Opioid Policy Changes During the COVID-19 Pandemic - and Beyond

The United States is currently in the midst of 2 public health emergencies: COVID-19 and the ongoing opioid crisis. In an attempt to reduce preventable harm to individuals with opioid use disorder (OUD), federal, state, and local governments have temporarily modified law and policy to increase access to OUD treatment and divert some individuals at high risk away from the correctional system. In this Commentary, we briefly describe how people with OUD are at increased risk for COVID-19, discuss existing policy barriers to evidence-based prevention and treatment for individuals with OUD, explain the temporary rollbacks of those barriers, and argue that these changes should be made permanent. We also suggest several additional steps that federal and state governments can urgently take to reduce barriers to care for individuals with OUD, both during the current crisis and beyond. Copyright © 2020 American Society of Addiction Medicine.

A case of anaphylaxis to the BNT162b2 mRNA COVID-19 vaccine in a patient with confirmed polyethylene glycol allergy

Case report The Food and Drug Administration (FDA) provided emergency use authorization (EUA) for the Pfizer/BioNTech (BNT162b2) COVID-19 vaccine in December 2020. Implementation of COVID-19 mass vaccination efforts were implemented soon after. However, following the FDAs EUA, COVID-19 vaccine allergic reactions were reported. These findings led to concerns about vaccine hesitancy and the possible avoidance of future doses. The Texas Children's Hospital COVID-19 Vaccine Hypersensitivity Clinic was established in December 2020 to help address these concerns and to evaluate both pediatric and adult patients with immediate allergic reactions to the COVID-19 vaccines, as well as evaluating patients with polyethylene glycol (PEG) or polysorbate (PS) allergy. We present the case of an 18yo female who experienced anaphylaxis following her second Pfizer mRNA COVID-19 vaccine. The patient developed symptoms of generalized hives, chest tightness and dyspnea 17 minutes after receiving the Pfizer mRNA COVID-19 vaccine. She was treated in the emergency department with IM prednisone and PO diphenhydramine. Of note, in 2018, she had a similar response to her HPV9 vaccine (containing PS 80). Tryptase wasn't obtained at the time of her COVID-19 or HPV9 vaccine reactions, but she did have a baseline that was normal around 4ng/mL. Skin testing was performed to the following: PEG 3350, PS 20 and PS 80. Skin testing (skin prick and intradermal) were negative for PS20 and PS80. PEG 3350 skin prick was negative but methylprednisone acetate (PEG 3350) was positive at the 4mg/mL intradermal testing strength. She underwent a Miralax (PEG 3350) oral challenge. Within 20 minutes of ingesting 0.17grams PEG 3350 she developed an itchy macular rash on neck and upper chest, nausea and a globus throat sensation. She was treated with PO cetirizine and symptoms improved. Tryptase level was obtained 30 min after the start of her reaction and was 4ng/mL. Given the patient's reaction, she was advised to avoid PEG containing products and will return to undergo a graded-step challenge to the Janssen (J&J) COVID-19 vaccine. The prevalence of COVID-19 mRNA vaccine anaphylaxis and PEG allergies is rare. However, allergy referral is warranted in cases of immediate reactions to the COVID-19 vaccine or history of PEG or polysorbate allergies.

Multidisciplinary Virtual Tumor Boards (VTB): A Single Center Satisfaction Survey

INTRODUCTION: With the onset of the COVID-19 pandemic, many cancer centers pivoted to a completely virtual multidisciplinary tumor board (VTB) format. We previously published a significant rise in number of attendees and cases presented with the transition from in-person to VTB at our institution. The aim of the current study was to measure the satisfaction of participants regarding the virtual format. METHOD(S): We developed a 21-question survey including 10 questions that directly compared virtual to in-person tumor boards using a 5-point Likert scale. The survey was imported into REDCap and sent via email to all tumor board participants. Responses were collected for approximately 4 weeks (reminder email at 2 weeks) and categorized. RESULT(S): There were a total of 83 respondents, 53 of whom (64%) attended both in-person and VTB. Specialties with highest response rates were Surgical Oncology (n=24) and Medical Oncology (n=18), and tumor boards with highest participation in the survey were Breast (n=26) and Gastrointestinal (n=21). Most respondents accessed the virtual platform from the hospital or office (67%) with some participation from home (19%). Most (77%) participants were either satisfied or very satisfied with the VTB format compared with 70% for in-person tumor board. Additionally, the majority of respondents (95%) felt that VTBs had great value for discussions with community-based clinicians. In terms of direct comparison to in-person tumor boards, 40% felt that the level of distraction was higher for VTB. The large majority of respondents felt that they were somewhat more (24%) or significantly more (44%) available for VTB format. Finally, when asked regarding their preference going forward, 52% favored virtual, 6% favored in-person, and 42% favored some sort of hybrid variety type of tumor board. CONCLUSION(S): The majority of multidisciplinary tumor board participants expressed satisfaction with the virtual format and prefer it to in-person meetings going forward. VTB allows increased accessibility, opportunities to engage community oncologists, and the ability to present more cases. Drawbacks to this format included less face-to-face interaction and increased levels of distraction. Our institution is currently considering completely virtual and hybrid options moving forward.

