 38 Interestingly, vaccine administration at the time of infusion, or between infusions, did not impact response. 38 Furthermore, a 2018 Japanese study assessed the immunogenicity of the quadrivalent influenza vaccine for patients with IBD on immunosuppression and found patients receiving IFX had lower seroprotection rates than those on 5-ASA or azathioprine. 39 The addition of a booster vaccine does not appear to improve response rates in patients with IBD. 39, 40 However, the HD quadrivalent influenza vaccine seems to improve immunogenicity in patients on immunosuppressive therapy. 41, 42 One RCT found patients with IBD on anti-TNF monotherapy receiving the HD influenza vaccine had significantly higher post-immunisation antibody levels compared with SD vaccine, 41 with similar results seen in patients with rheumatoid arthritis on immunosuppressants. 42 Overall, the inactivated influenza vaccine is safe to administer to patients with IBD, including patients on immunosuppressants with no association with increased IBD activity. 43, 44 Patients on immunosuppressants have reduced seroconversion rates compared to the general population. The ideal time to vaccinate patients is prior to starting immunosuppressive therapy where possible, to improve response rates. It is unclear whether patients on immunosuppressants would have higher response rates and be better protected with the HD vaccination protocol and this could be an area for further research if similar response rates are seen with the COVID-19 vaccines. The prevalence of HBV infection varies throughout the world, with <1% of the population of Northern Europe being infected. 45 ECCO and BSG guidelines recommend all patients should be screened for HBV at diagnosis of IBD to help expedite necessary vaccinations and reduce delays initiating therapy. 5, 18 In the healthy, general population 10% of HBV vaccine recipients fail to mount an adequate antibody response. 46 Andrade et al 47 found patients receiving IFX, azathioprine or combination therapy had lower anti-HBsAg levels indicating an inadequate vaccine response. A 2017 meta-analysis found response rate to the HBV vaccine in patients with IBD, regardless of therapy was 61% 48 compared to 90% in the general population. 46 Younger patients and those F I G U R E 1 Impact of having IBD and IBD medications on the immune response to COVID-19 vaccines. A, Innate immune priming: IBD is associated with SNPs in genes regulating the innate immune response (eg innate immune sensors such as TLRs), therefore tissue resident antigen presenting cells (eg DCs) in patients with IBD may respond differently to the vaccines. Inflammatory cytokines produced in response to the vaccines may be blunted by anti-inflammatory medications (eg corticosteroids or biologic agents such as anti-TNF). B, Antigen presentation: Mature DC migrate to the local LN where they present antigen to naïve CD4/CD8+ T and B lymphocytes, providing co-stimulation and driving polarisation by secreting cytokines. IBD medications can limit antigen presentation. C, T cell proliferation and polarisation: Patients with CD tend to have immune responses polarised towards inflammatory Th1/Th17 cells, while patients with UC have a bias towards Th2 cells. D, CD4+ T cell: B cell interaction: Antigen specific CD4+ T cells interact with B cells providing co-stimulation via CD40:CD40L interaction to drive B cell proliferation, affinity maturation and class switch recombination. T cell-derived cytokines (eg IL-4) are key to determining the antibody isotype and function. E, Immune Memory: Antigen-specific T and B cell clones expanded due to vaccination should give rise to long-lived memory cells. Patients with IBD frequently display an exhausted T cell phenotype (due to constant immune activation) and this may impact the phenotype and function of immune memory cells. Image created by BioRender.com. vaccinated during remission had higher response rates. Use of immunosuppressive agents was associated with reduced rates of immunogenicity (Table 1) . 48 Loras et al 49 found seroconversion rates against Hepatitis B were only 44% in adults with IBD on anti-TNF therapy (Table 1) . A second metanalysis evaluated the efficacy of the HBV vaccine in patients with IBD and found patients with IBD were significantly less likely to respond to the HBV vaccination compared with healthy controls. Overall, the pooled proportion of adequate response to the Hepatitis B vaccine in patients with IBD was 61% and the odds ratio of HBV response in patients with IBD was 0.13 (95% confidence interval 0.05-0.33, P = 0.001). 50 Patients with IBD on immunosuppressants had significantly lower serological response rates to the HBV vaccine compared to the general population. 50 The standard HBV vaccination of three doses is given at 0, 1 and 6 months with an accelerated schedule for "rapid protection" with dosing at 0, 1, 2 and 12 months. 51 A randomised prospective study found patients with IBD had a significantly higher response rate to the accelerated dosing schedule compared to standard dosing (75% vs 41%) ( Table 2 ). 52 A recent RCT from Chaparro et al found a 4-dose schedule was more effective than a 3-dose regimen with significantly higher response rates for Hepatitis B vaccination in patients with IBD. As seen in other studies older age and treatment with immunomodulators or anti-TNFs impaired response to vaccination. 