Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336247

ABSTRACT

Objective To analyse the impact on hospital admissions for COVID-19 of large-scale, voluntary, public open access rapid testing for SARS-CoV-2 antigen in Liverpool (UK) between 6 th November 2020 and 2 nd January 2021. Design Synthetic control analysis comparing hospital admissions for small areas in the intervention population to a group of control areas weighted to be similar in terms of prior COVID-19 hospital admission rates and socio-demographic factors. Intervention COVID-SMART (Systematic Meaningful Asymptomatic Repeated Testing), a national pilot of large-scale, voluntary rapid antigen testing for people without symptoms of COVID-19 living or working in the City of Liverpool, deployed with the assistance of the British Army from the 6 th November 2020 in an unvaccinated population. This pilot informed the UK roll-out of SARS-CoV-2 antigen rapid testing, and similar policies internationally. Main outcome measure Weekly COVID-19 hospital admissions for neighbourhoods in England. Results The intensive introduction of COVID-SMART community testing was associated with a 43% (95% confidence interval: 29% to 57%) reduction in COVID-19 hospital admissions in Liverpool compared to control areas for the initial period of intensive testing with military assistance in national lockdown from 6 th November to 3 rd December 2020. A 25% (11% to 35%) reduction was estimated across the overall intervention period (6 th November 2020 to 2 nd January 2021), involving fewer testing centres, before England’s national roll-out of community testing, after adjusting for regional differences in Tiers of COVID-19 restrictions from 3 rd December 2020 to 2 nd January 2021. Conclusions The world’s first voluntary, city-wide SARS-CoV-2 rapid antigen testing pilot in Liverpool substantially reduced COVID-19 hospital admissions. Large scale asymptomatic rapid testing for SARS-CoV-2 can help reduce transmission and prevent hospital admissions. Summary box What is already known on this topic – Previous studies on managing the spread of SARS-CoV-2 have identified asymptomatic transmission as significant challenges for controlling the pandemic. – Along with non-pharmaceutical measures, many countries rolled out population-based asymptomatic testing programmes to further limit transmission. – Evidence is required on whether large scale voluntary testing of communities for COVID-19 reduces severe disease, by breaking chains of transmission. What this study adds – The findings of this study suggest that large scale rapid antigen testing of communities for SARS-CoV-2, within an agile local public health campaign, can reduce transmission and prevent hospital admissions. – The results indicate that policy makers should integrate such testing into comprehensive, local public health programmes targeting high risk groups, supporting those required to isolate and adapting promptly to prevailing biological, behavioural and environmental circumstances.

3.
Frontiers in nutrition ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1837226

ABSTRACT

Background Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which since 2019 has caused over 5 million deaths to date. The pathogenicity of the virus is highly variable ranging from asymptomatic to fatal. Evidence from experimental and observational studies suggests that circulating micronutrients may affect COVID-19 outcomes. Objectives To complement and inform observational studies, we investigated the associations of genetically predicted concentrations of 12 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, vitamin D, and zinc) with SARS-CoV-2 infection risk and COVID-19 severity using Mendelian randomization (MR). Methods Two-sample MR was conducted using 87,870 individuals of European descent with a COVID-19 diagnosis and 2,210,804 controls from the COVID-19 host genetics initiative. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Results Compared to the general population, nominally significant associations were noted for higher genetically predicted vitamin B-6 (Odds ratio per standard deviation [ORSD]: 1.06;95% confidence interval [CI]: 1.00, 1.13;p-value = 0.036) and lower magnesium concentrations (ORSD: 0.33;95%CI: 0.11, 0.96;P = 0.042) with COVID-19 infection risk. However, the association for magnesium was not consistent in some sensitivity analyses, and sensitivity analyses could not be performed for vitamin B-6 as only two genetic instruments were available. Genetically predicted levels of calcium, folate, β-carotene, copper, iron, vitamin B-12, vitamin D, selenium, phosphorus, or zinc were not associated with the outcomes from COVID-19 disease. Conclusion These results, though based only on genetically predicated circulating micronutrient concentrations, provide scant evidence for possible associations of micronutrients with COVID-19 outcomes.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332878