Shared Mobility Opportunities and Their Computational Challenges for Improving Health-Related Quality of Life

Shared mobility has emerged in urban spaces as an alternative to owning and maintaining a vehicle, by allowing flexible and short-term mobility services at low costs. These mobility options act as promising sources of trips benefiting people in vulnerable groups and enabling them to access essential services such as healthcare and providing transport during emergency evacuations. Shared mobility services can also make the cities more sustainable and healthy for all inhabitants by reducing the number of circulating vehicles. Fewer vehicles in the urban traffic makes the air cleaner and the environment less noisy, reducing risks of respiratory, and cardiovascular diseases and improving the people's health-related quality of life. However, managing shared mobility services intensifies transport challenges. Amid these challenges are reducing operational costs and diminishing health hazards such as the ones posed by COVID-19. © 2021 Elsevier Ltd. All rights reserved

Using simulation to prepare social work students for field education

This research explores the use of simulation technology in supporting and preparing social work students (n = 336) for core professional skills needed for practice. This study utilized a randomized experimental design using a 3 × 3 between-subjects design to assess the impact of the type of simulation (e.g. traditional written case studies, video-based simulations, and live actor simulations) and type of scenario (e.g. family/domestic violence, suicide/mental health and hospital/medical) on social work student's ability to undertake a psychosocial assessment. Results showed that students developed more comprehensive psychosocial assessments when presented with video simulations compared to traditional methods, using actors or written case studies. This research builds evidence for social work to embrace the use of simulation to develop these skills for students in a practice setting that removes not only the fear of doing harm but also the real possibility of harm in complex scenarios. Social work field education is under increasing pressure to meet professional standards, especially with the impact of the COVID pandemic. Thus, the profession must consider alternatives for training students including utilizing technology. While many other professional disciplines incorporated the use of simulation in training, social work has been slow to embrace this trend while favoring traditional teaching methods. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages.

The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e. USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titres did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.

SARS-CoV-2: A Rapid Review On The Effectiveness Of Face Coverings To Reduce Transmission

Introduction. At various stages of the COVID-19 pandemic, face coverings have been recommended and encouraged as one of the interventions to reduce transmission of the SARS-CoV-2 virus. However, in the earlier stages of the pandemic, decisions on face coverings relied primarily on evidence based on other viral respiratory infections. More direct evidence on the use of face coverings with COVID-19 developed in tandem with the pandemic. Health Technology Wales undertook an ultra-rapid review to inform national guidelines, the work assessed the evidence on the effectiveness of face coverings to reduce SARS-CoV-2 transmission. We also reviewed evidence on the efficacy of different types of face coverings. Methods.Weconducted a systematic literature search for evidence to address (i) the effectiveness of face coverings to reduce the spread of COVID-19 in the community, and (ii) the efficacy of different types of face coverings designed for use in community settings. We identified a rapid review in 2021 by Public Health England that closely aligned with our review questions. This provided the main source for identifying relevant studies, supplemented by a search for publications following their search date. Results. We identified two evidence reviews (including the Public Health England review) that examined the effectiveness of face coverings on reducing transmission of SARS-CoV-2;reporting on 31 and 39 studies, respectively. Two further primary studies were published after the two evidence review searches were included. Overall, the evidence suggested that face coverings may provide benefits in preventing SARS-CoV-2 transmission, although the higher-quality studies suggested that these benefits may be modest. Medical masks appeared to have higher efficacy than fabric masks, although the evidence was mixed. Conclusions. At the time of this review, evidence on the effectiveness of face coverings remains limited and conclusions rely on low-quality sources of evidence with high risk of bias, although higher-quality evidence points to some benefit. Face coverings may play a role in preventing transmission of SARS-CoV-2, particularly as part of a bundle of other preventative measures.

