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1.
Molecular Genetics and Metabolism ; 132:S258-S259, 2021.
Article in English | EMBASE | ID: covidwho-1735098

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus (SARSCoV- 2) is a novel virus that causes Coronavirus Disease 2019 (COVID- 19). High-throughput sequencing technologies such as whole genome sequencing (WGS) and sequencing of viral genome DNA are being implemented to identify and report on genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. Genome sequencing has been useful for clinical diagnostic purposes, and can reveal other useful information such as disease risk factors that might lead to disease prevention or patient management strategies. UsingWGS and bioinformatics software tools, we describe a novel pipeline for the analysis of medically relevant genetic results and other findings identified in COVID-19 positive individuals, and the generation of a genome report that can effectively communicate these results to patients and their physicians. Study design: Enrollment will include up to 1500 patients with a positive COVID-19 nasopharyngeal swab. Blood samples will be collected at baseline, 1 month, 6 months, and 1 year after diagnosis. Antibody isotype (IgG, IgA, and IgM), titers, and viral neutralization will be analyzed. DNA will be isolated from blood lymphocytes and host genomes will be sequenced. Whole genomes will be assessed using ACMG criteria for the interpretation of pathogenic sequence variation using in-house and third-party software tools, and publicly available disease and control databases. Comprehensive gene panels will be implemented to allow for patients to receive clinically significant findings, including risk factor and carrier status, from multiple categories of potential genetic conditions including blood and immunology, endocrine, metabolic/mitochondrial, musculoskeletal, hearing loss, neurology, cardiology, ophthalmology, renal, skin, and gastrointestinal disorders. Common disease risk will be assessed using polygenic risk scores calculated for 6 diseases (atrial fibrillation, coronary artery disease, type 2 diabetes, prostate cancer, colorectal cancer, breast cancer). Pharmacogenomic gene variants that alter metabolizer phenotype and drug response in individuals will be reported, in addition to patient HLA-type. The genomic predictions fromABO and Rh blood types will be summarized and reported. Largescale continental ancestry estimation will be performed using publicly available reference populations. Finally, using viral genome DNA sequencing, the SARS-CoV-2 viral lineage will be identified and reported. An appointment with the study genetic counsellor will be scheduled to discuss results identified in the genome report and manage appropriate clinical referrals if necessary. Serology results will be reported. Regression models will examine associations between antibody response (titer, antigen target, viral neutralization ability), physiological response (biochemical, hematological and clinical characteristics), patient outcomes, viral lineage and genomic results. Significance: This study will link clinically relevant genomic results, in addition to other biological and serological characteristics, to potential factors that contribute to variability in SARS-CoV-2 outcomes. Results will be shared with family physicians for clinical follow up. This study will establish an efficient workflow using highthroughput genomic sequencing technology coupled with emerging bioinformatics platforms for the generation of comprehensive genome reports to aid in COVID-19 patient management and follow-up.

3.
Canadian Public Policy-Analyse De Politiques ; 46:S127-S144, 2020.
Article in English | Web of Science | ID: covidwho-1080574

ABSTRACT

We construct a new measure of the aggressiveness of COVID-19 policies in 75 Canadian and American cities and estimate the effect of these policies on mobility patterns in each city. Using a new dataset of five municipal COVID-19 policy indicators for each of our 75 cities, combined with 11 provincial/state policy indicators, we estimate a daily measure of the "aggressiveness" of the provincial/state and municipal COVID-19 policy mix in each city. We then estimate the effects of these policies on subsequent mobility behaviour using dynamic time series models. We find strong evidence of policy effects on subsequent mobility behaviour, but few overall differences between Canadian and American cities. We discuss the significance of our findings both for COVID-19 policy research and for other comparative urban policy research in multilevel policy environments. Les auteurs proposent une nouvelle mesure de la vigueur des politiques visant la COVID-19 dans 75 villes canadiennes et americaines et estiment les repercussions de ces politiques sur les profils de mobilite dans chaque ville. l'aide d'un nouveau jeu de donnees sur cinq indicateurs relatifs aux politiques municipales visant la COVID-19 pour chacune des 75 villes, qu'ils associent a 11 indicateurs relatifs aux politiques provinciales ou etatiques, les auteurs elaborent une mesure quotidienne estimative de la << vigueur >> de la combinaison de politiques provinciales ou etatiques et municipales visant la COVID-19 dans chaque ville. Ils estiment ensuite les repercussions de ces politiques sur le comportement de mobilite subsequent au moyen de modeles dynamiques de series chronologiques. Les resultats qu'obtiennent les auteurs corroborent manifestement les repercussions des politiques sur le comportement de mobilite subsequent, mais les differences qu'ils observent entre les villes canadiennes et americaines sont globalement peu nombreuses. Les auteurs traitent de la signification de ces resultats tant pour la recherche sur les politiques visant la COVID-19 que pour la recherche comparative sur d'autres politiques urbaines dans des environnements oU les decisions relatives aux politiques sont prises par plusieurs ordres de gouvernement.

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