53 ECCO guidelines recommend all IBD patients receive an accelerated vaccination schedule using a double-dose protocol, whilst the ACG guidelines recommend the standard vaccination schedule. 5, 19 Once further data are available on response rates in patients with IBD to the COVID-19 vaccines the use of accelerated or double-dose vaccine schedules for sub-cohorts of patient with IBD that have impaired response to the vaccine may be an option. Varicella-zoster virus (VZV) causes chickenpox and herpes zoster (shingles). In most European countries there is close to universal VZV seroconversion by late childhood. 54 Primary VZV infection is more severe in adults than children. 55 Patients with IBD on immunosuppression appear to be at increased risk of complications with primary varicella infection. 56, 57 A retrospective review of 20 patients with IBD on immunosuppression found a 20% mortality from primary VZV infection, with three of these patients on corticosteroids at the time of infection. 58 A separate retrospective study found a strong association with the requirement of hospitalisation for primary VZV and IBD in a paediatric cohort. 59 Given the high risk of complications with primary varicella infection in patients with IBD, the ACG and ECCO recommend screening for prior exposure to varicella in all patients with IBD and vaccination if naïve. 5, 19 The varicella vaccine is a live vaccine, therefore, cannot be given to patients receiving immunosuppressants. Both ECCO and the ACG recommends vaccination at least 3-4weeks prior to commencing immunosuppressants. 5, 19 In a systematic review of 40 observational studies in patients with immune-mediated disorders (IBD n = 20 556) investigators found although seroconversion following the varicella vaccine was high, it was reduced by immunosuppressive therapies. 60 Vaccines against SARS-CoV-2 that elicit protective immune re- in the control group. 67 In this study overall vaccine efficacy was 70% which was statistically significant compared to placebo. No serious safety events related to the vaccine were reported. 67 The vaccine generated similarly robust immune responses against the SARS-CoV-2 virus across all age groups. 67 vaccine. 84 It is thought this anaphylaxis may be due to polyethylene glycol that has been included in vaccine formulation as a stabiliser. 84 The FDA has advised individuals with severe allergic reactions to vaccines or ingredients in the vaccine should avoid this vaccine. 85 The UK MHRA advised individuals with a history of anaphylaxis to medicine or food not to receive the vaccine. 86 A second mRNA vaccine, the Moderna vaccine, completed a phase three trial called the COVE trial after promising results from phase 1/2 clinical trials. 87 Positive results from the phase 3 trial showed a vaccine efficacy against COVID-19 of 94% and vaccine efficacy against severe COVID-19 was 100%. 88 In this study, 7000 participants were over the age of 65 and over 5000 participants under the age of 65 had high-risk chronic diseases. In total 42% of participants were defined as a medically high-risk group. 88 One hundred and ninety-six cases of COVID-19 occurred, of which 30 cases were severe. All 30 cases occurred in the placebo group and none in the vaccinated group. 88 No serious safety concerns have been identified to date. The most common adverse reactions reported include injection site pain, fatigue, myalgia, arthralgia, headache, and erythema at the injection site. 88 EUA of this vaccine by the EMA has been granted. In addition to these leading vaccines, numerous other potential COVID-19 vaccines are in phase 3 clinical trial at present. 89 A summary of potential vaccines is summarised in Table 3 with the AstraZeneca vaccine. 98 In the event that current vaccines prove to be less effective against one or more variants, it will be pos- Overall, to date we can be guided by advice provided by the International Organisation for the Study of Inflammatory Bowel Disease and the COVID-19 ECCO taskforce both of which advise patients with IBD should be vaccinated against SARS-CoV-2 at the earliest opportunity possible and vaccination should not be deferred because a patient with IBD is receiving immune-modifying therapies. [103] [104] [105] Although data are minimal, the ECCO Taskforce cautiously recommends to use the mRNA vaccine to vaccinate IBD patients on immunomodulatory medication since the vaccine's efficacy to protect against the mild and severe disease was shown to be higher for mRNA vaccines (94%-95%) compared to the viral vectorvaccines, where the mild disease still occurs in about 30%-40% of the vaccinated persons. 104 From observations related to the use of established vaccines in patients with IBD, we can conclude that patients with IBD tend to have poorer vaccine-induced immunity than the general population. The use of immunosuppressants and disease activity are both implicated in causing lower rates of seroconversion. For certain vaccines including the hepatitis B vaccine and influenza vaccines accelerated protocolls and higher dosing have shown potential to improve the immunity achieved for patient with IBD. To date, data are limited in the IBD population on response rates to the COVID-19 vaccine but similar issues seem to be arising as seen with established vaccines. There is clearly a requirement for large scale collaborative research efforts to gather larger datasets on the response rates to different vaccines amongst patients with IBD and examine the impact of both disease activity and different IBD therapies on the immunity