ABSTRACT

Objective To examine if SARS-CoV-2 infections vary by vaccination status, if an individual had previously tested positive and by neighbourhood socioeconomic deprivation across the Delta and Omicron epidemic waves of SARS-CoV-2. Design Cohort study using electronic health records Setting Cheshire and Merseyside, England (3 rd June 2021 to 1 st March 2022) Participants 2.7M residents Main Outcome measure Registered positive test for SARS-CoV-2 Results Social inequalities in registered positive tests were dynamic during the study. Originally higher SARS-CoV-2 rates in the most socioeconomically deprived neighbourhoods changed to being higher in the least deprived neighbourhoods from the 1 st September 2021. While the introduction of Omicron initially reset inequalities, they continued to be dynamic and inconsistent. Individuals who were fully vaccinated (two doses) were associated with fewer registered positive tests (e.g., between 1 st September and 27 th November 2021: (i) individuals engaged in testing – Hazards Ratio (HR) = 0.48, 95% Confidence Intervals (CIs) = 0.47-0.50;(ii) individuals engaged with healthcare - HR = 0.34, 95% CIs = 0.33-0.34). Individuals with a previous registered positive test were also less likely to have a registered positive test (e.g., between 1 st September and 27 th November 2021: (i) individuals engaged in testing - HR = 0.16, 95% CIs = 0.15-0.18;(ii) individuals engaged with healthcare - HR = 0.14, 95% CIs = 0.13-0.16). However, Omicron is disrupting these associations due to immune escape resulting in smaller effect sizes for both measures. Conclusions Changing patterns of SARS-CoV-2 infections during the Delta and Omicron waves reveals a dynamic pandemic that continues to affect diverse communities in sometimes unexpected ways.

5.
J Am Pharm Assoc (2003) ; 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1768260

ABSTRACT

On March 4, 2022, the American Medical Association (AMA) released a statement in response to the Biden administration's plan of a test-to-treat plan allowing pharmacists to serve as locations to test and provide prescriptions for oral antiviral therapies for the treatment of coronavirus disease 2019 (COVID-19) after a positive test result. The statement by AMA contradicts and underrepresents the impact pharmacists have on clinical practice. Pharmacists have been a crucial part of many efforts including mass vaccination efforts and furnishing of prescriptions for other complex disease states (e.g., pre-exposure prophylaxis and postexposure prophylaxis therapy). Furthermore, health systems have proven that novel approaches to mitigate operational and clinical barriers to COVID-19 therapies may offset the increased demand needed by communities. Herein, this commentary will discuss a viewpoint and counterpoint to the statement put out by AMA, with a focus on pharmacists.

6.
BMC Infect Dis ; 22(1): 270, 2022 Mar 20.
Article in English | MEDLINE | ID: covidwho-1745481

ABSTRACT

BACKGROUND: From January to May 2021 the alpha variant (B.1.1.7) of SARS-CoV-2 was the most commonly detected variant in the UK. Following this, the Delta variant (B.1.617.2) then became the predominant variant. The UK COVID-19 vaccination programme started on 8th December 2020. Prior to the Delta variant, most vaccine effectiveness studies focused on the alpha variant. We therefore aimed to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech) and the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in preventing symptomatic and asymptomatic infection with respect to the Delta variant in a UK setting. METHODS: We used anonymised public health record data linked to infection data (PCR) using the Combined Intelligence for Population Health Action resource. We then constructed an SIR epidemic model to explain SARS-CoV-2 infection data across the Cheshire and Merseyside region of the UK. Vaccines were assumed to be effective after 21 days for 1 dose and 14 days for 2 doses. RESULTS: We determined that the effectiveness of the Oxford-AstraZeneca vaccine in reducing susceptibility to infection is 39% (95% credible interval [34, 43]) and 64% (95% credible interval [61, 67]) for a single dose and a double dose respectively. For the Pfizer-BioNTech vaccine, the effectiveness is 20% (95% credible interval [10, 28]) and 84% (95% credible interval [82, 86]) for a single-dose and a double dose respectively. CONCLUSION: Vaccine effectiveness for reducing susceptibility to SARS-CoV-2 infection shows noticeable improvement after receiving two doses of either vaccine. Findings also suggest that a full course of the Pfizer-BioNTech provides the optimal protection against infection with the Delta variant. This reinforces the need to complete the full course programme to maximise individual protection and reduce transmission.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2/genetics
7.
Front Immunol ; 13: 851620, 2022.
Article in English | MEDLINE | ID: covidwho-1731787

