It is generally recommended that medications only be used in pregnancy where the potential harms to both the mother and foetus are outweighed by the potential benefits. Despite the known harms associated with alcohol consumption during pregnancy, the use of medication for the treatment of pregnant women with an alcohol use disorder (AUD) appears to be rare. This is likely due to the lack of available data regarding the safety of these medications in pregnancy. We reviewed the literature and weighed up the harms associated with alcohol use and AUD during pregnancy with the potential benefits of medications for AUD in pregnancy, including acamprosate, naltrexone and disulfiram. There is little published evidence to support the safety of medications for AUD in pregnancy. However, from the research available it is likely that only disulfiram has the potential to cause serious foetal harm. While further research is required, acamprosate and naltrexone do not appear to be associated with substantial risks of congenital malformations or other serious consequences. Given the potential risks associated with alcohol consumption during pregnancy, the use of acamprosate and naltrexone should be considered for the treatment of pregnant women with AUD based on the current evidence base, although more research is warranted.
\n \n\n \n \nBackground: Electronic health care data contain rich information on medicine use from which adherence can be estimated. Various measures developed with medication claims data called for transparency of the equations used, predominantly because they may overestimate adherence, and even more when used with multiple medications. We aimed to operationalize a novel calculation of adherence with polypharmacy, the daily polypharmacy possession ratio (DPPR), and validate it against the common measure of adherence, the medication possession ratio (MPR) and a modified version (MPRm). Methods: We used linked health data from the Australian Pharmaceutical Benefits Scheme and Western Australian hospital morbidity dataset and mortality register. We identified a strict study cohort from 16,185 patients aged \u226565 years hospitalized for myocardial infarction in 2003\u20132008 in Western Australia as an illustrative example. We applied iterative exclusion criteria to standardize the dispensing histories according to previous literature. A SAS program was developed to calculate the adherence measures accounting for various drug parameters. Results: The study cohort was 348 incident patients (mean age 74.6\u00b16.8 years; 69% male) with an admission for myocardial infarction who had cardiovascular medications over a median of 727 days (range 74 to 3,798 days) prior to readmission. There were statins (96.8%), angiotensin converting enzyme inhibitors (88.8%), beta-blockers (85.6%), and angiotensin receptor blockers (13.2%) dispensed. As expected, observed adherence values were higher with mean MPR (median 89.2%; Q1: 73.3%; Q3: 104.6%) than mean MPRm (median 82.8%; Q1: 68.5%; Q3: 95.9%). DPPR values were the most narrow (median 83.8%; Q1: 70.9%; Q3: 96.4%). Mean MPR and DPPR yielded very close possession values for 37.9% of the patients. Values were similar in patients with longer observation windows. When the traditional threshold of 80% was applied to mean MPR and DPPR values to signify the threshold for good adherence, 11.6% of patients were classified as good adherers with the mean MPR relative to the DPPR. Conclusion: In the absence of transparent and standardized equations to calculate adherence to polypharmacy from refill databases, the novel DPPR algorithm represents a valid and robust method to estimate medication possession for multi-medication regimens.
\n \n\n \n \nTreatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19.
\n \n\n \n \nBACKGROUND: There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins. METHODS: In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351). FINDINGS: We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), an increase in binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) is observed following each additional dose. In addition, a strong and polyfunctional T cell response was measured all booster regimens. INTERPRETATION: Real world data is demonstrating that one or more doses of licensed SARS-CoV-2 vaccines confer reduced protection against hospitalisation and deaths caused by divergent VoC, including Omicron. Our data support the ongoing clinical development and testing of booster vaccines to increase immunity against highly mutated VoC. FUNDING: This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.
\n \n\n \n \nThe trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.
