Large scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management
Authors: Page Andrew J. , Mather Alison E. , Le-Viet Thanh , Meader Emma J. , Alikhan Nabil-Fareed , Kay Gemma L. , de Oliveira Martins Leonardo , Aydin Alp , Baker Dave J. , Trotter Alexander J. , Rudder Steven , Tedim Ana P. , Kolyva Anastasia , Stanley Rachael , Diaz Maria , Potter Will , Stuart Claire , Meadows Lizzie , Bell Andrew , Gutierrez Ana Victoria , Thomson Nicholas M. , Adriaenssens Evelien M. , Swingler Tracey , Gilroy Rachel A. J. , Griffith Luke , Sethi Dheeraj K. , Davidson Rose K. , Kingsley Robert A. , Bedford Luke , Coupland Lindsay J. , Charles Ian G. , Elumogo Ngozi , Wain John , Prakash Reenesh , Webber Mark A. , Smith S. J. Louise , Chand Meera , Dervisevic Samir , O’Grady Justin ,   The COVID-19 Genomics UK (COG-UK) consortium
Published: October 2020

The COVID-19 pandemic has spread rapidly throughout the world. In the UK, the initial peak was in April 2020; in the county of Norfolk (UK) and surrounding areas, which has a stable, low-density population, over 3,200 cases were reported between March and August 2020. As part of the activities of the national COVID-19 Genomics Consortium (COG-UK) we undertook whole genome sequencing of the SARS-CoV-2 genomes present in positive clinical samples from the Norfolk region. These samples were collected by four major hospitals, multiple minor hospitals, care facilities and community organisations within Norfolk and surrounding areas. We combined clinical metadata with the sequencing data from regional SARS-CoV-2 genomes to understand the origins, genetic variation, transmission and expansion (spread) of the virus within the region and provide context nationally. Data were fed back into the national effort for pandemic management, whilst simultaneously being used to assist local outbreak analyses. Overall, 1,565 positive samples (172 per 100,000 population) from 1,376 cases were evaluated; for 140 cases between two and six samples were available providing longitudinal data. This represented 42.6% of all positive samples identified by hospital testing in the region and encompassed those with clinical need, and health and care workers and their families. 1,035 cases had genome sequences of sufficient quality to provide phylogenetic lineages. These genomes belonged to 26 distinct global lineages, indicating that there were multiple separate introductions into the region.

Furthermore, 100 genetically-distinct UK lineages were detected demonstrating local evolution, at a rate of ∼2 SNPs per month, and multiple co-occurring lineages as the pandemic progressed. Our analysis: identified a sublineage associated with 6 care facilities; found no evidence of reinfection in longitudinal samples; ruled out a nosocomial outbreak; identified 16 lineages in key workers which were not in patients indicating infection control measures were effective; found the D614G spike protein mutation which is linked to increased transmissibility dominates the samples and rapidly confirmed relatedness of cases in an outbreak at a food processing facility. The large-scale genome sequencing of SARS-CoV-2-positive samples has provided valuable additional data for public health epidemiology in the Norfolk region, and will continue to help identify and untangle hidden transmission chains as the pandemic evolves.

Major points

In Norfolk and surrounding regions

100 distinct UK lineages were identified.

16 UK lineages found in key workers were not observed in patients or in community care.

172 genomes from SARS-CoV-2 positive samples sequenced per 100,000 population representing 42.6% of all positive cases.

SARS-CoV-2 genomes from 1035 cases sequenced to a high quality.

Only 5 countries, out of 103, have sequenced more SARS-CoV-2 genomes than have been sequenced in Norfolk for this paper.

Samples covered the entire first wave, March to August 2020.

Stable evolutionary rate of 2 SNPs per month.

D614G mutation is the dominant genotype and associated with increased transmission.

No evidence of reinfection in 42 cases with longitudinal samples.

WGS identified a sublineage associated with care facilities.

WGS ruled out nosocomial outbreaks.

Rapid WGS confirmed the relatedness of cases from an outbreak at a food processing facility.