ABSTRACT

Myocarditis and myopericarditis may occur after COVID-19 vaccination with an incidence of two to twenty cases per 100,000 individuals, but underlying mechanisms related to disease onset and progression remain unclear. Here, we report a case of myopericarditis following the first dose of the mRNA-1273 COVID-19 vaccine in a young man who had a history of mild COVID-19 three months before vaccination. The patient presented with chest pain, elevated troponin I level, and electrocardiogram abnormality. His endomyocardial biopsy revealed diffuse CD68+ cell infiltration. We characterized the immune profile of the patient using multiplex cytokine assay and flow cytometry analysis. Sex-matched vaccinated individuals and healthy individuals were used as controls. IL-18 and IL-27, Th1-type cytokines, were highly increased in the patient with COVID-19 vaccine-related myopericarditis compared with vaccinated controls who experienced no cardiac complications. In the patient, circulating NK cells and T cells showed an activated phenotype and mRNA profile, and monocytes expressed increased levels of IL-18 and its upstream NLRP3 inflammasome. We found that recombinant IL-18 administration into mice caused mild cardiac dysfunction and activation of NK cells and T cells in the hearts, similar to the findings in the patient with myopericarditis after COVID-19 mRNA vaccination. Collectively, myopericarditis following COVID-19 mRNA vaccination may be associated with increased IL-18-mediated immune responses and cardiotoxicity.


Subject(s)
/adverse effects , COVID-19/immunology , Immunity/immunology , Interleukin-18/immunology , Myocarditis/chemically induced , Vaccination/adverse effects , Adult , Animals , Humans , Killer Cells, Natural/immunology , Male , Mice , SARS-CoV-2/immunology , Young Adult
8.
J Sci Med Sport ; 23(7): 664-669, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1720500

ABSTRACT

The purpose of testing for any communicable disease is to support clinicians in the diagnosis and management of individual patients and to describe transmission dynamics. The novel coronavirus is formally named SARS-CoV-2 and the clinical disease state resulting from an infection is known as COVID-19. Control of the COVID-19 pandemic requires clinicians, epidemiologists, and public health officials to utilise the most comprehensive, accurate and timely information available to manage the rapidly evolving COVID-19 environment. High performance sport is a unique context that may look towards comprehensive testing as a means of risk mitigation. Characteristics of the common testing options are discussed including the circumstances where additional testing may be of benefit and considerations for the associated risks. Finally, a review of the available technology that could be considered for use by medical staff at the point of care (PoC) in a high-performance sporting context is included.


Subject(s)
Clinical Laboratory Techniques/standards , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Sports , Australia , Betacoronavirus , COVID-19 , COVID-19 Testing , Humans , Pandemics , Point-of-Care Testing , SARS-CoV-2
9.
J Sci Med Sport ; 23(7): 639-663, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1720499

ABSTRACT

Sport makes an important contribution to the physical, psychological and emotional well-being of Australians. The economic contribution of sport is equivalent to 2-3% of Gross Domestic Product (GDP). The COVID-19 pandemic has had devastating effects on communities globally, leading to significant restrictions on all sectors of society, including sport. Resumption of sport can significantly contribute to the re-establishment of normality in Australian society. The Australian Institute of Sport (AIS), in consultation with sport partners (National Institute Network (NIN) Directors, NIN Chief Medical Officers (CMOs), National Sporting Organisation (NSO) Presidents, NSO Performance Directors and NSO CMOs), has developed a framework to inform the resumption of sport. National Principles for Resumption of Sport were used as a guide in the development of 'the AIS Framework for Rebooting Sport in a COVID-19 Environment' (the AIS Framework); and based on current best evidence, and guidelines from the Australian Federal Government, extrapolated into the sporting context by specialists in sport and exercise medicine, infectious diseases and public health. The principles outlined in this document apply to high performance/professional, community and individual passive (non-contact) sport. The AIS Framework is a timely tool of minimum baseline of standards, for 'how' reintroduction of sport activity will occur in a cautious and methodical manner, based on the best available evidence to optimise athlete and community safety. Decisions regarding the timing of resumption (the 'when') of sporting activity must be made in close consultation with Federal, State/Territory and/or Local Public Health Authorities. The priority at all times must be to preserve public health, minimising the risk of community transmission.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , Return to Sport/standards , Sports , Australia , Basic Reproduction Number , Betacoronavirus , COVID-19 , Communicable Disease Control , Decision Making , Guidelines as Topic , Humans , Public Health , SARS-CoV-2
10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310909