\n \n\n \n \nThe speed of COVID-19 vaccine development has been identified as a central concern contributing to hesitancy in acceptance. We conducted qualitative interviews to gain a greater understanding into these concerns and to identify what might address them. Twelve qualitative interviews were conducted with participants identifying as hesitant for COVID-19 vaccination and reporting concern about the speed of vaccine development. Interpretative Phenomenological Analysis (IPA) was used. Concerns about speed comprised the linked themes of i) difficulty understanding the pace, and, ii) worry about the implications for vaccine safety. Uncertainties concerning the pandemic led to a notable desire for credible and understandable information regarding the vaccines, which many participants felt was not available. Four routes to resolving uncertainty about whether to be vaccinated were identified. First, waiting for more information about the vaccines, such as about their contents and impact on transmission. Second, a growing perception that the vaccines must be safe given the large numbers already vaccinated. Third, viewing the vaccines as necessary - even if unappealing - for ending the pandemic. Finally, a feeling that there would be no choice but to have a vaccine. Examples of what might reduce hesitancy were given, including interviews with vaccine developers and knowing others of similar age having safely been vaccinated. The pace of development broke expectations set earlier in the pandemic. This was interpreted negatively due to a perceived lack of credible information. Most participants could envisage ways their concerns could be resolved, enough for them to have a vaccine.
\n \n\n \n \nBACKGROUND: The longitudinal antigen-specific immunity in COVID-19 convalescents is crucial for long-term protection upon individual re-exposure to SARS-CoV-2, and even more pivotal for ultimately achieving population-level immunity. To better understand the features of immune memory in individuals with different disease severities at one year post-disease onset we conducted this cohort study. METHODS: We conducted a systematic antigen-specific immune evaluation in 101 COVID-19 convalescents, who had asymptomatic, mild, moderate, or severe disease, through two visits at months 6 and 12 post-disease onset. The SARS-CoV-2-specific antibodies, comprising NAb, IgG, and IgM, were assessed by mutually corroborated assays, i.e. neutralization, enzyme-linked immunosorbent assay (ELISA), and microparticle chemiluminescence immunoassay (MCLIA). Meanwhile, the T-cell memory against SARS-CoV-2 spike, membrane and nucleocapsid proteins was tested through enzyme-linked immunospot assay (ELISpot), intracellular cytokine staining (ICS), and tetramer staining-based flow cytometry, respectively. RESULTS: SARS-CoV-2-specific IgG antibodies, and also NAb can persist among over 95% COVID-19 convalescents from 6 months to 12 months after disease onset. At least 19/71 (26%) of COVID-19 convalescents (double positive in ELISA and MCLIA) had detectable circulating IgM antibody against SARS-CoV-2 at 12m post-disease onset. Notably, the percentages of convalescents with positive SARS-CoV-2-specific T-cell responses (at least one of the SARS-CoV-2 antigen S1, S2, M and N protein) were 71/76 (93%) and 67/73 (92%) at 6m and 12m, respectively. Furthermore, both antibody and T-cell memory levels of the convalescents were positively associated with their disease severity. CONCLUSIONS: SARS-CoV-2-specific cellular and humoral immunities are durable at least until one year after disease onset.
\n \n\n \n \nBACKGROUND: Typhoid fever is a major public health problem in low-resource settings. Vaccination can help curb the disease and might reduce transmission. We have previously reported an interim analysis of the efficacy of typhoid conjugate vaccine (TCV) in Nepali children. Here we report the final results after 2 years of follow-up. METHODS: We did a participant-masked and observer-masked individually randomised trial in Lalitpur, Nepal, in which 20\u2008019 children aged 9 months to younger than 16 years were randomly assigned in a 1:1 ratio to receive a single dose of TCV (Typbar TCV, Bharat Biotech International, India) or capsular group A meningococcal conjugate vaccine (MenA). Participants were followed up until April 9, 2020. The primary outcome was blood culture-confirmed typhoid fever. Cases were captured via passive surveillance and active telephone surveillance followed by medical record review. The trial is registered at ISRCTN registry, ISRCTN43385161 and is ongoing. FINDINGS: From Nov 20, 2017, to April 9, 2018, of 20\u2008119 children screened, 20\u2008019 participants were randomly assigned to receive TCV or MenA vaccine. There were 75 cases of blood culture-confirmed typhoid fever included in the analysis (13 in the TCV group and 62 in the MenA group) over the 2-year period. The protective efficacy of TCV against blood culture-confirmed typhoid fever at 2 years was 79\u00b70% (95% CI 61\u00b79-88\u00b75; p<0\u00b70001). The incidence of typhoid fever was 72 (95% CI 38-123) cases per 100\u2008000 person-years in the TCV group and 342 (95% CI 262-438) cases per 100\u2008000 person-years in the MenA group. Adverse events occurring within the first 7 days post-vaccination were reported previously. INTERPRETATION: The final results of this randomised, controlled trial are in keeping with the results of our published interim analysis. There is no evidence of waning protection over a 2-year period. These findings add further support for the WHO recommendations on control of enteric fever. FUNDING: Bill & Melinda Gates Foundation.
