Large-scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management

Abstract

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 3200 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 organizations 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, 1565 positive samples (172 per 100 000 population) from 1376 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. In total, 1035 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 discrete sublineage associated with six 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; and 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.

Keywords: ARTIC; NGS; SARS-CoV-2; genome; genomic epidemiology; sequencing.

Fig. 1.

Total number of positive samples in the region per week, broken down by type. Not all of these were available for sequencing and a single individual may have been sampled multiple times. Staff (key workers) include healthcare workers and essential workers, such as police officers.

Fig. 2.

Number of positive samples sequenced at Quadram Institute Bioscience (grey bars) over time compared with the number of samples collected (red dashed line). Project sample collection only officially began on 8 April 2020 and not all samples taken before this time were available for sequencing. However, archived samples for March were sequenced and are represented in this figure.

Fig. 3.

Age and sex of positive cases in absolute values (a) and scaled as proportions of all positive cases sequenced (b). Data from one person over 100 years of age are not included. NA, not available.

Fig. 4.

The weekly number of co-occurring global lineages, excluding lineages that were only found in a single sample.

Fig. 5.

The proportion of samples represented by each lineage per week, excluding lineages represented by a single sample. Sample collection for sequencing began on 8 April 2020, and no archival samples were available for sequencing for the period 26 March to 7 April 2020. Samples from July and August were primarily repeated sampling of the same case or with only a single individual in a lineage.

Fig. 6.

Phylogenetic tree of the Norfolk genomes sequenced in this study. The phylogenetic tree was estimated as part of the COG-UK phylogenetic pipeline (7 September 2020). The inner circle represents the UK lineages assigned to each sequence, while the outer circle shows their equivalent global lineages. Only high-quality samples are included (837 sequences). The tree is scaled by nucleotide substitutions per site.

Fig. 7.

Weekly numbers of genomes with the wild type genome (D614) or the D614G mutant in the spike protein.