ABSTRACT

Background: The Innova SARS-CoV-2 antigen rapid lateral flow test (LFT) offers fast detection of COVID-19 cases. This study assesses the performance of LFT in the general population attending asymptomatic testing centres.Methods: Observational cohort study to compare LFT with reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) results based on two self-administrated swab samples per participant taken within minutes among individuals declaring no classic symptoms, attending asymptomatic testing sites in Liverpool, UK, between 6th and 29th of November 2020.Findings: 5869 individuals attended 48 testing sites in Liverpool. The relative sensitivity of LFT versus RT-qPCR, excluding void tests, was 40∙0% (95% CI: 28∙5 to 52∙4;28/70). The specificity was 99∙9% (99∙8 to 99∙99;5431/5434), positive predictive value was 90∙3% (74∙2 to 98∙0;28/31) and negative predictive value was 99∙2% (99∙0 to 99∙4;5431/5473). For cases with RT-qPCR cycle threshold CT <18∙3 (approximate viral loads > 10 6 RNA copies/ml), sensitivity was 90∙9% (58∙7 to 99∙8;10/11), for CT <24∙4 (viral load > 10 4 RNA copies/ml), sensitivity was 69∙4% (51∙9 to 83∙7;25/36), and for CT >24∙4 (viral load <10 4 RNA copies/ml), sensitivity was 9∙7% (1∙9 to 23∙7;3/34).Interpretation: Innova LFT is a helpful tool for identifying infections among people who declare no symptoms of COVID-19, particularly those with high viral load and so more likely to infect others. The number of cases with lower CT (indicating higher viral load) missed by LFT, although small, should be considered, with due caution over using single LFT in high-consequence settings. Clear and accurate communication with the public about how to interpret test results is important. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.Funding: This evaluation was commissioned by the UK Department of Health and Social Care.Declaration of Interests: This evaluation was commissioned by the UK Department of Health and Social Care. IEB, MGF, MGS, DMH, GB and CPC received grant funding from the UK Department of Health and Social Care to evaluate LFT in the Liverpool pilot discussed in this article. IEB reports fees from AstraZeneca as chief data scientist adviser via Liverpool University and a senior investigator grant from the National Institute for Health Research (NIHR) outside the submitted work. MGS is Chair of the Infectious Disease Scientific Advisory Board and a minority shareholder in Integrum Scientific LLC, Greensboro, NC, USA, a company that has interests in COVID-19 testing but not with lateral flow technology, and reports grants from the NIHR, the Medical Research Council, and the Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool.Ethics Approval Statement: The University of Liverpool provided secondary data analysis as part of a UK national service evaluation with data collection by the UK Department of Health and Social Care (DHSC;Sponsor) As per the National Health Service (NHS) Research Authority guidelines, this work did not require ethical approval.

11.
J Public Health (Oxf) ; 2022 Feb 04.
Article in English | MEDLINE | ID: covidwho-1684779

ABSTRACT

BACKGROUND: Twice weekly lateral flow tests (LFTs) for secondary school children was UK Government policy from 8 March 2021. We evaluate use of LFTs (both supervised at test centres, and home test kits) in school-aged children in Cheshire and Merseyside. METHODS: We report (i) number of LFT positives (ii) proportion of LFT positive with confirmatory reverse transcription polymerase chain reaction (PCR) test within 2 days, and (iii) agreement between LFT-positive and confirmatory PCR, and dependence of (i-iii) on COVID-19 prevalence. FINDINGS: 1 248 468 LFTs were taken by 211 255 12-18 years old, and 163 914 by 52 116 5-11 years old between 6 November 2020 and 31 July 2021. Five thousand three hundred and fourteen (2.5%) 12-18 years old and 1996 (3.8%) 5-11 years old returned LFT positives, with 3829 (72.1%) and 1535 (76.9%) confirmatory PCRs, and 3357 (87.7%) and 1383 (90.1%) confirmatory PCR-positives, respectively.Monthly proportions of LFT positive with PCR negative varied between 4.7% and 35.3% in 12-18 years old (corresponding proportion of all tests positive: 9.7% and 0.3%).Deprivation and non-White ethnicity were associated with reduced uptake of confirmatory PCR. INTERPRETATION: Substantial inequalities in confirmatory testing need more attention to avoid further disadvantage through education loss. When prevalence is low additional measures, including confirmatory testing, are needed. Local Directors of Public Health taking more control over schools testing may be needed. FUNDING: DHSC, MRC, NIHR, EPSRC.

