The COVID-19 pandemic rapidly spread throughout the world, with an initial peak in the UK around April 2020. Over 3,000 cases were reported in the Norfolk region of the UK, a low density population area with a stable population, between March and August, 2020. Whole genome sequencing of clinical SARS-CoV-2 samples, from the Eastern Pathology Alliance, was completed as part of the COVID-19 genomics consortium (COG-UK). The aim was to sequence the genome of all positive SARS-CoV-2 samples to gain insights into the genetic variation and spread within the region and provide context nationally. These samples were collected by four major, and multiple minor hospitals, care facilities, and community organisations within Norfolk and surrounding areas. We combined clinical metadata with these regional SARS-CoV-2 genomes to understand the expansion and transmission of the virus within the region. Overall, 1,565 positive samples (172 per 100,000 population) from 1,376 cases were genome sequenced, with 140 cases having 2-6 samples sequenced. This comprised 42.6% of all positive samples identified by hospital testing in the region encompassing those with clinical need, and health and care workers and their families. 1,035 cases had a genome sequence of sufficient quality to provide phylogenetic lineages. These genomes belong to 26 distinct global lineages, indicating that there were multiple separate introductions into the region. Furthermore there were 100 genetically distinct UK lineages detected demonstrating local evolution and multiple co-occurring lineages as the pandemic continued, at a rate of ~2 SNPs per month. There was evidence of distinct care facility related sublineages and lineages linked to small geographical areas - this data was fed back to Public Health England for further investigation. This study shows the value of large scale genome sequencing of SARS-CoV-2 in surveillance and regional outbreak management.
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