A new effort to routinely sequence the genes of viruses that cause severe respiratory infections, such as flu and RSV, could lead to better treatments and vaccines
10 January 2023
Virus samples from people with severe respiratory infections, such as flu and RSV, in the UK will be routinely tested by DNA sequencing in a project that could lead to better treatments and vaccines, as well as earlier warning of dangerous new outbreaks. The technology will be trialled on stored nose swabs from covid-19 tests starting later this year, before being rolled out more widely next year.
The team behind the project, called the Respiratory Virus and Microbiome Initiative, says it isn’t aware of any similar plan elsewhere in the world, but it hopes that other countries will adopt the same approach. To encourage this, it will be making all methods and data freely available.
“We hope it will be able to be used globally,” says Ewan Harrison at the Wellcome Sanger Institute in Cambridge, UK, who leads the project.
While it has been possible to sequence viral genomes for decades, it was only during the covid-19 pandemic that many countries began to routinely sequence thousands of samples, which revealed how SARS-CoV-2, the virus behind the disease, was evolving faster than expected. Among other things, this genomic surveillance enabled researchers to detect the first omicron variants and correctly predict that they would cause a huge wave of cases around the world.
“For the first time in human history, large-scale genomics has provided governments and policymakers with forewarning of what’s going to happen in an epidemic, and I think that’s a really important and profound change,” says Harrison. “It’s something we think is really important to further build upon.”
Many other viruses, such as RSV, can also cause serious respiratory infections, he says, but our understanding of them is extremely limited. “Other than a small amount of genome sequencing in flu cases, there really isn’t any routine genomic surveillance of these other viruses,” says Harrison.
At present, the tests commonly used to identify viruses causing severe infections reveal only what type they are, such as rhinovirus or adenovirus, says Judith Breuer, a virologist at University College London.
Sequencing the entire genome of a virus reveals much more information, which can be useful in many ways. For starters, it can help to ensure that people get the most effective treatments. Some antibody treatments for covid-19 may be less effective against newer variants, for example, so doctors can give alternative treatments straight away if they know that someone has one of these variants.
It can also lead to better vaccines. Since SARS-CoV-2 sequencing revealed that omicron variants had spread worldwide and become dominant, mRNA booster shots have been updated to include two of these variants, to make the vaccines more effective against them.
Genetic sequencing can also reveal how viruses are spreading and therefore help to contain them. For instance, if you only know that two people in intensive care have rhinovirus infections, you would have no idea if they were infected in the hospital or out in the community, says Breuer. Sequencing can tell us whether they have exactly the same virus, and therefore if hospital infection control measures need improving.
Last but not least, Harrison hopes to spot emerging new diseases early on. The odds of doing this will be much greater if other countries also do routine genomic surveillance.
Sequencing any of a dozen or so different types of viruses that might be present in a sample is technically more difficult than just sequencing one, especially when the aim is to do so using a cheap test that could be used anywhere in the world. This is why Harrison and his team will perfect their approach using stored swabs before starting to test fresh swabs from critically ill patients in collaboration with the UK Health Security Agency. In the long term, the hope is to expand surveillance beyond those who are critically ill and to other kinds of viruses.
For now, the researchers also plan to sequence all the genetic material present in a few of the swab samples. This approach, known as metagenomics, will enable them to identify every kind of virus, bacterium and fungus present, allowing them to study the microbiome of the respiratory tract.
“The methods and technologies that Ewan and the Sanger are developing will be extremely useful,” says Breuer. “This is an amazingly important initiative.”
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