12.
EBioMedicine ; 75: 103812, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1639102

ABSTRACT

BACKGROUND: Thromboembolism is a life-threatening manifestation of coronavirus disease 2019 (COVID-19). We investigated a dysfunctional phenotype of vascular endothelial cells in the lungs during COVID-19. METHODS: We obtained the lung specimens from the patients who died of COVID-19. The phenotype of endothelial cells and immune cells was examined by flow cytometry and immunohistochemistry (IHC) analysis. We tested the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the endothelium using IHC and electron microscopy. FINDINGS: The autopsy lungs of COVID-19 patients exhibited severe coagulation abnormalities, immune cell infiltration, and platelet activation. Pulmonary endothelial cells of COVID-19 patients showed increased expression of procoagulant von Willebrand factor (VWF) and decreased expression of anticoagulants thrombomodulin and endothelial protein C receptor (EPCR). In the autopsy lungs of COVID-19 patients, the number of macrophages, monocytes, and T cells was increased, showing an activated phenotype. Despite increased immune cells, adhesion molecules such as ICAM-1, VCAM-1, E-selectin, and P-selectin were downregulated in pulmonary endothelial cells of COVID-19 patients. Notably, decreased thrombomodulin expression in endothelial cells was associated with increased immune cell infiltration in the COVID-19 patient lungs. There were no SARS-CoV-2 particles detected in the lung endothelium of COVID-19 patients despite their dysfunctional phenotype. Meanwhile, the autopsy lungs of COVID-19 patients showed SARS-CoV-2 virions in damaged alveolar epithelium and evidence of hypoxic injury. INTERPRETATION: Pulmonary endothelial cells become dysfunctional during COVID-19, showing a loss of thrombomodulin expression related to severe thrombosis and infiltration, and endothelial cell dysfunction might be caused by a pathologic condition in COVID-19 patient lungs rather than a direct infection with SARS-CoV-2. FUNDING: This work was supported by the Johns Hopkins University, the American Heart Association, and the National Institutes of Health.


Subject(s)
Blood Coagulation Disorders/metabolism , COVID-19/metabolism , Down-Regulation , Endothelium, Vascular/metabolism , Hypoxia/metabolism , Lung/metabolism , SARS-CoV-2/metabolism , Thrombomodulin/biosynthesis , Aged , Aged, 80 and over , Blood Coagulation Disorders/pathology , COVID-19/pathology , Endothelial Cells/metabolism , Endothelial Cells/ultrastructure , Endothelium, Vascular/ultrastructure , Female , Humans , Hypoxia/pathology , Lung/ultrastructure , Male , Middle Aged
13.
PLoS One ; 16(9): e0258134, 2021.
Article in English | MEDLINE | ID: covidwho-1448581

ABSTRACT

Pesticides use in Southeast Asia has increased steadily, driven by the growth of large-scale commercial farming, as well as a desire to maximise food production in rural subsistence economies. Given that use of chemical pesticides, such as organophosphates and carbamates, has known potential health impacts, there are concerns about the safety of agricultural workers, and a need for a better evidence base to underpin regulation and worker education. This study, undertaken in 9 districts in Lao PDR, Thailand and Vietnam, will interview agricultural workers to investigate how they use pesticides, their knowledge of risks and self-protective practices, and their self-reported illness symptoms. In each district researchers will recruit and interview 120 participants engaged in vegetable farming, who have recently used pesticides, making a total of 1080 subjects divided equally between the three study countries. Workers' degree of pesticides exposure will be determined from acetyl cholinesterase concentrations in capillary blood samples collected using field test kits, and these data will be analysed together with the interview findings. Country findings will be compared and contrasted, and general patterns noted. Knowledge gained about risky behaviours, self-protective practices and degree of association with serious pesticides exposure will assist policy makers and inform health improvement programmes.


