Search

Background: Covid-19 healthcare worker testing, isolation and quarantine policies had to balance risks to patients from the virus and from staff absence. The emergence of the Omicron variant led to dangerous levels of key-worker absence globally. We evaluated whether using two manufacturers' lateral flow tests (LFTs) concurrently improved SARS-CoV-2 Omicron detection significantly and was acceptable to hospital staff. In a nested study, to understand risks of return to work after a 5-day isolation/quarantine period, we examined virus culture 5-7 days after positive test or significant exposure., Methods: Fully-vaccinated Liverpool (UK) University Hospitals staff participated (February-May 2022) in a random-order, open-label trial testing whether dual LFTs improved SARS-CoV-2 detection, and whether dual swabbing was acceptable to users. Participants used nose-throat swab Innova and nose-only swab Orient Gene LFTs in daily randomised order for 10 days. A user-experience questionnaire was administered on exit. Selected participants gave swabs for viral culture on days 5-7 after symptom onset or first positive test. Cultures were considered positive if cytopathic effect was apparent or SARS-CoV-2 N gene sub-genomic RNA was detected., Results: Two hundred and twenty-six individuals reported 1466 pairs of LFT results. Tests disagreed in 127 cases (8.7%). Orient Gene was more likely (78 cf. 49; OR: 2.1, 1.1-4.1; P = 0.03) to be positive. If Innova was swabbed second, it was less likely to agree with a positive Orient Gene result (OR: 2.7, 1.3-5.2; P = 0.005); swabbing first with Innova made no significant difference (OR: 1.1, 0.5-2.3; P = 0.85). Orient Gene positive Innova negative result-pairs became more frequent over time (OR: 1.2, 1.1-1.3; P < 0.001). Of individuals completing the exit questionnaire, 90.7% reported dual swabbing was easy, 57.1% said it was no barrier to their daily routine and 65.6% preferred dual testing. Respondents had more confidence in dual versus single test results. Viral cultures from days 5-7 were positive for 6/31 (19.4%, 7.5%-37.5%) and indeterminate for 11/31 (35.5%, 19.2%-54.6%) LFT-positive participants, indicating they were likely still infectious., Conclusions: Dual brand testing increased LFT detection of SARS-CoV-2 antigen by a small but meaningful margin and was acceptable to hospital workers. Viral cultures demonstrated that policies recommending safe return to work ~ 5 days after Omicron infection/exposure were flawed. Key-workers should be prepared for dynamic self-testing protocols in future pandemics., Trial Registration: https://www.isrctn.com/ISRCTN47058442 (26 January 2022)., Competing Interests: Declarations Ethics approval and consent to participate The study protocol was developed with the UK Covid-19 Testing Initiatives Evaluation Board (TIEB) and approved by UK Health Security Agency (UKHSA) Urgent Studies Ethics Committee. TIEB was part of the UK Covid-19 testing initiatives evaluation programme, which included academics and public health professionals independent of this study. The motivation for the study came from a request by Merseyside Resilience Forum to UKHSA and NHS England to vary Covid-19 testing policies in response to dangerous levels of NHS staff absence in December 2021. TIEB signed off the study protocol on 4th January 2022 and UKHSA Research Support and Governance Office approved the study on 25th January 2022 as NR0308. The sponsor code for this study is UoL001685 and trial registration code IRAS ID 311842; https://www.isrctn.com/ISRCTN47058442. Competing interests All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest and declare: funding from the Department of Health and Social Care, Economic and Social Research Council, and National Institute for Health and Care Research; no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. IB, TF and MGS were members of the UK Covid-19 Testing Initiatives Evaluation Board but did not take part in sessions where this study was adjudicated. The City of Liverpool received a donation from Innova Medical Group towards the foundation of the Pandemic Institute but neither Innova Medical Group or any other commercial entity gave any support to this study or had any participation in it. Lateral Flow Test supply and company interactions was handled independently by the UK Health Security Agency. LT has received consulting fees from MHRA; and from AstraZeneca and Synairgen, paid to the University of Liverpool; speakers’ fees from Eisai Ltd, and support for conference attendance from AstraZeneca., (© 2024. The Author(s).)