Helping the Helpers: Adaptation and Evaluation of Stress First Aid for Healthcare Workers in the Veterans Health Administration During the COVID-19 Pandemic.

BACKGROUND: Early interventions are needed to support the behavioral health of healthcare staff in the context of the COVID-19 pandemic. Stress First Aid (SFA) is a self-care and peer support model for reducing burnout and stress that is designed for use in high-stress occupations. METHODS: We conducted a mixed-methods evaluation of an SFA program in the Veterans Health Administration (VHA). This brief, multi-session, didactic program was adapted for hospital workgroups. Program attendees completed a survey assessing implementation outcomes, burnout, stress, mood, and SFA skills at the beginning (N = 246) and end (n = 94) of the SFA program and a subgroup (n = 11) completed qualitative feedback interviews. FINDINGS: Program acceptability, appropriateness, and feasibility were rated highly. From pre- to post-SFA, the impact of the pandemic on stress and anxiety, as well as proficiency in supporting peers increased. Qualitative findings suggest the program provided a shared language to discuss stress, normalized stress reactions, met a need for stress management tools, and helped staff feel valued, empowered, connected with each other. Staff reported being more aware of their stress, but SFA was insufficient to address many of the systemic sources of burnout and stress. CONCLUSIONS AND APPLICATIONS TO PRACTICE: While the SFA program was well received, the impact of brief programs is likely to be modest when implemented in the middle of an ongoing pandemic and when burnout arises from chiefly from systemic sources. Lessons learned during the program implementation that may guide future efforts are discussed.

Digital Blackface and the Troubling Intimacies of TikTok Dance Challenges

During the coronavirus pandemic, TikTok dance challenges offered an escape for isolated young Americans of all backgrounds to play and connect. For Black femme creators like Keara Wilson, who choreographed one of first viral challenges of the pandemic, however, the uneven rewards for white influencers performing Black dances within TikTok’s digital attention economy implicitly signals what Jason Parham refers to as an “evolution of digital blackface.” On TikTok, digital blackface is characterized by predatory inclusion, cultural extraction, and fungibility. Encompassing these features, dance challenges offer a complex site to examine the racial and gender violence of platform capitalism within today’s most ascendant social media platform. Placing Wilson’s #SavageChallenge within the historical context of blackface minstrelsy and chattel slavery, this chapter argues that the uneven rewards for white performers of Black dances on TikTok constitutes a discreet yet insidious form of digital blackface that troubles the contours of Gen Z’s supposed racial progressivism. This chapter offers a scale for evaluating cross-racial intimacies of dance challenge participation, from playful exchange to cultural extraction. The chapter concludes by considering how platforms and influencers might undermine this exploitative digital economy through legal intervention and justice-oriented investments. © 2022 selection and editorial matter, Trevor Boffone;individual chapters, the contributors. All rights reserved.

Meeting the needs of rural/regional cancer patients in survivorship: Understanding age differences in the role of telehealth

4The University of the sunshine Coast, Sippy Downs, QLD, Australia Background and Aims: Access to health services and quality of life are important factors for long-term cancer survivorship. The COVID-19 pandemic has significantly impacted cancer care globally. In response to the pandemic, reconfiguration of services and adoption of telehealth have been essential for continuation of services, while also offering an alternative approach to cancer care and support. This study explores the role of telehealth in providing health and supportive services to Australian rural/regional cancer patients during COVID-19 and their attitudes on the quality of these services to inform future practice. Method(s): Rural/regional cancer patients and survivors (n = 66) completed an online survey regarding the transition and delivery of health and support services via telehealth during COVID-19. Data was collected as part of a bi-annual survey on client satisfaction at a rural/regional community cancer wellness centre in Australia. Result(s): Participants included 71% females with 48% younger (under 64 years), and 52% older cancer patients and survivors (65 years and over), with a mix of cancer presentations. Younger participants were significantly (p < 0.05) more likely to use allied health services via video/telehealth during COVID-19 compared to their older counterparts. The preferred format for nursing health services in the future was face-to-face (59% for younger and42%for older participants) telehealth (10% for both groups), and mixed (31% for younger and 48% for older participants). Although not statistically significant (p>.05), it is interesting that the older cohort had a greater preference for a mixed modality of face-to-face and telehealth in meeting their future health service needs. Conclusion(s): Telehealth has benefits for the delivery of health and supportive services to rural/regional cancer patients. Nurses can play a key role in assessing the support needs of cancer survivors and facilitate strategies to ensure that survivors have the skills necessary to access telehealth support.

