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1.
J Thromb Haemost ; 2023 May 23.
Article in English | MEDLINE | ID: covidwho-2323979

ABSTRACT

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

3.
J Infect ; 87(1): 18-26, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2299003

ABSTRACT

BACKGROUND: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. METHODS: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer-BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. RESULTS: Among the 817 participants included in this report, the median age was 72 years (IQR: 55-78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. CONCLUSIONS: Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns.


Subject(s)
COVID-19 , Viral Vaccines , Female , Humans , Aged , Male , COVID-19 Vaccines , BNT162 Vaccine , ChAdOx1 nCoV-19 , COVID-19/prevention & control , SARS-CoV-2 , Immunity , United Kingdom , Immunoglobulin G , Antibodies, Viral , Vaccination , Immunogenicity, Vaccine
4.
Lancet Infect Dis ; 2022 Oct 04.
Article in English | MEDLINE | ID: covidwho-2232664

ABSTRACT

BACKGROUND: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. METHODS: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243. FINDINGS: 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality. INTERPRETATION: The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse. FUNDING: UK National Institute for Health and Care Research.

5.
Clin Med (Lond) ; 22(6): 586-589, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2145157

ABSTRACT

In its first 2 decades, the NHS witnessed the near eradication of life-threatening community-acquired infections. However, medical advances have created different challenges (such as antimicrobial resistance and healthcare-associated infections) against a background of an increasingly ageing population. The recent COVID-19 pandemic has highlighted a lack of parity with regards to provision of NHS 'infection services' (infectious diseases, microbiology and virology) across the UK, which urgently needs to be addressed. We recommend a fundamental review of NHS infection service provision: divided into four key areas. Firstly, there should be a consideration of a single multidisciplinary specialty of infection medicine removing barriers to training and service delivery. Secondly, streamline infection training via a single pathway through to certificate of completion of training, encompassing all aspects of infection service provision, for example, infection diagnostics, clinical care (including inpatient, outpatient and community based care), and infection prevention and control. There should be flexibility within the training curriculum to facilitate combined training with general internal medicine (GIM) as well as out of programme activities. Innovative ways of providing clinical experience should be considered, acknowledging the roles that medical microbiologists working closely with GIM colleagues in district general hospitals can play in managing patients with infections. Thirdly, formally commission a national network of specialised infectious diseases units with the creation of service standards. This can facilitate future pandemic resilience using a hub-and-spoke model utilising local infection expertise. Lastly, standardise the NHS framework to lead and coordinate development of integrated infection services at the local level.


Subject(s)
COVID-19 , Communicable Diseases , Humans , Pandemics , State Medicine , Curriculum
6.
Methods Protoc ; 5(6)2022 Nov 28.
Article in English | MEDLINE | ID: covidwho-2123765

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health. Procalcitonin (PCT) is an inflammatory marker measured in blood samples and widely recommended to help diagnose bacterial infections and guide antibiotic treatment. The PEACH study will compare patient outcomes from English and Welsh hospitals that used PCT testing during the first wave of the COVID-19 pandemic with those from hospitals not using PCT. It will help to determine whether, and how, PCT testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. PEACH is a retrospective observational cohort study using patient-level clinical data from acute hospital Trusts and Health Boards in England and Wales. The primary objective is to measure the difference in antibiotic use between COVID-19 patients who did or did not have PCT testing at the time of diagnosis. Secondary objectives include measuring differences in length of stay, mortality, intensive care unit admission, and resistant bacterial infections between these groups.

8.
Lancet Infect Dis ; 22(8): 1131-1141, 2022 08.
Article in English | MEDLINE | ID: covidwho-1946941

ABSTRACT

BACKGROUND: Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19. METHODS: The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (anti-spike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing. FINDINGS: Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6-77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3-214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030-27 162), which increased to 37 460 ELU/mL (31 996-43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41-1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996-30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826-64 452), with a geometric mean fold change of 2·19 (1·90-2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37-14·32) and 15·90 (12·92-19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24-16·54] in the BNT162b2 group and 6·22 [3·90-9·92] in the mRNA-1273 group). INTERPRETATION: Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose. FUNDING: UK Vaccine Task Force and National Institute for Health Research.