\n \n\n \n \nINTRODUCTION: The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses. METHODS: RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in S\u00e3o Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer-BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18-60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0\u00b767. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Cl\u00ednicos, number RBR-9nn3scw. FINDINGS: Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20\u00b74% (95% CI 12\u00b78-30\u00b71) in adults aged 18-60 years and 8\u00b79% (4\u00b72-16\u00b72) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67-88) for Ad26.COV2-S, 152 (134-173) for BNT162b2, 90 (77-104) for ChAdOx1 nCoV-19, and 12 (11-14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6\u00b77 (95% CI 5\u00b78-7\u00b77) for Ad26.COV2-S, 13\u00b74 (11\u00b76-15\u00b73) for BNT162b2, and 7\u00b70 (6\u00b71-8\u00b71) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8\u00b77 (95% CI 5\u00b79-12\u00b79) for Ad26.COV2-S vaccine, 21\u00b75 (14\u00b75-31\u00b79) for BNT162b2, and 10\u00b76 (7\u00b72-15\u00b76) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home. INTERPRETATION: Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. FUNDING: Ministry of Health, Brazil.
\n \n\n \n \nThe impacts of healthcare professionals (HCPs) being research participants are often neglected. As professionals, they tend to be perceived as \u2018immune\u2019 to many negative effects of sharing their experiences. However, in the context of an ongoing global pandemic such as COVID-19, these assumptions can be clearly challenged. This article draws on researchers\u2019 experiences of conducting single and longitudinal qualitative interviews with HCPs during the COVID-19 pandemic in Europe during 2020. Reflecting on the methodological and ethical implications of doing such research during a pandemic allows researchers to surface assumptions about and question categories of \u2018vulnerability\u2019 and \u2018sensitivity\u2019. We explore these categories in relation to three issues we have identified: (i) Blurred boundaries in researcher-participant relationships; (ii) Interviews as spaces to process experiences; and (iii) Motivations to conduct and participate in research. We demonstrate that qualitative interviews during a pandemic are embedded in sense-making processes for both the interviewer and participant, and as such may play an important role in coping and resilience. We therefore argue for ethically active research that critically engages with the concepts of \u2018vulnerability\u2019 and \u2018sensitivity\u2019, and underpinning assumptions, in context over time throughout the research process for current and future research with HCPs and other groups beyond pandemic situations. We thus aim to prepare researchers for managing these potential facets during the research process. We conclude with practical implications for managing emerging ethical tensions, methodological challenges and the wide-ranging possibilities and responsibilities for research with HCPs, urging researchers to consider the issues in advance.
\n \n\n \n \nCytomegalovirus (CMV) is a globally ubiquitous pathogen with a seroprevalence of approximately 50% in the UK. CMV infection induces expansion of immunosenescent T cell and NK cell populations with these cells demonstrating lower responsiveness to activation and reduced functionality upon infection and vaccination. In this study, we found that CMV+ participants had normal T cell responses after single dose or homologous vaccination with the viral vector ChAdOx1. In contrast, CMV seropositivity was associated with a loss of T cell IFN-\u03b3 secretion following heterologous ChAd-MVA viral vector vaccination. Analysis of participants receiving a single dose of ChAdOx1 demonstrates that T cells from CMV+ donors have a more terminally differentiated profile of CD57+PD1+ CD4+ T cells and CD8+ T cells expressing less IL-2R\u03b1 (CD25), and fewer polyfunctional CD4+ T cells 14 days post-vaccination. NK cells from CMV-seropositive individuals also have a reduced activation profile. Overall, our data suggest that although CMV infection enhances immunosenescence of T and NK populations, it does not affect antigen-specific T cell IFN-\u03b3 secretion or antibody IgG production after vaccination with the current ChAdOx1 nCoV-19 vaccination regimen in the UK.
