analysis | Rapid genome sequencing could save lives after coronavirus

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The term “global beating” is used a lot in the UK, most often used by Prime Minister Boris Johnson. In many cases, it is a selfish exaggeration. However, this is not the case when distributing viral genomes during a pandemic.

A virus’ genome, made up of “letters” of nucleotide bases, is essentially an instruction manual. The UK’s ability to rapidly sequence SARS-CoV-2 samples has allowed the UK to see how quickly the virus is spreading, identify new strains and measure the impact of public health measures.

In fact, to sum up the hopes given the nickname “Global Britain”, where innovation, collaboration and global support thrive, the Covid-19 Genomics UK program, known as COG-UK, checks every box. A collaborative program that includes the National Health Service, four public health agencies, 16 academic partners, and the Wellcome Sanger Institute provides useful examples of how to break down bureaucratic barriers and orchestrate public health decision-making.

COG-UK would not have been possible without the leadership of Sharon Peacock, a microbiologist at the University of Cambridge. Peacock initially had to address her doubts about the usefulness of bulk sequencing. But she has a lot of experience overcoming obstacles.

Therese Raphael and Sam Fazeli spoke to Peacock about how to monitor the development of the current virus, how to leverage Britain’s greatly improved sequencing capabilities for other causes, and the formula for success. The script has been edited for length and clarity.

Therese Raphael: How would you describe the impact of building a near real-time genomic sequencing infrastructure in the UK and globally?

Sharon Peacock: When the pandemic started, we knew how to do sequencing. However, like many countries, we did not have the extensive national network capabilities needed to sequence the SARS-CoV-2 virus.

The question on day one was, can we do sequencing fast enough to influence policies and decisions? In the UK, since early March 2020, sequencing has provided information on mutations that cycle. This was key because I started to strategically order them. Not only do we do sequencing on random samples, we can see them circulating, but we also do sequencing on samples from people who have traveled to see what’s going into the country and see if there’s an outbreak. It has to do with new variants or possible super-spreader events.

With the introduction of vaccines, we sequenced samples from people who had failed the vaccine. We were able to discover new variants and classify whether people have (imaginary) variant A or variant B. This allows the UK to determine the mutation and its degree of contagiousness, the degree of immune evasion and the mortality rate.

Of course, now others have contributed greatly. Denmark and Israel and elsewhere. Global access to all sequencing methods, analysis tools, and sequence data from COG-UK was available. At one point during the pandemic, we sequenced 50% of the global total of SARS-CoV-2. Pathogen sequencing is important to see what SARS-Cov-2 will do next, but that is no longer true as more people are contributing to the genome.

Sam Fazeli: Isn’t it 50% anymore? Anyone still sequencing at a high level?

SP: Our sequencing data no longer accounts for 50% of the total. Because it was probably early in the pandemic when we were sequencing in bulk and ahead of the curve. According to WHO’s latest strategic report, two-thirds of member countries can now be sequenced. So I see it as a good thing that our percentage of the global total is lower because it means other people are sequencing and contributing.

I don’t see it as a competitive term, as small amounts of sequencing performed strategically in certain countries where sequence data has not previously been available can be very valuable. That’s why COG-UK developed the COG-Train.

TR: Is there an ideal number of cases you would like to sequence for a robust sequencing program?

SP: As far as I can see, there is no perfect sweet spot. It depends on the order. Doing a combination of targeted and unbiased sequencing will tell you what’s going on. We covered 10% of the positive cases we thought were realistic and feasible. It went up to 50% or more when the number of cases was very small.

Sequencing is required to detect changes in the virus. And it takes a significant number of people to participate. 10% was actually very helpful to us in terms of the answers we got. Now that we are using a side-flow device that cannot be sequenced, it is not realistic to obtain very high ratios. Between 5% and 10% seems like a reasonable estimate of what you should cover. And the sequencing function is on standby if needed. Remember, unlike diagnostic tests like diabetes for example, you don’t need to know information about your patient’s treatment.

SF: If vaccines don’t prevent infection, as we’ve seen, what’s the value of ongoing genomic testing? In any case, you will be tested as soon as you arrive at the hospital.