Subject(s)
Acetylcholinesterase/blood , Agricultural Workers' Diseases/blood , Farmers , Health Knowledge, Attitudes, Practice , Occupational Exposure/analysis , Pesticides/analysis , Research Design , Health Status , Humans , Laos , Thailand , Vietnam
14.
Journal of Epidemiology and Community Health ; 75(Suppl 1):A3, 2021.
Article in English | ProQuest Central | ID: covidwho-1394144

ABSTRACT

BackgroundAsymptomatic transmission of SARS-CoV-2 poses a significant burden on managing the spread of COVID-19. Few studies have evaluated the impact of testing for asymptomatic COVID-19 among large populations or whole cities using empirical data. No study to our knowledge has considered if such interventions result in or exacerbate existing socioeconomic inequalities. The aim of our study is to explore social and spatial inequalities in uptake and case-detection of rapid lateral flow SARS-CoV-2 antigen tests (LFTs) offered to people without symptoms of COVID-19 in Liverpool between 6th November 2020 and 31st January 2021.MethodsLinked pseudonymised records for asymptomatic residents in Liverpool (UK) who received a LFT for COVID-19 between 6th November 2020 to 31st January 2021 were accessed using the Combined Intelligence for Population Health Action (CIPHA) data resource. Bayesian Hierarchical Poisson Besag, York, and Mollié models were used to estimate ecological associations for uptake and positivity of testing.Results214 525 residents (43%) received a LFT identifying 5557 individuals as positive cases of COVID-19 (1.3%). Uptake was highest in November when there was military assistance. High uptake was observed again in the week preceding Christmas and was sustained into a national lockdown. Overall uptake and repeat testing were lower among males (e.g. 40% uptake over the whole period), Black Asian and other Minority Ethnic groups (e.g. 27% uptake for ‘Mixed’ ethnicity) and in the most deprived areas (e.g. 32% uptake in most deprived areas). These population groups were also more likely to have received positive tests for COVID-19. Models demonstrated that uptake and repeat testing were lower in areas of higher deprivation, areas located further from test sites and areas containing populations less confident in the using Internet technologies. Positive tests were spatially clustered in deprived areas.ConclusionOur study provides the first substantial evidence on inequalities involved in large-scale asymptomatic rapid testing of populations for SARS-CoV-2. Large-scale voluntary asymptomatic community testing saw social, ethnic, and spatial inequalities in an ‘inverse care’ pattern, but with an added digital exclusion factor. While test uptake was popular, there was a disconnect between the populations accessing testing and those experiencing harms relating to COVID-19. COVID-19 testing and support to isolate need to be more accessible to the vulnerable communities most impacted by the pandemic, including non-digital means of access.