\n \n\n \n \nChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenovirus\u00e2\u20ac\"vectored vaccine encoding the spike (S) protein of SARS-CoV-2, based on the first published full-length sequence (Wuhan-1). AZD1222 was shown to have 74% vaccine efficacy (VE) against symptomatic disease in clinical trials and over 2.5 billion doses of vaccine have been released for worldwide use. However, SARS-CoV-2 continues to circulate and consequently, variants of concern (VoCs) have been detected, with substitutions in the S protein that are associated with a reduction in virus neutralizing antibody titer. Updating vaccines to include S proteins of VoCs may be beneficial over boosting with vaccines encoding the ancestral S protein, even though current real-world data is suggesting good efficacy against hospitalization and death following boosting with vaccines encoding the ancestral S protein. Using the Syrian hamster model, we evaluated the effect of a single dose of AZD2816, encoding the S protein of the Beta VoC, and efficacy of AZD1222/AZD2816 as a heterologous primary series against challenge with the Beta or Delta variant. We then investigated the efficacy of a single dose of AZD2816 or AZD1222 against the Omicron VoC. As seen previously, minimal to no viral sgRNA could be detected in lungs of vaccinated animals obtained at 5 days post inoculation, in contrast to lungs of control animals. Thus, these vaccination regimens are protective against the Beta, Delta, and Omicron VoCs in the hamster model.
\n \n\n \n \nBACKGROUND: Multidrug resistance and fluoroquinolone non-susceptibility (FQNS) are major concerns for the epidemiology and treatment of typhoid fever. The 2018 prequalification of the first typhoid conjugate vaccine (TCV) by WHO provides an opportunity to limit the transmission and burden of antimicrobial-resistant typhoid fever. METHODS: We combined output from mathematical models of typhoid transmission with estimates of antimicrobial resistance from meta-analyses to predict the burden of antimicrobial-resistant typhoid fever across 73 lower-income countries eligible for support from Gavi, the Vaccine Alliance. We considered FQNS and multidrug resistance separately. The effect of vaccination was predicted on the basis of forecasts of vaccine coverage. We explored how the potential effect of vaccination on the prevalence of antimicrobial resistance varied depending on key model parameters. FINDINGS: The introduction of routine immunisation with TCV at age 9 months with a catch-up campaign up to age 15 years was predicted to avert 46-74% of all typhoid fever cases in 73 countries eligible for Gavi support. Vaccination was predicted to reduce the relative prevalence of antimicrobial-resistant typhoid fever by 16% (95% prediction interval [PI] 0-49). TCV introduction with a catch-up campaign was predicted to avert 42\u00b75 million (95% PI 24\u00b78-62\u00b78 million) cases and 506\u2009000 (95% PI 187\u2009000-1\u00b79 million) deaths caused by FQNS typhoid fever, and 21\u00b72 million (95% PI 16\u00b74-26\u00b75 million) cases and 342\u2009000 (95% PI 135\u2009000-1\u00b75 million) deaths from multidrug-resistant typhoid fever over 10 years following introduction. INTERPRETATION: Our results indicate the benefits of prioritising TCV introduction for countries with a high avertable burden of antimicrobial-resistant typhoid fever. FUNDING: The Bill & Melinda Gates Foundation.
