30 Mar 2022

“It was unlike anything we had seen before”: How genomic sequencing can help us to prepare for future variants

Professor Emma Thomson, OBE, is one of the COG-UK researchers leading the sequencing and analysis of SARS-CoV-2 as it circulates in the UK. We spoke to Emma about her response to the Omicron variant when it first emerged in the UK at the end of November 2021, and what her team uncovered about the variant’s ability to infect and its unique biology.

Professor Emma Thomson and her research team lost a lot of sleep after they saw the first sequence of the Omicron spike protein. While the spike proteins are often seen as shapeshifters, this time, the team encountered something that put them on edge. “What we saw with Omicron was that the spike gene had 30 changes in it compared to other new variants, such as Alpha, which had only 8. It was a significant shift and unlike anything we had seen before.”

While Emma was apprehensive about asking her team to work through a second Christmas during the pandemic, they were eager to further explore the meaning of this newly discovered variant and how it might impact vaccine effectiveness. So began their investigation into how much of a threat the new Omicron variant was.

Their studies revealed that the Omicron variant behaves significantly differently compared to previous variants in its ability to bind to antibodies and in the way that it enters cells, characteristics that are likely to influence immune evasion (an ability to hide from the immune system / escape detection by antibodies) and hyper-transmissibility. Through this, the team were able to better understand how effective current vaccines are in stimulating the body’s immune response, to create antibodies to block Omicron from getting inside of our cells, a process known as neutralisation.

“It’s really important that the antibodies we get from vaccination help to limit [or prevent] the virus from getting into our cells, and we were worried that this wouldn’t be as effective with a virus that looked so different to the original variant used to create vaccines.” They felt somewhat reassured that the vaccines wouldn’t be blunted entirely when they saw the results. “We discovered that while neutralisation was much lower in people who’d had two doses of the vaccine, this increased substantially in people who had received their third dose. We could see that the booster campaign that the government had been pushing across the UK was going to have a protective impact.”

Omicron’s entry process into cells is also significantly different to other variants previously studied. “All variants bind to a protein called ACE2 on the cell surface but the spike protein for pre-Omicron variants is also processed by another protein called TMPRSS2 that sit on the surface of cells. Those variants fuse directly with the cell membrane, which allow the variants to enter straight into cells. Omicron is different in that it doesn’t preferentially use TMPRSS2 to get into cells.” Instead, it is encapsulated in a bubble of membrane called an endosome, enters cells and then has to break out of the endosome using other proteins called cathepsins to gain access to the interior of the cell.

While other variants such as Delta infect cells in the lungs and replicate there, Omicron is less likely to infect lung cells, replicating more efficiently in nasal cells. “The fact that you have more of it in in your nose than in your lungs probably means that it’s easier to transmit, and you may also be less likely to get severe pneumonia. So, if you have high levels in your nose, and you release more virus into the air around you, it’s possible that the virus will travel further, and quicker, to susceptible people.”

Emma believes that while we are fortunate Omicron so far appears to be less severe than preceding variants in populations with high rates of vaccination, we cannot be complacent. “We need to have a process that quickly identifies which spike proteins are associated with entry change and use genomics in the future to predict whether or not the virus is likely to be virulent. We cannot just assume that the next virus is going to behave like Omicron, we’ve got to be aware that there is the possibility for future waves to be more dangerous. We have to be prepared.”


Read the full publication and results HERE.

COVID-19 Genomics UK (COG-UK)

The COVID-19 Genomics UK (COG-UK) consortium works in partnership to harness the power of SARS-CoV-2 genomics in the fight against COVID-19.

Led by Professor Sharon Peacock of the University of Cambridge, COG-UK is made up of an innovative collaboration of NHS organisations, the four public health agencies of the UK, the Wellcome Sanger Institute and sixteen academic partners. A full list of collaborators can be found here.

The COVID-19 pandemic, caused by SARS-CoV-2, represents a major threat to health. The COG-UK consortium was formed in March 2020 to deliver SARS-CoV-2 genome sequencing and analysis to inform public health policy and to support the establishment of a national pathogen sequencing service, with sequence data now predominantly generated by the Wellcome Sanger Institute and the Public Health Agencies.

SARS-CoV-2 genome sequencing and analysis plays a key role in the COVID-19 public health response by enabling the identification, tracking and analysis of variants of concern, and by informing the design of vaccines and therapeutics. COG-UK works collaboratively to deliver world-class research on pathogen sequencing and analysis, maximise the value of genomic data by ensuring fair access and data linkage, and provide a training programme to enable equity in global sequencing.