RESUMEN
The first confirmed case of COVID-19 in Quebec, Canada, occurred at Verdun Hospital on February 25, 2020. A month later, a localized outbreak was observed at this hospital. We performed tiled amplicon whole genome nanopore sequencing on nasopharyngeal swabs from all SARS-CoV-2 positive samples from 31 March to 17 April 2020 in 2 local hospitals to assess viral diversity (unknown at the time in Quebec) and potential associations with clinical outcomes. We report 264 viral genomes from 242 individuals-both staff and patients-with associated clinical features and outcomes, as well as longitudinal samples and technical replicates. Viral lineage assessment identified multiple subclades in both hospitals, with a predominant subclade in the Verdun outbreak, indicative of hospital-acquired transmission. Dimensionality reduction identified two subclades with mutations of clinical interest, namely in the Spike protein, that evaded supervised lineage assignment methods-including Pangolin and NextClade supervised lineage assignment tools. We also report that certain symptoms (headache, myalgia and sore throat) are significantly associated with favorable patient outcomes. Our findings demonstrate the strength of unsupervised, data-driven analyses whilst suggesting that caution should be used when employing supervised genomic workflows, particularly during the early stages of a pandemic.
Asunto(s)
COVID-19/virología , Infección Hospitalaria/virología , Brotes de Enfermedades , Genoma Viral/genética , SARS-CoV-2/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/mortalidad , Niño , Preescolar , Infección Hospitalaria/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Femenino , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Quebec/epidemiología , SARS-CoV-2/patogenicidad , Análisis de Secuencia de ARN , Resultado del Tratamiento , Adulto JovenRESUMEN
The first confirmed case of COVID-19 in Quebec, Canada, occurred at Verdun Hospital on February 25, 2020. A month later, a localized outbreak was observed at this hospital. We performed tiled amplicon whole genome nanopore sequencing on nasopharyngeal swabs from all SARS-CoV-2 positive samples from 31 March to 17 April 2020 in 2 local hospitals to assess the viral diversity of the outbreak. We report 264 viral genomes from 242 individuals (both staff and patients) with associated clinical features and outcomes, as well as longitudinal samples, technical replicates and the first publicly disseminated SARS-CoV-2 genomes in Quebec. Viral lineage assessment identified multiple subclades in both hospitals, with a predominant subclade in the Verdun outbreak, indicative of hospital-acquired transmission. Dimensionality reduction identified two subclades that evaded supervised lineage assignment methods, including Pangolin, and identified certain symptoms (headache, myalgia and sore throat) that are significantly associated with favorable patient outcomes. We also address certain limitations of standard SARS-CoV-2 bioinformatics procedures, notably when presented with multiple viral haplotypes.
RESUMEN
The purpose of this study was to describe the effect of muscle damage and delayed-onset muscle soreness (DOMS) on the metabolic response during a subsequent period of prolonged concentric exercise (120 min, approximately 61% V(.)O(2max), on a cycle ergometer), with ingestion of 3 g of (13)C-glucose/kg body mass. We hypothesized that the oxidation of plasma and exogenous glucose would be reduced, while the oxidation of glucose arising from muscle glycogen would be increased. Six male subjects were studied during exercise in a control situation and 2 days following downhill running, at a time when plasma creatine kinase (CK) activity was increased, and DOMS was present. Carbohydrate and lipid oxidation were computed from indirect respiratory calorimetry corrected for protein oxidation, while the oxidation of plasma glucose and muscle glycogen were computed from V(.)(13)CO(2) and the ratio of (13)C/(12)C in the plasma glucose. All data were presented as the mean and the standard error of the mean. The oxidation of protein (approximately 6% energy yield, in the control and the experimental trial), lipid (approximately 15 and approximately 18%), and carbohydrate (approximately 79 and approximately 76%), as well as that of plasma glucose (approximately 41 and approximately 46%), glucose from the liver (approximately 12 and approximately 14%), and glucose from muscle glycogen (approximately 38 and approximately 31%) were not significantly different between the control and experimental (DOMS) trials. The response of the plasma glucose, insulin, lactate, and free fatty acid concentrations was not modified by the previous eccentric exercise. These results indicate that the metabolic response to prolonged concentric exercise is not modified by muscle damage and DOMS resulting from a bout of eccentric exercise performed 2 days before.