generated by vaccination. It is recommended all patients with IBD can be vaccinated against COVID-19 with the currently available vaccines. To improve immunogenicity, it seems prudent to take a few elementary precautions prior to patients being vaccinated; patients should ideally be in disease remission and if possible, corticosteroids doses should be minimised. Preferably, the vaccination should be given prior to newly commencing potentially immunosuppressant medications where possible (though IBD treatments should not be unduly delayed to allow vaccination). Research into the benefits of double dose vaccines, additional booster dosing or use of heterologous prime-boost vaccination schedules for immunosuppressed patients' needs to be considered. Finally, the potential for short drug holidays (with oral agents), vaccination at the trough level for biologic agents or antibody testing in vulnerable cohorts may be an area that would benefit from prospective evaluation. Declaration of personal interest: None. Guarantor of the article: Jayne Doherty. Author contributors: Authors contributions as submitted on original submission are correct. No funding was required for this review article. All authors have reviewed and approve the final version of this paper. Data sharing is not applicable to this article as no new data were created or analyzed in this study. https://orcid.org/0000-0002-1599-1447 Neil O' Morain https://orcid.org/0000-0003-2542-9455 COVID-19) -World Health Organization. World Health Organisation Centres for Disease Control and Prevention SECURE-IBD Database Public Data Update Risk and outcomes of coronavirus disease in patients with inflammatory bowel disease: a systematic review and meta-analysis. United Second European evidencebased consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease Patients with inflammatory bowel disease are at risk for vaccine-preventable illnesses Crohn's disease Defective acute inflammation in Crohn's disease: a clinical investigation Toll-like receptors and inflammatory bowel disease Innate and adaptive immunity in inflammatory bowel disease Plasmacytoid dendritic cell biology and its role in immune-mediated diseases Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells Aberrant plasmacytoid dendritic cell distribution and function in patients with Crohn's disease and ulcerative colitis University of Texas Medical Branch at Galveston: 1996. Chapter 50 Studies on patients establish Crohn's disease as a manifestation of impaired innate immunity Biologic therapies and risk of infection and malignancy in patients with inflammatory bowel disease: a systematic review and network meta-analysis British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults ACG clinical guideline: preventive care in inflammatory bowel disease Infectious Disease Society of America. IDSA clinical practice guideline for vaccination of the immunocompromised host Receipt of preventive health services by IBD patients is significantly lower than by primary care patients Vaccinating the inflammatory bowel disease patient Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake Inadequate knowledge of immunization guidelines: a missed opportunity for preventing infection in immunocompromised IBD patients Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake Implementing guidelines on the prevention of opportunistic infections in inflammatory bowel disease NUI Galway Researcher Sheds New Light on Vaccine Hesticancy in Ireland and the UK. 2021 Factors influencing COVID-19 vaccination uptake in an elderly sample in Poland Coronavirus vaccine for people with Crohn's or Colitis. Crohn's and Colitis UK Increased incidence of systemic serious viral infections in patients with inflammatory bowel disease associates with active disease and use of thiopurines Estimates of global seasonal influenza-associated respiratory mortality: a modelling study Increased risk of influenza and influenza-related complications among 140,480 patients with inflammatory bowel disease Immunogenicity of highdose trivalent inactivated influenza vaccine: a systematic review and meta-analysis Response to a monovalent 2009 influenza A (H1N1) vaccine Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials MICIVAX Study Group. Immunogenicity and safety of influenza vaccine in inflammatory bowel disease patients treated or not with immunomodulators and/or biologics: a two-year prospective study Serological response to the 2009 H1N1 influenza vaccination in patients with inflammatory bowel disease Immunogenicity of influenza vaccine for patients with inflammatory bowel disease on maintenance infliximab therapy: a randomized trial Immunogenicity of quadrivalent influenza vaccine for patients with inflammatory bowel disease undergoing immunosuppressive therapy Booster influenza vaccination does not improve immune response in adult inflammatory bowel disease patients treated with immunosuppressives: a randomized controlled trial Immunogenicity of high dose influenza vaccine for patients with inflammatory bowel disease on anti-TNF monotherapy: a randomized clinical trial Immunogenicity and safety of high-dose versus standard-dose inactivated influenza vaccine in rheumatoid arthritis patients: a randomised, doubleblind, active-comparator trial Immune response to influenza vaccine in pediatric patients with inflammatory bowel disease Immune response to influenza vaccine in children with inflammatory bowel disease Epidemiological