Genomic tracking of the COVID-19 pandemic in England

The 'story' of the pandemic
The study, published today in Nature, is the most detailed analysis of SARS-CoV-2 genomic surveillance information to date. It describes the scientific 'story' of the pandemic as it unfolded and underlines the importance of high-speed, large-scale genomic surveillance to understand and respond to infectious outbreaks.

In March 2020, just as England was preparing to enter the first of several lockdowns, the COVID-19 Genomics UK consortium was set up to monitor the spread and evolution of SARS-CoV-2 by sequencing the virus's genome.

Since then, the consortium has identified and monitored numerous viral lineages, including Alpha, first identified in Kent in September 2020 and Delta, first identified in India in April 2021. Both of these lineages subsequently changed the course of the pandemic, not only in England but globally.

For this study, researchers analysed SARS-CoV-2 genomic surveillance data from England collected between September 2020 and June 2021. They characterised the growth rates and geographic spread of 71 lineages and reconstructed how newly emerging lineages spread.

The rise and fall of new variants
At the end of 2020, the Alpha lineage (B.1.1.7) spread despite a series of restrictions, including a national lockdown in November and regional restrictions in December. Though these measures slowed the spread of other lineages, Alpha was found to possess a 50 to 60 per cent growth advantage over previous lineages and continued to spread rapidly.

In the system of tiered restrictions operating in December 2020, infection rates were higher in areas with fewer restrictions. Alpha was only brought under control in a third national lockdown between January and March 2021, which was introduced after a peak of 72,088 daily cases on 29 December. This measure simultaneously eliminated most lineages that had been dominant in September and October 2020. When restrictions began to be lifted on 8 March 2021, the daily case rate had fallen to 5,500.

While Alpha was being brought under control, lineages associated with a greater ability to circumvent immunity from vaccination or prior infection continued to appear in the UK at low levels in early 2021. These lineages were characterised by the spike mutation E484K, the most significant of which were the Beta lineage (B.1.351, first identified in South Africa) and Gamma lineage (P.1, first identified in Brazil). But despite repeated introductions of these lineages, they were confined to short-lived local outbreaks.

In March 2021, the first samples of B.1.617, which originated in India, began appearing in sequence data. This was in fact two lineages, Kappa (B.1.617.1) and Delta (B.1.617.2). The mutations in Delta made the virus much more transmissible than previous lineages. While Kappa spread slowly and has since faded away, Delta had spread to all local authorities and accounted for 98 per cent of viral genomes sequenced by 26 June 2021.

A changing virus
"Time has proven how ingenious an idea it was to set up the COVID-19 Genomics UK consortium at the beginning of the pandemic," said Moritz Gerstung, a senior author of the paper from EMBL-EBI and the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "Being able to see lineages side-by-side, mapped to specific locations, has been incredibly informative in terms of understanding how this series of epidemics has unfolded. To see Alpha growing faster in nearly 250 out of 315 local authorities was a clear signal that we were dealing with something very different. At the same time, we've learned that the genetics of SARS-CoV-2 are incredibly complex. Even though we knew all of Delta's mutations, it wasn't immediately clear that it would become the dominant lineage, for example."

Analysis of Delta indicates that its growth rate was about 60 per cent higher than that of Alpha, the greatest growth advantage observed in any other lineage to date. Overall, the researchers estimate that the spread of more transmissible lineages between August 2020 and the early summer of 2021 more than doubled the average growth rate of the virus in England.

"Thanks to genomic surveillance in the UK and internationally, it is clear that we are dealing a virus that has changed considerably since the one that we faced in March 2020," said Meera Chand, COVID-19 incident director at the UK Health Security Agency (UKHSA) and one of the authors of the paper. "We will continue to monitor the SARS-CoV-2 virus to ensure that we can use the most effective vaccines, treatments and public health measures against current and future variants."

As the Alpha and Delta variants happened to strike the UK at early stages, the UK served as a bellwether to the rest of the world.

The value of genomic surveillance
Although it remains impossible to predict what the virus will do next, the COG-UK consortium has advanced the field of genomic surveillance considerably and proven the value of monitoring for infectious agents. Just 18 months after its inception, the programme now provides near real-time epidemiological information to inform the UK's public health response. It is hoped that one day scientists will be able to use this information to predict the emergence of new lineages.

"These genomic surveillance data have given us a totally new way of watching an outbreak unfold, which has taught us a lot about how a new infectious agent spreads and evolves," explained Jeff Barrett, a senior author of the paper and Director of the COVID-19 Genomics Initiative at the Wellcome Sanger Institute, said: My hope is that similar genomic surveillance programmes will be developed across the world, so that we are as well-prepared as we can be to respond to future infectious disease outbreaks – whether they be familiar pathogens or new ones."

Publication:Harald S. Vöhringer, Theo Sanderson, Matthew Sinnott, Nicola De Maio, Thuy Nguyen, Richard Goater, Frank Schwach, Ian Harrison, Joel Hellewell, Cristina Ariani, Sonia Gonçalves, David Jackson, Ian Johnston, Alexander W. Jung, Callum Saint, John Sillitoe, Maria Suciu, Nick Goldman, Jasmina Panovska-Griffiths, The Wellcome Sanger Institute Covid-19 Surveillance Team, The COVID-19 Genomics UK (COG-UK) Consortium, Ewan Birney, Erik Volz, Sebastian Funk, Dominic Kwiatkowski, Meera Chand, Inigo Martincorena, Jeffrey C. Barrett, Moritz Gerstung: Genomic reconstruction of the SARS-CoV-2 epidemic in England

Nature 2021, DOI: https://doi.org/10.1101/2021.05.22.21257633