An"Early Adopter" of CPQR's Patient Reported Outcome (PRO) Initiative: Lessons Learned Through Implementation of an Electronic PRO Platform Across a Mulit-Center Radiation Oncology Department

Purpose: Beyond patient symptom management during treatment, patient reported outcomes (PRO) play a critical role in oncology survivorship. Although considered standard of care, PRO collection and use is challenging for radiotherapy (RT) centres lacking electronic PRO (ePRO) infrastructure. This work outlines facilitators and barriers to the implementation of an ePRO program across a multicentre radiation oncology department. Material(s) and Method(s): Dalhousie University's Department of Radiation Oncology (DRO) is composed of four RT centres across three provinces. Department-wide implementation of ePRO was precipitated by several key events: In 2009, a Canadian Partnership Against Cancer (CPAC) grant enabled 2 centres to begin paper-based PRO using the Canadian Problem Checklist (CPC) and Edmonton Symptom Assessment System (ESASr). In 2015, the Department's research retreat set ePRO as a priority. In 2017, Accreditation Canada mandated routine evaluation of patient outcomes and in 2018, the Canadian Partnership for Quality Radiotherapy (CPQR) identified Dalhousie's DRO as an early adopter within the pan-Canadian PRO initiative. In 2019, three DRO centres were awarded CPAC funding to launch ePROs. The fourth centre now hopes to use lessons learned in order to facilitate their ePRO implementation. Result(s): ePRO was launched in September 2021 with a phased approach across centres and tumour sites so that user feedback can inform the roll out. Clinic workflows now includes ePRO at consultation, first and last RT review as well as follow-up. Within the ePRO application (Noona), CPQR-endorsed PRO tools include CPC, ESASr, and the Brief Pain Inventory (BPI), with use of other tumour-site specific questionnaires planned. Project charter included needs assessments (human resource, staff /patient education) and change management strategies required to obtain buy-in from front line staff. Although coordination of such a large-scale initiative was challenged by COVID restrictions, project priority was escalated with ePRO recognized as a powerful tool to assess patient symptoms in clinic or remotely. Research unit support was invaluable to navigate IT project complexities including vendor/collaborator contracts, processes of Privacy Impact Assessments and IT architectural reviews. From the advisory board to PRO working groups, mullti-stakeholder feedback and collaboration has been key, including representatives of patients, cancer program leadership, project managers/principle investigators, administrative staff, nurses, radiation therapists, radiation oncologists, industry, IT and legal. Conclusion(s): Multi-centre implementation of an ePRO program has been feasible but complex and time intensive. It is hoped that our lessons learned may benefit those RT centres aiming to transition from paper-based to ePRO systems. With critical electronic infrastructure now in place, we await data to analyze ePRO amongst other patient outcomes in ongoing RT Big Data initiatives. Copyright © 2022 Elsevier Ireland Ltd. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Influenza A(H7N9) Pandemic Preparedness: Assessment of the Breadth of Heterologous Antibody Responses to Emerging Viruses from Multiple Pre-Pandemic Vaccines and Population Immunity.

Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 µg hemagglutinin (HA)/dose + AS03A; 2. inactivated vaccine with 5.75 µg HA/dose + AS03A; 3. inactivated vaccine with 11.5 µg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 µg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9).

Good Law to Fight Bad Bugs: Legal Responses to Epidemics

Although epidemics are generally understood as lying within the domain of biomedicine, legal and social arrangements play crucial roles in determining whether or not infectious disease outbreaks grow into epidemics and even pandemics. Yet epidemics are challenging terrain for legal regulation. Because epidemics cross political borders and span jurisdictional boundaries, funding for epidemic prevention, preparedness, and response is always inadequate and coordination is difficult. Because epidemics require rapid and nimble responses, governments and international organizations often declare states of emergency, thereby evading some of the usual strictures of law. And because they involve massive uncertainty and rapidly evolving health crises, they require legal actors to work more quickly and with lower standards of proof than is common in law and to intrude on the turf of medical and scientific professionals. Legal contributions to pandemic management could be improved if legal measures such as global treaties and domestic public health law took account of these special features of epidemics.