15.
Blood ; 136(Supplement 1):42-43, 2020.
Article in English | PMC | ID: covidwho-1338953

ABSTRACT

IntroductionIntravenous (IV) daratumumab has become a standard in the treatment of MM and AL amyloidosis largely due to its significant clinical benefit. Due to the high risk of infusion-related reactions (IRRs), it is associated with prolonged infusion times. These lengthy administrations can limit clinic capacity, require split dose infusions, increase chair time, decrease patient satisfaction, and create access barriers in the era of COVID-19. Recently, a fixed-dose subcutaneous (SC) formulation of daratumumab was approved for the treatment of MM, and the safety-run in results (N=28 patients) from a phase III, randomized trial in AL amyloidosis using the SC formulation were published. The SC formulation has the potential to mitigate some of the setbacks from IV formulation and help improve efficiency in the era of COVID-19, where most clinics are faced with limiting and spreading out volume due to space constraints and social distancing requirements. We present real world evidence from a large academic center's experience with adoption of SC formulation to help overcome current challenges.MethodsWe prospectively reviewed all patients being treated with IV daratumumab for MM and/or AL amyloidosis at Boston Medical Center Health System (a 500+ bed integrated delivery network) that would be candidates for the SC formulation. A protocol was designed to switch patients that were currently on IV daratumumab as well as patients newly initiating daratumumab to the SC formulation. Patients deemed eligible were switched to the SC formulation under pharmacy benefit (pending insurance authorization by a pharmacy liaison) at their next scheduled infusion visit. Rationale for switching patients to pharmacy benefit was to support home administration during future surge from COVID-19, using our specialty pharmacy travel RN program. Patients that were naïve to daratumumab, started their first dose as a SC injection. Patients were monitored for 30 minutes following the first SC dose and were pre-medicated with oral acetaminophen, dexamethasone, and diphenhydramine. Patient and nursing satisfaction were assessed after switching to SC daratumumab, using internally developed surveys. Using wholesale acquisition cost, cost analysis was performed between the two formulations. Infusion chair time, improvement in clinic efficiency (using our standard infusion time of 90 minutes for IV daratumumab infusions after the 2nd dose), and safety were assessed and compared.ResultsA total of 26 patients were treated with daratumumab for MM and AL amyloidosis from June 1, 2020 to August 1, 2020. 85% (22/26) of patients were administered the SC formulation. Of these 22 patients, 68% of patients were switched from the IV formulation (15/22) and 32% (7/22) were naïve to daratumumab. The majority (14/22) of SC administrations were patients receiving daratumumab monotherapy for relapsed MM. A breakdown of patient regimens and insurance type is seen in table 1. IRRs were reported in 0 patients starting [or transitioning to] SC daratumumab. Injection site reactions were not reported in any patient. One patient had facial and neck swelling 2 days after administration of SC daratumumab (with no other symptoms) but resolved within 24 hours of an additional dose of dexamethasone and did not recur upon re-challenge of SC daratumumab. Severe neutropenia (ANC less than 500) was reported in 9% of patients (2/22), both patients in the group naïve to daratumumab. Febrile neutropenia was not seen. One patient was being treated with concomitant pomalidomide and the second was treated with lenalidomide and had a baseline ANC of 500 prior to initiation of therapy. Adoption of SC daratumumab led to elimination of 133 hours of chair time and nursing time, or 1260 hours annualized for the year. Cost savings with the elimination of nursing time translates to approximately $100,000 to the institution and approximately $230,000 to the payer. The results compiled from patient and nursing satisfaction surveys are being analyzed and will be presented.ConclusionWe report a s ccessful conversion and adoption of SC daratumumab at our ambulatory hematology/oncology clinic. Insurance authorization does not appear to limit the adoption of this therapy in clinic irrespective of diagnosis or regimen used. Furthermore, the reduction in chair time and patient convenience was largely beneficial in light of COVID-19 to minimize patient exposure in clinic.

16.
Lancet Respir Med ; 9(7): 773-785, 2021 07.
Article in English | MEDLINE | ID: covidwho-1337040

ABSTRACT

BACKGROUND: Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital. METHODS: In this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). We included all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and in-hospital mortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantifying potential mediators (level of respiratory support and steroid treatment). The primary outcome was weekly in-hospital mortality at 28 days, defined as the proportion of patients who had died within 28 days of admission of all patients admitted in the observed week, and it was assessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260. FINDINGS: Between March 9, and Aug 2, 2020, we recruited 80 713 patients, of whom 63 972 were eligible and included in the study. Unadjusted weekly in-hospital mortality declined from 32·3% (95% CI 31·8-32·7) in March 9 to April 26, 2020, to 16·4% (15·0-17·8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0·68 [95% CI 0·65-0·71]). The higher proportions of patients with severe disease and comorbidities earlier in the first wave (March and April) than in June and July accounted for 10·2% of this reduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroids accounted for 22·2%, OR 0·95 (0·94-0·95) of the reduction in in-hospital mortality. INTERPRETATION: The reduction in in-hospital mortality in patients with COVID-19 during the first wave in the UK was partly accounted for by changes in the case-mix and illness severity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortality is not explained by these factors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain. FUNDING: National Institute for Health Research and the Medical Research Council.


Subject(s)
COVID-19/mortality , Hospital Mortality , Aged , Aged, 80 and over , COVID-19/epidemiology , Clinical Protocols , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , United Kingdom/epidemiology , World Health Organization
17.
BMJ ; 374: n1637, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1299224

ABSTRACT

OBJECTIVE: To assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres. DESIGN: Observational cohort study. SETTING: Community LFT pilot at covid-19 testing sites in Liverpool, UK. PARTICIPANTS: 5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020. INTERVENTIONS: Participants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites. MAIN OUTCOME MEASURES: Sensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease. RESULTS: Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >106 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>104 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<104 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load. CONCLUSIONS: The Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19/diagnosis , Carrier State/diagnosis , Carrier State/virology , Adult , COVID-19/complications , Cohort Studies , Female , Humans , Male , Pilot Projects , Predictive Value of Tests , ROC Curve , Reverse Transcriptase Polymerase Chain Reaction , United Kingdom
18.
Lancet Reg Health Eur ; 6: 100107, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1225323