Subject(s)
COVID-19 Vaccines , COVID-19 , 2019-nCoV Vaccine mRNA-1273 , Aged , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Female , Humans , Immunogenicity, Vaccine , Immunoglobulin G , Male , Middle Aged , SARS-CoV-2
9.
JAC-antimicrobial resistance ; 4(Suppl 1), 2022.
Article in English | EuropePMC | ID: covidwho-1823913

ABSTRACT

Background A minority of patients presenting to hospital with COVID-19 have bacterial coinfection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. The PEACH study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic to help diagnose bacterial infections and guide antibiotic treatment. There is a lack of clear evidence to support its use in lung infections, which means in some hospitals, clinicians have used the procalcitonin test to guide antibiotic decisions in COVID-19, whilst in other hospitals, they have not. Our study is analysing data from hospitals that did and did not use procalcitonin testing during the first wave of the COVID-19 pandemic. It will determine whether and how procalcitonin testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. Methods To assess whether the use of PCT testing, to guide antibiotic prescribing, safely reduced antibiotic use among patients who were hospitalized with COVID-19 during the first wave of the pandemic, we are answering this question through three different, and complimentary, work streams (WS), each with discrete work packages (WP): (i) Work Stream 1: utilization of PCT testing to guide antibiotic prescribing during the first wave of COVID-19 pandemic;(ii) Work Stream 2: patient-level impact of PCT testing on antibiotic exposure and clinical outcome (main work stream currently in analysis);and (iii) Work Stream 3: health economics analysis of PCT testing to guide antibiotics in COVID-19. Results Our first publication from Work Stream 1 (Antibiotics 2021, 10: 516) used a web-based survey to gather data from antimicrobial leads about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in ICU increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empirical antibiotic cessation and guidance about interpretation of values. Conclusions Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety. Work Stream 2 is ongoing, and results will be published once available.

10.
J Infect ; 84(6): 795-813, 2022 06.
Article in English | MEDLINE | ID: covidwho-1778315

ABSTRACT

OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 µg) or BNT (30 µg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 µg) versus BNT (30 µg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.


Subject(s)
COVID-19 , Viral Vaccines , Ad26COVS1 , Adult , Aged , Aged, 80 and over , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , ChAdOx1 nCoV-19 , Humans , Immunogenicity, Vaccine , Immunoglobulin G , Middle Aged , SARS-CoV-2 , United Kingdom , mRNA Vaccines
11.
J Antimicrob Chemother ; 77(4): 1189-1196, 2022 03 31.
Article in English | MEDLINE | ID: covidwho-1684714

ABSTRACT

BACKGROUND: Blood biomarkers have the potential to help identify COVID-19 patients with bacterial coinfection in whom antibiotics are indicated. During the COVID-19 pandemic, procalcitonin testing was widely introduced at hospitals in the UK to guide antibiotic prescribing. We have determined the impact of this on hospital-level antibiotic consumption. METHODS: We conducted a retrospective, controlled interrupted time series analysis of organization-level data describing antibiotic dispensing, hospital activity and procalcitonin testing for acute hospitals/hospital trusts in England and Wales during the first wave of COVID-19 (24 February to 5 July 2020). RESULTS: In the main analysis of 105 hospitals in England, introduction of procalcitonin testing in emergency departments/acute medical admission units was associated with a statistically significant decrease in total antibiotic use of -1.08 (95% CI: -1.81 to -0.36) DDDs of antibiotic per admission per week per trust. This effect was then lost at a rate of 0.05 (95% CI: 0.02-0.08) DDDs per admission per week. Similar results were found specifically for first-line antibiotics for community-acquired pneumonia and for COVID-19 admissions rather than all admissions. Introduction of procalcitonin in the ICU setting was not associated with any significant change in antibiotic use. CONCLUSIONS: At hospitals where procalcitonin testing was introduced in emergency departments/acute medical units this was associated with an initial, but unsustained, reduction in antibiotic use. Further research should establish the patient-level impact of procalcitonin testing in this population and understand its potential for clinical effectiveness.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Procalcitonin , Anti-Bacterial Agents/therapeutic use , COVID-19/diagnosis , Hospitals , Humans , Interrupted Time Series Analysis , Pandemics , Retrospective Studies , State Medicine , United Kingdom
12.
Lancet ; 398(10318): 2258-2276, 2021 12 18.
Article in English | MEDLINE | ID: covidwho-1550152

ABSTRACT

BACKGROUND: Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT). METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY)control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130. FINDINGS: Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273. INTERPRETATION: All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination. FUNDING: UK Vaccine Taskforce and National Institute for Health Research.


