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1.
EClinicalMedicine ; 38: 101021, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34278277

RESUMO

BACKGROUND: Mandatory Day 2 and Day 8 PCR testing and variant sequencing of international arrivals has been recently introduced by the UK Government to mitigate against cross-border transmission of high-risk SARS-CoV-2 variants. METHODS: SARS-CoV-2 testing and sequencing combines TaqPath CE-IVD COVID-19 RT-PCR with Ion AmpliSeq SARS-CoV-2 Next Generation Sequencing Assay. Retrospective analysis of test trending data was performed from initiation of testing on the 11th March through to the 14th April 2021. FINDINGS: During this time interval, 203,065 SARS-CoV-2 PCR tests were performed, with 3,855 samples testing positive, giving a prevalence of 1.9%. In total 1,913 SARS-CoV-2 genomes were sequenced from positive cases with Ct values < 30 and 1,635 (85.5%) sequences passed quality metrics for lineage analysis. A high diversity of 49 different SARS-CoV-2 variants were identified, including the VOCs B.1.1.7 (Kent; 80.6%), B.1.351 (South Africa; 4.2%), B.1.617.2 (India; 1.7%), P.1 (Brazil; 0.4%) and B.1.1.7 with E484K (Bristol; 0.2%). Vaccine effectiveness was age-related and dose-dependent, ranging from 5% in > 60 with a single dose to 83% in <60 with both doses of a vaccine. Viral load was variant dependent with the B.1.617.2 showing a 21 fold increase in viral copy number compared to the other variants. INTERPRETATION: The unexpectedly high prevalence of COVID-19 infection in UK arrivals is associated with a rich diversity of SARS-CoV-2 high risk variants entering the UK including the VOC B.1.617.2. Vaccination does not preclude infection and its effectiveness is significantly age-dependent and impacted by variant type. The rapid high-throughput test and sequence workflow we have adopted is particularly suited to the monitoring of cross border transmission and enables immediate public health interventions. FUNDING: Data analysis conducted in this study was limited to secondary use of information previously collected in the course of normal care.

2.
Viruses ; 10(5)2018 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-29701642

RESUMO

This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).


Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Proteínas não Estruturais Virais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Benzimidazóis/uso terapêutico , Estudos de Coortes , Feminino , Fluorenos/uso terapêutico , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C/epidemiologia , Hepatite C/genética , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Prevalência , RNA Viral/genética , Sofosbuvir , Falha de Tratamento , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapêutico
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