assessment of hepatitis B and C among migrants in the EU/EEA. European Centre for Disease Control and Prevention Non-responders to hepatitis B vaccination: a review Treatment with infliximab or azathioprine negatively impact the efficacy of hepatitis B vaccine in inflammatory bowel disease patients Immune response to hepatitis B vaccination among people with inflammatory bowel diseases: a systematic review and meta-analysis Impact of surveillance of hepatitis b and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: Multicenter prospective observational study (REPENTINA 3) Hepatitis-B vaccine response in inflammatory bowel disease patients: A systematic review and meta-analysis Vaccine Introduced to Primary Schedule Comparison of the effectiveness of two protocols for vaccination (standard and double dosage) against hepatitis B virus in patients with inflammatory bowel disease Fendrix vs engerix-B for primo-vaccination against hepatitis B infection in patients with inflammatory bowel disease: a randomized clinical trial A systematic review of varicella seroprevalence in European countries before universal childhood immunization: deriving incidence from seroprevalence data Clinical trials of varicella vaccine in healthy adolescents and adults Disseminated primary varicella after initiation of infliximab for Crohn's disease Overwhelming varicella pneumonia in a patient with Crohn's disease treated with 6-mercaptopurine Varicella zoster virus infection in inflammatory bowel disease Hospitalization for varicella and zoster in children with inflammatory bowel disease Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation-a systematic review of randomized trials, observational studies and case reports New vaccine technologies to combat outbreak situations Centre for Disease Control The Canarypox-virus vaccine vector ALVAC triggers the release of IFN-gamma by natural killer (NK) cells enhancing Th1 polarization Dysregulation of metabolic pathways in circulating natural killer cells isolated from inflammatory bowel disease patients ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial Oxford-AstraZeneca COVID-19 vaccine efficacy Oxford University/AstraZeneca COVID-19 vaccine approved. Medicines and Healthcare products Regulatory Agency. 2021 EMA recommends COVID-19 Vaccine AstraZeneca for authorisation in the EU. European Medicines Agency. 2021 AstraZeneca vaccine: blood clots are "extremely rare" and benefits outweigh risks, regulators conclude AstraZeneca's COVID-19 Vaccine: EMA Finds Possible Link to Very Rare Cases of Unusual Blood Clots with Low Blood Platelets Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques Interim results of a phase 1-2a trial of Ad26.COV2.S Covid-19 vaccine Announces Single-Shot Janssen COVID-19 Vaccine Candidate Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial. Johnson & Johnson. 2021 EMA recommends COVID-19 Vaccine Janssen for authorisation in the EU. European Medicines Agency (europa.eu). 2021 COVID-19 Vaccine Janssen: EMA finds possible link to very rare cases of unusual blood clots with low platelets. European Medicines Agency (europa.eu). 2021 Second interim analysis of clinical trial data showed a 91.4% efficacy for the Sputnik V vaccine on day 28 after the first dose; vaccine efficacy is over 95% 42 days after the first dose Zika virus protection by a single low-dose nucleoside modified mRNA vaccination Modified mRNA-based vaccines elicit robust immune responses and protect guinea pigs from Ebola virus disease Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaacine-Centre for Disease Control and Prevention Medicines and Healthcare products Regulatory Agency. Confirmation of guidance to vaccination centres on managing allergic reactions following COVID-19 vaccination with the Pfizer/BioNTech vaccine An mRNA vaccine against SARS-CoV-2-preliminary report Moderna announces primary efficacy analysis in phase 3 COVE study for its COVID-19 Vaccine candidate and filing today with U.S FDA for emergency use Authorization COVID-19 vaccine tracker and landscape. WHO. 2021 Neutralizing antibodies against HIV-1 BRU and SF2 isolates generated in mice immunized with recombinant vaccinia virus expressing HIV-1 (BRU) envelope glycoproteins and boosted with homologous gp160 Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondinrelated adhesion protein but not circumsporozoite protein partially protects healthy malarianaive adults against Plasmodium falciparum sporozoite challenge A combined DNA vaccineprime, BCG-boost strategy results in better protection against Mycobacterium bovis challenge Heterologous HA DNA vaccine prime-inactivated influenza vaccine boost is more effective than using DNA or inactivated vaccine alone in eliciting antibody responses against H1 or H3 serotype influenza viruses Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice Heterologous ChAdOxl nCov-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B Effectiveness of COVID-19 vaccine against the B.1.617.2 (Delta) variant restori es/detai l/the-effec ts-of-virus -varia nts-on-covid -19-vacci nes?gclid = C j w KC A j w-e 2 E B h A h E i w A J I 5 j g x-m G H z6 B e t 8 5 sR gnS XQ Q uB Serological response to COVID-19 vaccination in IBD patients receiving biologics Contributors to the CLARITY IBD Study. Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting 7th Interview COVID-19 ECCO Taskforce Providing guidance during a global viral pandemic for the care of patients with inflammatory bowel disease