Centering Adult ESOL Students in the Museum Through Art and Art-Making

In 2020, the Brooklyn Museum Education Department, like many departments in museums across the globe, engaged in a reevaluation of its programs and priorities in light of the COVID-19 pandemic. As we reassessed what responsive programming could and should look like for our audiences, the Adult Learning Division within Education decided to prioritize further developing our adult literacy initiatives, including programs and partnerships for English for Speakers of Other Languages (ESOL) students and teachers. One such partnership resulted in a template for incorporating art-making in language learning and for centering the voices of adult language learners within the context of a public pop-up talk at the Museum. This article shares some of the lessons the museum educator, ESOL teacher, and ESOL students learned through the collaboration, as well as reflections from the public at the culminating event as revealed through survey work.

Giant Cell Arteritis: A Case-Based Narrative Review of the Literature.

PURPOSE OF REVIEW: Giant cell arteritis (GCA) is a chronic, inflammatory condition, primarily affecting the medium and larger arteries. The purpose of this narrative review is to describe GCA in the context of headache and facial pain, based on a case and the available current literature. Understanding the etiology, pathophysiology, the associated conditions, and the differential diagnoses is important in managing GCA. RECENT FINDINGS: In a patient presenting with unilateral facial/head pain with disturbances of vision, GCA should be considered in the differential diagnosis. There is an association of GCA with several comorbid conditions, and infections including coronavirus-19 (COVID-19) infection. Management of GCA primarily depends upon the identification of the affected artery and prompt treatment. Permanent visual loss and other serious complications are associated with GCA. GCA is characterized by robust inflammation of large- and medium-sized arteries and marked elevation of systemic mediators of inflammation. An interdisciplinary approach of management involving the pertinent specialties is strongly recommended.

Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.

CLL-VR: A UK study of vaccine responses in patients with B-cell chronic lymphocytic leukaemia

B-cell chronic lymphocytic leukaemia (CLL) is associated with immune suppression and patients are at increased risk following SARS-CoV-2 infection. The Chronic Lymphocytic Leukaemia-Vaccine Response (CLL-VR) study was designed to assess immune responses following the introduction of Covid-19 vaccination in UK. Five hundred patients with CLL were recruited nationally through NHS and charity communications. Phlebotomy blood samples were taken from local patients ( n = 100) and dried blood spot samples were collected via post from participants across the UK ( n = 400). Ninety-six age-matched control subjects were also recruited locally. Samples were taken at 2-3 weeks following the first, second and third primary vaccine doses. Antibody and cellular responses against spike protein, and neutralising antibody titre to delta and omicron variant, were measured. Total serum immunoglobulin level was also determined. Responses were analysed according to clinical history, serum immunoglobulin level and vaccine type received. Donors with a clinical or serological history of prior natural infection were excluded from the analysis. Twenty percent (70/353) of participants developed a measurable antibody response after the first vaccination and this increased to 67% (323/486) following the second dose and 80% (202/254) after a third dose. The response rate in healthy controls plateaued at 100% after only two doses. The magnitude of the antibody response was also 3.7-fold lower following the second vaccine compared to controls ( n = 244;490 vs. 1821 U/ml, p < 0.0001) but increased markedly to 3114 U/ ml after third dose ( n = 51). No difference was observed in relation to the initial vaccine platform received. Multivariate analysis on 486 participants showed that BTKi therapy, history of recurrent infection and low serum antibody levels of IgA or IgM were independent prognostic markers for poor antibody response. Among participants with a detectable antibody response, a marked reduction in the ability to neutralise the delta and omicron variants of concern was noted compared to healthy controls following both the second and third dose of vaccine. Cellular responses were assessed following the second vaccine by IFN-g ELISPOT ( n = 91). Patients who had received the ChAdOx1 vaccine had similar levels to controls ( p = 0.39), while those who had received BNT162b2 had lower levels ( p < 0.0001). Five patients with poor spike-specific antibody responses to vaccination subsequently developed breakthrough infection with SARS-CoV-2 delta variant. Antibody responses and neutralisation remained poor following recovery from infection although T-cell responses were strong and only one patient required hospital admission. CLL-VR is the largest vaccine study conducted in patients with CLL and reveals diminished but comparable antibody responses to both the ChAdOx1 and BNT162b2 vaccines with some improvement following third primary dose of mRNA vaccine. In contrast T-cell responses following second dose are greater in those who received ChAdOx1 platform. Low neutralising activity against the delta and omicron variants highlights an ongoing risk for this vulnerable population despite repeated vaccination and reveals the need for alternative approaches to protection including prophylactic monoclonal antibody therapy..