Subject(s)
BNT162 Vaccine/administration & dosage , COVID-19/prevention & control , ChAdOx1 nCoV-19/administration & dosage , Immunization, Secondary/methods , Immunogenicity, Vaccine , Adult , Aged , Aged, 80 and over , BNT162 Vaccine/immunology , COVID-19/immunology , ChAdOx1 nCoV-19/immunology , Female , Humans , Male , Middle Aged , Pandemics , Patient Safety , SARS-CoV-2 , United Kingdom
13.
BMJ Open ; 11(6): e046799, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1276961

ABSTRACT

INTRODUCTION: There is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications. METHODS AND ANALYSIS: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomised clinical trial to evaluate potential treatments for COVID-19 in the community. A master protocol governs the addition of new interventions as they become available, as well as the inclusion and cessation of existing intervention arms via frequent interim analyses. The first three interventions are hydroxychloroquine, azithromycin and doxycycline. Eligible participants must be symptomatic in the community with possible or confirmed COVID-19 that started in the preceding 14 days and either (1) aged 65 years and over or (2) aged 50-64 years with comorbidities. Recruitment is through general practice, health service helplines, COVID-19 'hot hubs' and directly through the trial website. Participants are randomised to receive either usual care or a study drug plus usual care, and outcomes are collected via daily online symptom diary for 28 days from randomisation. The research team contacts participants and/or their study partner following days 7, 14 and 28 if the online diary is not completed. The trial has two coprimary endpoints: time to first self-report of feeling recovered from possible COVID-19 and hospital admission or death from possible COVID-19 infection, both within 28 days from randomisation. Prespecified interim analyses assess efficacy or futility of interventions and to modify randomisation probabilities that allocate more participants to interventions with better outcomes. ETHICS AND DISSEMINATION: Ethical approval Ref: 20/SC/0158 South Central - Berkshire Research Ethics Committee; IRAS Project ID: 281958; EudraCT Number: 2020-001209-22. Results will be presented to policymakers and at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN86534580.


Subject(s)
COVID-19 , Aged , Humans , Hydroxychloroquine , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
14.
Antibiotics (Basel) ; 10(5)2021 May 01.
Article in English | MEDLINE | ID: covidwho-1223911

ABSTRACT

A minority of patients presenting to hospital with COVID-19 have bacterial co-infection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. This study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic. A web-based survey of antimicrobial leads gathered data about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in Intensive Care Units (ICU) increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empiric antibiotic cessation and guidance about interpretation of values. Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety.

15.
J Med Microbiol ; 70(4)2021 Apr.
Article in English | MEDLINE | ID: covidwho-1189541

ABSTRACT

Introduction. During previous viral pandemics, reported co-infection rates and implicated pathogens have varied. In the 1918 influenza pandemic, a large proportion of severe illness and death was complicated by bacterial co-infection, predominantly Streptococcus pneumoniae and Staphylococcus aureus.Gap statement. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship.Aim. To describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England.Methodology. A retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at <48 and >48 h following hospital admission, corresponding to community and hospital-acquired co-infections.Results. Of 254 patients studied (median age 59 years (IQR 49-69); 64.6 % male), 139 clinically significant organisms were identified from 83 (32.7 %) patients. Bacterial co-infections/ co-colonisation were identified within 48 h of admission in 14 (5.5 %) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli. The co-infection/ co-colonisation rate >48 h after admission was 27/1000 person-days (95 % CI 21.3-34.1). Patients with co-infections/ co-colonisation were more likely to die in ICU (crude OR 1.78,95 % CI 1.03-3.08, P=0.04) compared to those without co-infections/ co-colonisation.Conclusion. We found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.


Subject(s)
Bacterial Infections/epidemiology , COVID-19/epidemiology , Coinfection/epidemiology , Adult , Aged , Aged, 80 and over , Bacteria/classification , Bacteria/isolation & purification , Bacterial Infections/microbiology , COVID-19/microbiology , Coinfection/microbiology , Critical Illness , Cross Infection/epidemiology , Cross Infection/microbiology , England/epidemiology , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Odds Ratio , Retrospective Studies , SARS-CoV-2 , Young Adult
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