\n \n\n \n \nBackground: Non-typhoidal salmonella can cause serious, life-threatening invasive infections involving the bloodstream and other normally sterile sites. We aimed to systematically review the prevalence of complications and case-fatality ratio (CFR) of non-typhoidal salmonella invasive disease to provide contemporary global estimates and inform the development of vaccine and non-vaccine interventions. Methods: We did a global systematic review and meta-analysis of studies investigating the complications and mortality associated with non-typhoidal salmonella invasive disease. We searched Embase, MEDLINE, Web of Science, and PubMed for peer-reviewed, primary research articles published from database inception up to June 4, 2021, with no restrictions on language, country, date, or participant demographics. Only studies reporting the proportion of complications or deaths associated with non-typhoidal salmonella invasive disease, confirmed by culture of samples taken from a normally sterile site (eg, blood or bone marrow) were included. We excluded case reports, case series, policy reports, commentaries, editorials, and conference abstracts. Data on the prevalence of complications and CFR were abstracted. The primary outcomes were to estimate the prevalence of complications and CFR of non-typhoidal salmonella invasive disease. We calculated an overall pooled CFR estimate and pooled CFR stratified by UN region, subregion, age group, and by serovar when available with a random-effects meta-analysis. A risk-of-bias assessment was done, and heterogeneity was assessed with Cochran's Q Test, I2, and \u03c42. This study was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and is registered with PROSPERO, CRD42020202293. Findings: The systematic review returned a total of 8770 records. After duplicates were removed, 5837 titles and abstracts were screened, yielding 84 studies from 35 countries after exclusions. Of these included studies, 77 (91\u00b77%) were hospital-based and 66 (78\u00b76%) were located in Africa or Asia. Among 55 studies reporting non-typhoidal salmonella disease-associated complications, a total of 45 different complications were reported and 1824 complication events were identified among 6974 study participants. The most prevalent complication was septicaemia, occurring in 171 (57\u00b72%) of 299 participants, followed by anaemia in 580 (47\u00b73%) of 1225 participants. From 81 studies reporting the CFR of non-typhoidal salmonella invasive disease, the overall pooled CFR estimate was 14\u00b77% (95% CI 12\u00b72\u201317\u00b73). When stratified by UN region, the pooled CFR was 17\u00b71% (13\u00b76\u201321\u00b70) in Africa, 14\u00b70% (9\u00b74\u201319\u00b74) in Asia, 9\u00b79% (6\u00b74\u201314\u00b70) in Europe, and 9\u00b76% (0\u00b70\u201325\u00b71) in the Americas. Of all 84 studies, 66 (78\u00b76%) had an overall high risk of bias, 18 (21\u00b74%) had a moderate risk, and none had a low risk. Substantial heterogeneity (I2>80%) was observed in most (15 [65\u00b72%] of 23) CFR estimates. Interpretation: Complications were frequent among individuals with non-typhoidal salmonella invasive disease and approximately 15% of patients died. Clinicians, especially in African countries, should be aware of non-typhoidal salmonella invasive disease as a cause of severe febrile illness. Prompt diagnoses and management decisions, including empiric antimicrobial therapy, would improve patient outcomes. Additionally, investments in improving clinical microbiology facilities to identify non-typhoidal salmonella and research efforts towards vaccine development and non-vaccine prevention measures would prevent non-typhoidal salmonella invasive disease-associated illness and death. Funding: EU Horizon 2020 research and innovation programme.
\n \n\n \n \nOBJECTIVES: While there is research relating to perceptions of vaccines among healthcare workers (HCWs), the evidence base in relation to COVID-19 remains limited. The aim of this study was to explore HCWs' perceptions and attitudes towards vaccines and the COVID-19 vaccination programme in the UK, including their expectations and views on promoting vaccination to others. DESIGN: This study was designed as a rapid qualitative appraisal, integrating data from a review of UK policies and guidance on COVID-19 vaccination with data from in-depth semistructured telephone interviews with frontline HCWs in the UK. Data were analysed using framework analysis. PARTICIPANTS: Interviews were carried out with a purposive sample of HCWs from two large London-based hospital Trusts (n=24) and 24 government policies, and guidelines on the vaccination programme were reviewed. RESULTS: The level of uncertainty about the long-term safety of vaccines and efficacy against mutant strains made it difficult for HCWs to balance the benefits against the risks of vaccination. HCWs felt that government decisions on vaccine rollout had not been supported by evidence-based science, and this impacted their level of trust and confidence in the programme. The spread of misinformation online also impacted HCWs' attitudes towards vaccination, particularly among junior level and black, Asian and minority ethnic (BAME) HCWs. Most HCWs felt encouraged to promote vaccination to their patients, and the majority said they would advocate vaccination or engage in conversations about vaccination with others when relevant. CONCLUSION: In order to improve HCWs' trust and confidence in the UK's COVID-19 vaccination programme, there needs to be clarity about what is known and not known about the vaccines and transparency around the evidence-base supporting government decisions on vaccine rollout. Effort is also needed to dispel the spread of vaccine-related misinformation online and to address specific concerns, particularly among BAME and junior-level HCWs.
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