ABSTRACT

BACKGROUND: Large-scale asymptomatic testing of communities in Liverpool (UK) for SARS-CoV-2 was used as a public health tool for containing COVID-19. The aim of the study is to explore social and spatial inequalities in uptake and case-detection of rapid lateral flow SARS-CoV-2 antigen tests (LFTs) offered to people without symptoms of COVID-19. METHODS: Linked pseudonymised records for asymptomatic residents in Liverpool who received a LFT for COVID-19 between 6th November 2020 to 31st January 2021 were accessed using the Combined Intelligence for Population Health Action resource. Bayesian Hierarchical Poisson Besag, York, and Mollié models were used to estimate ecological associations for uptake and positivity of testing. FINDINGS: 214 525 residents (43%) received a LFT identifying 5192 individuals as positive cases of COVID-19 (1.3% of tests were positive). Uptake was highest in November when there was military assistance. High uptake was observed again in the week preceding Christmas and was sustained into a national lockdown. Overall uptake were lower among males (e.g. 40% uptake over the whole period), Black Asian and other Minority Ethnic groups (e.g. 27% uptake for 'Mixed' ethnicity) and in the most deprived areas (e.g. 32% uptake in most deprived areas). These population groups were also more likely to have received positive tests for COVID-19. Models demonstrated that uptake and repeat testing were lower in areas of higher deprivation, areas located further from test sites and areas containing populations less confident in the using Internet technologies. Positive tests were spatially clustered in deprived areas. INTERPRETATION: Large-scale voluntary asymptomatic community testing saw social, ethnic, digital and spatial inequalities in uptake. COVID-19 testing and support to isolate need to be more accessible to the vulnerable communities most impacted by the pandemic, including non-digital means of access. FUNDING: Department of Health and Social Care (UK) and Economic and Social Research Council.

19.
Acta Crystallogr C Struct Chem ; 76(Pt 12): 1043-1050, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1040909

ABSTRACT

The first example of molecular docking of the SARS-CoV-2 main protease for COVID-19 [Mpro, Protein Data Bank (PDB) code 7BQY] by a chalcone-based ligand, namely, (E)-1-(2,4-dichlorophenyl)-3-[4-(morpholin-4-yl)phenyl]prop-2-en-1-one, C19H17Cl2NO2, I, is presented. Two-dimensional (2D) LIGPLOT representations calculated for the inhibitor N3, viz. N-{[(5-methylisoxazol-3-yl)carbonyl]alanyl}-L-valyl-N1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide, and 7BQY are included for comparison with our chalcone-based complexes. The binding affinity of our chalcone ligand with 7BQY is -7.0 kcal mol-1, a high value which was attributed to the presence of a hydrogen bond, together with many hydrophobic interactions between the drug and the active amino acid residues of the receptor. Docking studies were also performed, employing rigid and flexible binding modes for the ligand. The superposition of N3 and the chalcone docked into the binding pocket of 7BQY is also presented. The synthesis, single-crystal structure, Hirshfeld surface analysis (HSA) and spectral characterization of heterocyclic chalcone-based compound I, are also presented. The molecules are stacked, with normal π-π interactions, in the crystal.


Subject(s)
Antiviral Agents/metabolism , COVID-19/enzymology , Chalcones/metabolism , Coronavirus 3C Proteases/metabolism , SARS-CoV-2/enzymology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Catalytic Domain , Chalcones/chemical synthesis , Chalcones/chemistry , Coronavirus 3C Proteases/chemistry , Crystallography, X-Ray , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Molecular Docking Simulation , Oligopeptides/metabolism , Protein Binding , Stereoisomerism
20.
Org. Process Res. Dev. ; 6(24): 940-976, 20200619.
Article in English | WHO COVID, ELSEVIER | ID: covidwho-526153

ABSTRACT

The outbreak of the COVID-19 pandemic has spurred an intense global effort to repurpose existing approved drugs for its treatment. In this review, we highlight the development of seven small-molecule drugs that are currently being assessed in clinical trials for the treatment of COVID-19. Three sections are presented for each drug: (1) history, mechanism of action, and status of clinical trials; (2) scalable synthetic routes and final forms; and (3) outlook for supply should clinical trials show treatment efficacy. A brief overview of diagnostic testing and vaccine development is also presented.

SELECTION OF CITATIONS
SEARCH DETAIL