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1.
Clin Exp Immunol ; 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1621554

ABSTRACT

B cell depleting agents are amongst the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B cell depleting agents: a cohort of patients treated for haematological B cell malignancy and another treated for rheumatological disease. B cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B cell reconstitution, however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses, however shorter intervals between vaccine doses (<1m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B cell depleting agents (>36m previously) vaccine non-responsiveness was independent of peripheral B cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2.

3.
BMJ Open ; 11(6): e048856, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1270894

ABSTRACT

OBJECTIVE: A key challenge towards a successful COVID-19 vaccine uptake is vaccine hesitancy. We examine and provide novel insights on the key drivers and barriers towards COVID-19 vaccine uptake. DESIGN: This study involved an anonymous cross-sectional online survey circulated across the UK in September 2020. The survey was designed to include several sections to collect demographic data and responses on (1) extent of agreement regarding various statements about COVID-19 and vaccinations, (2) previous vaccination habits (eg, if they had previously declined vaccination) and (3) interest in participation in vaccine trials. Multinominal logistic models examined demographic factors that may impact vaccine uptake. We used principle component analysis and text mining to explore perception related to vaccine uptake. SETTING: The survey was circulated through various media, including posts on social media networks (Facebook, Twitter, LinkedIn and Instagram), national radio, news articles, Clinical Research Network website and newsletter, and through 150 West Midlands general practices via a text messaging service. PARTICIPANTS: There were a total of 4884 respondents of which 9.44% were black, Asian and minority ethnic (BAME) group. The majority were women (n=3416, 69.9%) and of white ethnicity (n=4127, 84.5%). RESULTS: Regarding respondents, overall, 3873 (79.3%) were interested in taking approved COVID-19 vaccines, while 677 (13.9%) were unsure, and 334 (6.8%) would not take a vaccine. Participants aged over 70 years old (OR=4.63) and the BAME community (OR=5.48) were more likely to take an approved vaccine. Smokers (OR=0.45) and respondents with no known illness (OR=0.70) were less likely to accept approved vaccines. The study identified 16 key reasons for not accepting approved vaccines, the most common (60%) being the possibility of the COVID-19 vaccine having side effects. CONCLUSIONS: This study provides an insight into focusing on specific populations to reduce vaccine hesitancy. This proves crucial in managing the COVID-19 pandemic.


Subject(s)
COVID-19 , Vaccines , Aged , COVID-19 Vaccines , Cross-Sectional Studies , Female , Humans , Male , Pandemics , SARS-CoV-2 , United Kingdom , Vaccination
4.
Trials ; 22(1): 296, 2021 Apr 20.
Article in English | MEDLINE | ID: covidwho-1195925

ABSTRACT

BACKGROUND: Developing a safe and effective vaccine will be the principal way of controlling the COVID-19 pandemic. However, current COVID-19 vaccination trials are not adequately representing a diverse participant population in terms of age, ethnicity and comorbidities. Achieving the representative recruitment targets that are adequately powered to the study remains one of the greatest challenges in clinical trial management. To ensure accuracy and generalisability of the safety and efficacy conclusions generated by clinical trials, it is crucial to recruit patient cohorts as representative as possible of the future target population. Missing these targets can lead to reduced validity of the study results and can often slow down drug development leading to costly delays. OBJECTIVE: This study explores the key factors related to perceptions and participation in vaccination trials. METHODS: This study involved an anonymous cross-sectional online survey circulated across the UK. Statistical analysis was done in six phases. Multi-nominal logistic models examined demographic and geographic factors that may impact vaccine uptake. RESULTS: The survey had 4884 participants of which 9.44% were Black Asian Minority Ethnic (BAME). Overall, 2020 (41.4%) respondents were interested in participating in vaccine trials; 27.6% of the respondents were not interested and 31.1% were unsure. The most interested groups were male (OR = 1.29), graduates (OR = 1.28), the 40-49 and 50-59 age groups (OR = 1.88 and OR = 1.46 respectively) and those with no health issues (OR = 1.06). The least interested groups were BAME (OR = 0.43), those from villages and small towns (OR = 0.66 and 0.54 respectively) and those aged 70 and above (OR = 1.11). CONCLUSIONS: In order to have a vaccination that is generalisable to the entire population, greater work needs to be done in engaging a diverse cohort of participants. Public health campaigns need to be targeted in improving trial recruitment rates for the elderly, BAME community and the less educated rural population.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Clinical Trials as Topic , Patient Selection , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pandemics , Surveys and Questionnaires , United Kingdom , Vaccination , Young Adult
6.
Eur J Haematol ; 105(5): 540-546, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-742085

ABSTRACT

Emerging data from the management of patients with coronavirus disease 2019 (COVID-19) suggests multi-systemic involvement, including the hemopoietic system. The haematological manifestations of COVID-19 include blood count anomalies notably lymphopenia and neutrophilia which are of prognostic significance. Hyperferritinemia and elevated lactate dehydrogenase have also been associated with increased mortality. Furthermore, there is considerable evidence of a distinct coagulopathy associated with COVID-19 characterised by elevated D-dimers and an increased risk of thrombotic events. This comprehensive review summarises the latest evidence from published studies and discusses the implications of the various haematological manifestations of COVID-19 with a view to guiding clinical management and risk stratification in this rapidly evolving pandemic.


Subject(s)
Blood Coagulation Disorders/etiology , COVID-19/blood , COVID-19/complications , Lymphopenia/etiology , Anticoagulants/therapeutic use , Biomarkers/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/drug therapy , COVID-19/drug therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Inflammation Mediators/blood , Leukocyte Disorders/blood , Leukocyte Disorders/etiology , Lymphocyte Count , Lymphopenia/blood , Neutrophils , Pandemics , Risk Factors , SARS-CoV-2 , Thrombosis/blood , Thrombosis/etiology
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