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1.
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.

2.
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
3.
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.

4.
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
5.
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
6.
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
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