Objectives: To understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risks, perceived risks and the feasibility of risk mitigations from experimental mass cultural events before coronavirus disease 2019 (COVID-19) restrictions were lifted., Design: Prospective, population-wide observational study., Setting: Four events (two nightclubs, an outdoor music festival and a business conference) open to Liverpool City Region UK residents, requiring a negative lateral flow test (LFT) within the 36 h before the event, but not requiring social distancing or face-coverings., Participants: A total of 12,256 individuals attending one or more events between 28 April and 2 May 2021., Main Outcome Measures: SARS-CoV-2 infections detected using audience self-swabbed (5-7 days post-event) polymerase chain reaction (PCR) tests, with viral genomic analysis of cases, plus linked National Health Service COVID-19 testing data. Audience experiences were gathered via questionnaires, focus groups and social media. Indoor CO 2 concentrations were monitored., Results: A total of 12 PCR-positive cases (likely 4 index, 8 primary or secondary), 10 from the nightclubs. Two further cases had positive LFTs but no PCR. A total of 11,896 (97.1%) participants with scanned tickets were matched to a negative pre-event LFT: 4972 (40.6%) returned a PCR within a week. CO 2 concentrations showed areas for improving ventilation at the nightclubs. Population infection rates were low, yet with a concurrent outbreak of >50 linked cases around a local swimming pool without equivalent risk mitigations. Audience anxiety was low and enjoyment high., Conclusions: We observed minor SARS-CoV-2 transmission and low perceived risks around events when prevalence was low and risk mitigations prominent. Partnership between audiences, event organisers and public health services, supported by information systems with real-time linked data, can improve health security for mass cultural events., Competing Interests: DeclarationsCompeting Interests: The City of Liverpool received a donation from Innova Medical Group Inc. towards the foundation of the Liverpool Pandemic Institute after the conduct of this study. None of that donation has supported the research reported here or any of the authors’ work to date. WJE was a member of the UK Events Research Programme Science Board. This paper was commisioned by Commissioned by the UK Department for Culture, Media and Sport.

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Faculty of Public Health.)

BackgroundThe PCR quantification cycle (C q ) is a proxy measure of the viral load of a SARS-CoV-2-infected individual.AimTo investigate if C q values vary according to different population characteristics, in particular demographic ones, and within the COVID-19 pandemic context, notably the SARS-CoV-2 type/variant individuals get infected with.MethodsWe considered all positive PCR results from Cheshire and Merseyside, England, between 6 November 2020 and 8 September 2021. C q distributions were inspected with Kernel density estimates. Multivariable quantile regression models assessed associations between people's features and C q .ResultsWe report C q values for 188,821 SARS-CoV-2 positive individuals. Median C q s increased with decreasing age for suspected wild-type virus and Alpha variant infections, but less so, if not, for Delta. For example, compared to 30-39-year-olds (median age group), 5-11-year-olds exhibited 1.8 (95% CI: 1.5 to 2.1), 2.2 (95% CI: 1.8 to 2.6) and 0.8 (95% CI: 0.6 to 0.9) higher median C q s for suspected wild-type, Alpha and Delta positives, respectively, in multivariable analysis. 12-18-year-olds also had higher C q s for wild-type and Alpha positives, however, not for Delta. Overall, in univariable analysis, suspected Delta positives reported 2.8 lower median C q s than wild-type positives (95% CI: 2.7 to 2.8; p < 0.001). Suspected Alpha positives had 1.5 (95% CI: 1.4 to 1.5; p < 0.001) lower median C q s than wild type.ConclusionsWild-type- or Alpha-infected school-aged children (5-11-year-olds) might transmit less than adults (> 18 years old), but have greater mixing exposures. Smaller differences in viral loads with age occurred in suspected Delta infections. Suspected-Alpha- or Delta-infections involved higher viral loads than wild type, suggesting increased transmission risk. COVID-19 control strategies should consider age and dominant variant.

Background: Our study examines if SARS-CoV-2 infections varied 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., Methods: Population cohort study using electronic health records for 2.7 M residents in Cheshire and Merseyside, England (3rd June 2021 to 1st March 2022). Our outcome variable was registered positive test for SARS-CoV-2. Explanatory variables were vaccination status, previous registered positive test and neighbourhood socioeconomic deprivation. Cox regression models were used to analyse associations., Results: Originally higher SARS-CoV-2 rates in the most socioeconomically deprived neighbourhoods changed to being higher in the least deprived neighbourhoods from the 1st September 2021, and were inconsistent during the Omicron wave. Individuals who were fully vaccinated (two doses) were associated with fewer registered positive tests (e.g., individuals engaged in testing between 1st September and 27th November 2021-Hazards Ratio (HR) = 0.48, 95% Confidence Intervals (CIs) = 0.47-0.50. Individuals with a previous registered positive test were also less likely to have a registered positive test (e.g., individuals engaged in testing between 1st September and 27th November 2021-HR = 0.16, 95% CIs = 0.15-0.18. However, the Omicron period saw smaller effect sizes for both vaccination status and previous registered positive test., 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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., Competing Interests: Declaration of interests None exist., (Copyright © 2022. Published by Elsevier B.V.)

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. 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. 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. 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. National Institute for Health Research and the Medical Research Council. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss their experiences at Boston Medical Center (BMC) in Massachusetts in implementing a pharmacist-driven evaluation and prescribing of COVID-19 therapeutics to infected patients. Other topics include BMC's multidisciplinary strategy to enhance coronavirus-related patient care, and the roles of pharmacy leadership, infectious diseases providers and pharmacists, and ambulatory care pharmacists in the system.