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LANCET DIGITAL HEALTH ; 4(4), 2022.
Article in English | Web of Science | ID: covidwho-1935260

ABSTRACT

Background Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. Methods We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. Findings Between June 17, 2020, and April 14, 2021, 47 795 (75.2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86.6%] of 12 909 vs 36 415 [72.4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0.79 [95% CI 0.70-0.89], p=0.0001, for 70-79 years;0.52 [0.46-0.58], p<0.0001, for >80 years), independent of patient demographics and illness severity. 84 (54.2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27.5% in the week before June 16, 2020, to 75-80% in January, 2021. Interpretation Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310948

ABSTRACT

Background: Rapid mobilisation from industry and academia following the outbreak of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to the development and availability of SARS-CoV-2 lateral flow immunoassays (LFAs). High quality LFAs are urgently needed at the point of care to add to currently available diagnostic tools. In this study, we provide evaluation data for ten LFAs suitable for use at the point of care. Methods: COVID-19 positive patients (N=45), confirmed by reverse transcription – quantitative polymerase chain reaction (RT-qPCR), were recruited through the International Severe Acute Respiratory and Emerging Infection Consortium - Coronavirus Clinical Characterisation Consortium (ISARIC4C) study. Sera collected from patients with influenza A (N=20), tuberculosis (N=5), individuals with previous flavivirus exposure (N=21), and healthy sera (N=4), collected pre-pandemic, were used as negative controls. Ten LFAs manufactured or distributed by ASBT Holdings Ltd, Cellex, Fortress Diagnostics, Nantong Egens Biotechnology, Mologic, NG Biotech, Nal von Minden and Suzhou Herui BioMed Co. were evaluated. Results: Compared to RT-qPCR, sensitivity of LFAs ranged from 87.0-95.7%. Specificity against pre-pandemic controls ranged between 92.0-100%. Compared to IgG ELISA, sensitivity and specificity ranged between 90.5-100% and 93.2-100%, respectively. Percentage agreement between LFAs and IgG ELISA ranged from 89.6-92.7%. Inter-test agreement between LFAs and IgG ELISA ranged between kappa=0.792-0.854. Conclusions: LFAs may serve as a useful tool for rapid confirmation of ongoing or previous infection in conjunction with clinical suspicion of COVID-19 in patients attending hospital. Impartial validation prior to commercial sale provides users with data that can inform best use settings.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-305637

ABSTRACT

Background : Angiotensin I converting enzyme 2 (ACE2) is a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and differences in its expression may affect susceptibility to infection. Methods : We performed a genome-wide expression quantitative trait loci (eQTL) analysis using hepatitis C virus-infected liver tissue from 190 individuals. Results : We discovered that polymorphism in a type III interferon gene ( IFNL4 ), which eliminates IFN-λ4 production, is associated with a two-fold increase in ACE2 RNA expression. Conversely, among genes negatively correlated with ACE2 expression, IFN-signalling pathways were highly enriched and ACE2 was downregulated after IFN-α treatment. Negative correlation was also found in the gastrointestinal tract where inflammation driven IFN-stimulated genes were negatively correlated with ACE2 expression and in lung tissue from a murine model of SARS-CoV-1 infection suggesting conserved regulation of ACE2 across tissue and species. Conclusions : We conclude that ACE2 is likely a negatively-regulated interferon-stimulated gene (ISG) and carriage of IFNL4 gene alleles which modulates ISGs expression in viral infection may play a role in SARS-CoV-2 pathogenesis with implications for therapeutic interventions.

4.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294613

ABSTRACT

Introduction SARS-CoV-2 has a complex strategy for the transcription of viral subgenomic mRNAs (sgmRNAs), which are targets for nucleic acid diagnostics. Each of these sgRNAs has a unique 5’ sequence, the leader-transcriptional regulatory sequence gene junction (leader-TRS-junction), that can be identified using sequencing. Results High resolution sequencing has been used to investigate the biology of SARS-CoV-2 and the host response in cell culture models and from clinical samples. LeTRS, a bioinformatics tool, was developed to identify leader-TRS-junctions and be used as a proxy to quantify sgmRNAs for understanding virus biology. This was tested on published datasets and clinical samples from patients and longitudinal samples from animal models with COVID-19. Discussion LeTRS identified known leader-TRS-junctions and identified novel species that were common across different species. The data indicated multi-phasic abundance of sgmRNAs in two different animal models, with spikes in sgmRNA abundance reflected in human samples, and therefore has implications for transmission models and nucleic acid-based diagnostics.

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