SP: What we’ve learned from the pandemic is that the future isn’t easy to predict. We have known for some time that vaccination does not prevent infection. We cannot, in fact, rule out the possibility that other mutations with different biological properties will appear at some point. Of particular concern is the case of some kind of evolutionary lottery, causing more severe disease than previous strains.

For example, as in a report from South Africa with BA.4 and BA.5, kinetic signals that gain or increase in sequencing are first detected and then investigated. So, is there a role for sequencing in the future? totally.

TR: What role do you see in wastewater monitoring going forward?

SP: Wastewater sequencing has been really useful for detecting variants that occur or circulate at different levels of populations. We believe that the future of wastewater sequencing will be practically usable at population level or community size, and at many scales such as schools or hospitals.

Of course, if there is a single instance of a new strain, it will not be very easy to detect as the scale of the waste will have the effect of having to pull the needle from the haystack. However, we believe that wastewater sequencing can be very powerful, especially in areas where there is no sequencing capability at all. For example, in low- and middle-income countries where you don’t know what’s circulating.

TR: Covid has spurred a huge leap in awareness for genomic sequencing. What other applications should we look forward to from a public health perspective?

SP: I think the next pioneer would be adding genomic sequencing to human genome data. We’ve done a lot of sequencing the human genome in the UK, which supports a lot of work on how genetics might make you more susceptible to serious diseases. What we’re going to do now is integrate it with the viral data.

Another region is gearing up for sequencing for the next potential pandemic. Sequencing also plays a role in antimicrobial resistance. The precise application of AMR, which is currently hotly debated.

Whether sequencing should be used in hospitals for infection prevention and control will be a big and important question. Combining epidemiologic data with sequence data from MRSA, for example, gives a much clearer picture of the onset of the disease compared to shoe-leather epidemiology through sequence data.

SF: What are you trying to learn from a patient’s viral mutation sequence when you’re trying to link it with the patient’s genes?

SP: An important outcome is knowing whether a patient has worsening of their infection status compared to others. That’s because you’ll be warned ahead of time and potentially treated in a different way.

For example, a person may already know that condition X does not perform well because of certain risk factors. But the question is, what additional gains in terms of predictive analytics when bringing the pathogen genome along with the host genome? [of an individual who tests positive for SARS-CoV-2]And we are starting to do that now.

TR: I want to ask you about your amazing personal story. I was not given the opportunity to go to college or take science classes from high school. I left school at the age of 16, became a dental nurse in the store, got my nursing degree, studied medicine, and faced night school and various rejections. Obviously you’re compressing a lot. You had the tenacity to persevere. I wonder what will happen before more Sharon Peacocks appear in the UK.

SP: Wouldn’t it be great if there was only one answer to that question! None. I believe there is no turning back in any way we can provide opportunities and education to children and early on. My parents didn’t go to college. We didn’t know anyone in college and nobody in our school went to college. We all left at 16:00 to find work.

If you do not have such an academic environment at home, you should bring it from school. So it’s really important to give the impression to young people that they can really aspire to what they want to do and don’t turn down answers. Perhaps we are better now than we were before. However, talents and abilities come in very different shapes and sizes and begin to mature at different times in life.

I am currently an academic at a university with a particular focus on access to higher education. I initially went to night school for further education, but the door that really changed my life was going to college.

TR: Are you saying we need a more culture that allows for failure and encourages young people to take risks?

SP: Everyone who succeeds has failed many times. Every time you fail, you learn and do something else. So I think we should allow people to fail. And when you look at your CV, it’s very interesting because you’re not talking about failure, you’re only talking about success. I think it’s very important to encourage a culture where people can talk about their failures and what they’ve learned.

More from Bloomberg comments:

• Is increased hepatitis cases in children related to Covid?: Therese Rafael

• Are you running out of milk? Blaming Bad Policies and Bureaucracy: Editors

• Be careful with whatever you want. Economy: Welcome to Conor Sen.

This column does not necessarily reflect the views of the editorial board or Bloomberg LP or its owners.

Therese Raphael is a columnist for Bloomberg Opinion covering healthcare and UK politics. Previously, she was editor of the editorial pages of the Wall Street Journal Europe.

Sam Fazeli is a Senior Pharmaceutical Analyst at Bloomberg Intelligence and Research Director at EMEA.

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