Episode 31: Large scale sequencing of SARS-CoV-2 genomes from one region

The microbinfie podcast explores large-scale SARS-CoV-2 genome sequencing efforts in Norfolk, UK, highlighting the critical role of genomic epidemiology during the COVID-19 pandemic.

In a recent discussion, we spoke with Justin O'Grady, Andrew Page, and Alison Mather about their work on sequencing 1,500 SARS-CoV-2 genomes from Norfolk, a small region in the UK. Their efforts contributed significantly to genomic epidemiology, providing a near real-time view of the COVID-19 pandemic as it unfolded. Here are some key insights from their findings:

• Genomic Diversity: Researchers identified 100 distinct UK lineages in the Norfolk area.
• Lineage Distribution Among Key Workers: Sixteen UK lineages were found in key workers but were not observed in patients or within community care settings.
• Sequencing Intensity: They sequenced 172 genomes from SARS-CoV-2 positive samples per 100,000 population, representing 42.6% of all positive cases.
• High-Quality Data: A total of 1,035 SARS-CoV-2 genomes were sequenced to a high standard of quality.
• Global Context: Remarkably, only five countries, out of 103, have sequenced more SARS-CoV-2 genomes than Norfolk for this study.
• Temporal Coverage: The samples spanned the entire first wave of the pandemic, from March to August 2020.
• Evolutionary Rate: The study noted a stable evolutionary rate of 2 single nucleotide polymorphisms (SNPs) per month.
• D614G Mutation: The D614G mutation emerged as the dominant genotype, which is associated with increased transmission rates.
• Reinfection Evidence: There was no evidence of reinfection in 42 cases with longitudinal samples.
• Sublineage Identification: Whole genome sequencing (WGS) identified a sublineage associated with care facilities.
• Outbreak Analysis: WGS effectively ruled out nosocomial (hospital-acquired) outbreaks and confirmed the relatedness of cases from an outbreak at a food processing facility.

Key Points

1. COVID-19 Genomic Surveillance

• Sequenced 1,500 SARS-CoV-2 genomes from the Norfolk region
• Identified 100 distinct UK lineages within a small geographical area
• Sequenced 172 genomes per 100,000 population, covering 42.6% of positive cases

2. Genomic Methodology

• Part of COG-UK consortium, funded by UK government and research organizations
• Used ARTIC Network low-cost sequencing protocol
• Sequenced samples from hospitals, key workers, and various testing pillars

3. Scientific Insights

• Observed D614G spike protein mutation becoming dominant
• Discovered multiple small virus introductions rather than single massive outbreak
• Provided near real-time genomic epidemiology during pandemic

Take-Home Messages

• Whole genome sequencing provides highest-resolution understanding of virus evolution
• Genomic data combined with epidemiological information reveals transmission dynamics
• Low-cost, rapid sequencing protocols enable extensive viral surveillance