Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities.

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4+ and CD8+ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.

Robust SARS-CoV-2 T cell responses with common TCRαß motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells.

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%-75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.

The Effects of the COVID Pandemic on Patients with IBD: Lessons Learned and Future Directions.

The COVID-19 pandemic has caused extended global disruption and changed healthcare behaviour and delivery in patients with inflammatory bowel disease, many of whom take immune modifying treatment. Although there were fears about the vulnerability of IBD patients to SARS-CoV-2 infection, we have learnt that overall IBD patients are equivalent to the general population in both viral acquisition and infection outcomes. Overall IBD patients obtain effective vaccine-induced immune responses, although in some groups an additional vaccine dose is required to constitute a primary course. The pandemic has led to significant changes in healthcare delivery, some of which will be enduring. As we grapple with the challenges of recovery, the lessons learnt will continue to be important in optimising outcomes in future outbreaks.

Misconceptions Drive COVID-19 Vaccine Hesistancy in Individuals with Inflammatory Bowel Disease

Background Vaccination is an effective public health measure to combat the SARS-CoV-2 pandemic. However, vaccine “hesitancy” has limited uptake in some, including inflammatory bowel disease (IBD) patients who may have unique concerns influencing uptake. Aim The aim of the study is to explore attitudes, concerns, and the influence of different sources of information on COVID-19 vaccine uptake in IBD patients. Methods Patients from a specialist IBD clinic at a tertiary hospital in Australia and a national IBD patient society were invited to complete an anonymous online survey regarding COVID-19 vaccination. Demographic characteristics, attitudes towards vaccination, and trust in sources of information were explored. Logistic regression was used to identify variables associated with vaccine uptake. Results Of 441 respondents, 93% of respondents had received at least 1 dose of COVID-19 vaccination. Self-perceived risk of being more unwell with COVID-19 infection due to IBD (AOR 5.25, 95% CI 1.96–14.04, p < 0.001) was positively associated with vaccine uptake. Concerns regarding the safety of vaccination in pregnancy (OR 0.22, 95% CI 0.08–0.65, p=0.006) and of causing an IBD flare (OR 0.28, 95% CI 0.10–0.77, p=0.01) were negatively associated with vaccine uptake. In total, 282 (73.7%) responders ranked healthcare workers the most trusted source to obtain information surrounding vaccination. Conclusion Vaccine hesitancy in IBD patients is low. Concerns about the safety of vaccination in pregnancy and in causing an IBD flare are both associated with vaccine hesitancy. Healthcare providers play a key role in proactively addressing these misconceptions particularly in the context of emerging virus variants and the availability of boosters.

SARS-CoV-2 vaccination in patients with inflammatory bowel disease.

BACKGROUND: The current COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has drastically impacted societies worldwide. Vaccination against SARS-CoV-2 is expected to play a key role in the management of this pandemic. Inflammatory conditions such as inflammatory bowel disease (IBD) often require chronic immunosuppression, which can influence vaccination decisions. AIM: This review article aims to describe the most commonly available SARS-CoV-2 vaccination vectors globally, assess the potential benefits and concerns of vaccination in the setting of immunosuppression and provide medical practitioners with guidance regarding SARS-CoV-2 vaccination in patients with IBD. METHODS: All published Phase 1/2 and/or Phase 3 and 4 studies of SARS-CoV-2 vaccinations were reviewed. IBD international society position papers, safety registry data and media releases from pharmaceutical companies as well as administrative and medicines regulatory bodies were included. General vaccine evidence and recommendations in immunosuppressed patients were reviewed for context. Society position papers regarding special populations, including immunosuppressed, pregnant and breast-feeding individuals were also evaluated. Literature was critically analysed and summarised. RESULTS: Vaccination against SARS-CoV-2 is supported in all adult, non-pregnant individuals with IBD without contraindication. There is the potential that vaccine efficacy may be reduced in those who are immunosuppressed; however, medical therapies should not be withheld in order to undertake vaccination. SARS-CoV-2 vaccines are safe, but data specific to immunosuppressed patients remain limited. CONCLUSIONS: SARS-CoV-2 vaccination is essential from both an individual patient and community perspective and should be encouraged in patients with IBD. Recommendations must be continually updated as real-world and trial-based evidence emerges.

Managing COVID-19 in patients with inflammatory bowel disease: navigating unprecedented challenges.

The COVID-19 pandemic has demanded a rapid adaptation in healthcare provision, including patients with inflammatory bowel disease (IBD). This viewpoint discusses some of the unique challenges in managing comorbid IBD and COVID-10 experienced by our team at The Royal Melbourne Hospital, which was at the epicentre of the COVID-19 'second-wave' surge in Melbourne.

Guidance for Restarting Inflammatory Bowel Disease Therapy in Patients Who Withheld Immunosuppressant Medications During COVID-19.

Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.

Practical management of inflammatory bowel disease patients during the COVID-19 pandemic: expert commentary from the Gastroenterological Society of Australia Inflammatory Bowel Disease faculty.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has emerged as a public health emergency and challenged healthcare systems globally. In a minority of patients, SARS-CoV-2 manifests with a severe acute respiratory illness and currently there is insufficient data regarding the virulence of COVID-19 in inflammatory bowel disease patients taking immunosuppressive therapy. This review aims to summarise the current literature and provide guidance on the management of inflammatory bowel disease patients in the context of the COVID-19 pandemic in the Australasian setting.