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J Infect ; 83(1): 96-103, 2021 07.
Article in English | MEDLINE | ID: covidwho-1198895


OBJECTIVES: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium. METHODS: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations. RESULTS: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated. CONCLUSIONS: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings.

COVID-19 , SARS-CoV-2 , Bayes Theorem , Hospitals , Humans , Molecular Epidemiology , Renal Dialysis/adverse effects
Mol Cell ; 80(6): 1067-1077.e5, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-909354


The Coronaviridae is a family of positive-strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single-stranded RNA genomes in nature, coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped the in vivo RNA-RNA interactome of the full-length SARS-CoV-2 genome and subgenomic mRNAs. We uncovered a network of RNA-RNA interactions spanning tens of thousands of nucleotides. These interactions reveal that the viral genome and subgenomes adopt alternative topologies inside cells and engage in different interactions with host RNAs. Notably, we discovered a long-range RNA-RNA interaction, the FSE-arch, that encircles the programmed ribosomal frameshifting element. The FSE-arch is conserved in the related MERS-CoV and is under purifying selection. Our findings illuminate RNA structure-based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses and will aid future efforts to develop antiviral strategies.

COVID-19/metabolism , Frameshifting, Ribosomal , Genome, Viral/physiology , RNA, Viral/biosynthesis , SARS-CoV-2/physiology , Virus Replication/physiology , Animals , COVID-19/genetics , Chlorocebus aethiops , Humans , Protein Biosynthesis , RNA, Viral/genetics , Transcription, Genetic , Vero Cells