MRC Seminar Series: “Tracking viral mutations to understand SARS-CoV-2 epidemiology and evolution”

Content originally from Medical Research Council

Continuing the series with the first seminar of 2021, Claire Mooney, Strategic Stakeholder Engagement Manager for the Medical Research Council (MRC) and the organiser of the MRC Seminar Series, writes about the January seminar and the importance of understanding the spread of COVID-19 variants to overcome the pandemic.

Image credit: from the presentation slides by Dr James Shepherd, MRC-University of Glasgow Centre for Virus Research

We’ve all experienced typos and the effects that they can have on the message we wanted to convey. Likewise, in December last year, some simple letter substitutions had major implications for the course of the COVID-19 pandemic, when changes were detected in the genetic code of the SARS-CoV-2 virus. The virus variant known as B1.1.7, was first detected by scientists working as part of UKRI-funded COVID-19 Genomics UK Consortium (COG-UK). At the January MRC Seminar Series, COG-UK member Dr James Shepherd, who is based at MRC-University of Glasgow Centre for Virus Research, described how he and his team led by Professor Emma Thompson have used genomic sequencing to detect and monitor the evolution of the SARS-Cov-2 virus in Scotland and how these changes may affect the vaccines that have already been developed.

The SARS-CoV-2 viral genome sequence is made up of four different nucleotides (represented by the letters A, U, G and C) that encode for or “spell out” different amino acids. When combined in a certain way, these amino acids make up proteins that carry out a function for the virus. Every time a virus infects a person, there is a possibility that it will make a mistake in replicating its genome resulting in a change in the sequence of As, Us, Gs and Cs. If this mutation allows the virus to remain active, it will become fixed in the genome sequence thus generating a new variant of the virus. Some mutations make “silent” changes in the nucleotide sequence which don’t result in changes to the protein or how the virus behaves, while others make changes in both, resulting in different viral behaviour.

In order to monitor these changes, after testing in a Lighthouse lab or NHS diagnostics lab to confirm if a suspected COVID-19 sample is positive or negative, some positive test samples are sent to a COG-UK site. Here, scientists generate the viral genome sequence from the patient sample and different virus variants that are detected can be grouped into lineages based on how similar their genome sequences are. Together with viral genomic data from other countries, these lineages create an evolutionary history known as a phylogeny (similar to a family tree), an example of which is illustrated in the cover image above.

In combination with epidemiological data such as travel histories and clinical records, this information on virus evolution allowed James and his team to determine how SARS-CoV-2 entered and/or re-entered Scotland at different points during the pandemic. By comparing the viral genomes detected in COVID-19 patients in Scotland in March (1314) to viral genomes from other UK and international patients (approx. 18,000), they determined that the virus first entered Scotland through at least 283 travel-related introductions in February and March. Additionally, during a surge of cases in Aberdeen in August, new viral lineages were detected, and it was again deduced that these new lineages were related to travel.

As well as providing information on the origin of new virus variants, knowledge of changes in viral genomes are essential in order to study the effects that mutations will have on countermeasures, such as vaccines. To this end, James’s team and their collaborators conducted experiments to assess how a mutation in the virus spike protein sequence, discovered in the Scottish population and later in England, Wales and Ireland, affected the ability of antibodies to bind to it. Their results indicated that the mutation in question reduced the likelihood of neutralising antibodies to bind to the spike protein, but it did not affect the severity or the spread of the disease. Other work like this is ongoing to see how the B1.1.7 variant, which is prevalent in the UK, may impact the effectiveness of vaccines and treatments.

One thing that struck me during James’s talk was a graph that he presented showing that most of the virus variants detected in Scotland in March had died out during the lockdown in March-June. Having been craving brightness and colour during this most dull and dreary of all the lockdowns (for me at least), it was paradoxically uplifting to see the colourful lines representing different viral variants disappear from the graph. It served as a helpful reminder of how effective lockdowns can be in reducing the number of COVID-19 cases and thus the chances of anymore viral genomic “typos” that could threaten the advances that we’ve made so far.

Click to watch the full video of Dr Shepherd’s seminar.

Click to watch any of the other seminars in the MRC Seminar Series.