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UK Test and Sequence Strategy Aims to Block Emerging COVID-19 Strains

Genomic sequencing is yielding critical insights into how the SARS-CoV-2 virus mutates, which variants are the most infectious and how it travels from place to place. Yet sequencing is still rare in most countries, and more than a year since the virus made its deadly debut much about it remains a mystery.

Great Britain has emerged as an international leader in  deciphering the coronavirus’s genetic code: as of the end of December, British scientists had sequenced 7.4% of the country’s COVID-19 positive samples vs. the U.S.’s 0.3%.

A new government regulation is accelerating the pace of genomic research into the virus and cementing the U.K.’s leadership position in the field. As of February 15, all international travellers to Great Britain from  “red list” countries are required to quarantine for 10 days and undergo a polymerase chain reaction (PCR) test, the gold standard for coronavirus detection, on days 2 and day 8. If the traveller tests positive, the sample must be sent to a government-approved lab for genomic sequencing. The rule was prompted by fears regarding coronavirus variants that might prove resistant to vaccines. The B.1.1.7  (Kent) variant, which was first identified in the U.K., does not appear to be vaccine resistant.

To find out more about the U.K.’s sequencing work, ThermoFisher spoke with Dr. Marco Loddo, PhD, and Prof. Gareth Williams, MBChB, PhD, co-founders of Oncologica, the first government-approved provider of COVID-19 PCR testing and genomic sequencing laboratory services.

The pair discussed the company’s COVID-19 testing and SARS-CoV-2 sequencing work to control the spread of the coronavirus.

Q: Oncologica, is a precision oncology services laboratory, focusing on molecular profiling of cancer patients to enable targeted therapies. How did you get into the COVID-19 testing space?

Dr. Loddo: It has been an interesting transition for us. We founded our company in 2014 with a focus on  genomic sequencing to identify patients more likely to respond to certain targeted cancer therapies. When the pandemic began, our initial involvement with COVID testing was to offer it to vulnerable, immunocompromised cancer patients. Subsequently, we were invited by the British government to take part in its national testing program. Our  testing has expanded over the past year, and now we’re testing for private companies, educational institutions and others. More recently, we’ve become one of the companies testing international travellers.

The government’s test-and-sequence program is probably the strongest strategy for protecting the borders from new variants of concern.

Q: Has the TaqPath test been your main tool for COVID testing?

Dr. Loddo: We have been using the TaqPath COVID-19 CE-IVD RT-PCR Kit exclusively. TaqPath’s huge advantage is that it’s a multiplex assay — which means that it targets multiple areas of the SARS-CoV-2 genome, enabling it to detect the presence of the virus even when it’s a mutated version. We’ve found that other company’s tests can struggle, particularly if they’re single- or double-target assays, to pick up some of the new variants. With the TaqPath kit, we’re able to identify all the variants. In fact, part of the new government regulations is that single target RT-PCR tests are no longer allowed for international arrivals; labs must now use a multiplex test that targets at least two genes.

Q: For sequencing under the new travel regulations,* you have been validating the Ion AmpliSeq SARS-CoV-2 Research Panel. Why did you choose it for this work?

Dr. Loddo: In genomic sequencing, there are two parameters, “coverage” and “depth,” which determine the accuracy of the sequencing. The coverage we can achieve with AmpliSeq, compared to other sequencing technologies, gives us more accurate data that we can use to more precisely identify new variants, which was very important to us. On a side note, the minimum coverage requirements set by the government are quite low—50%—while Ampliseq covers more than 99% of the SARS-CoV-2 genome, including all serotypes. It’s really important to quickly link information about new variants to the test and trace program. 

Q: Do you anticipate you’ll be testing a lot of samples through the international arrivals program?

Dr. Loddo: Our capacity is 40,000 tests per day. We had consistent volume of between 15,000-17,000 tests per day until lockdown caused a drop in testing. With new requirements, we expect an extremely high volume of samples from international arrivals, so we are ready to fill up our capacity  for this program. Scaling testing will involve infrastructure expansion and automation, which will enable us to process 40,000 tests per day.

Q: What is the current state of knowledge about the coronavirus variants in the U.K.?

Dr. Loddo: As you know, we had the emergence of the B.1.1.7 (Kent) variant which spread very rapidly. It’s now the most prevalent strain in our country. We even picked up the new B.1.1.7 (Kent) cluster with the E484K mutation, a mutation in the spike protein. This is a variant of concern because, particularly when coupled with the 501Y mutation, it is associated with antigenic change and vaccine bypass.

When the B.1.1.7 (Kent) variant was first characterized in 2020, it had around 26 mutations. Now we’re picking up between 31 and 36 mutations, so the virus is continually changing. It’s so important to pick up these small mutations, which can make a big difference in terms of antigenic change. These changes in the antigens, the virus’s surface proteins, are concerning because a vaccine may no longer recognize the antigens once they’ve changed, and it’s that recognition of the antigens that triggers the immune response to fight off the virus.

Testing and sequencing must be a global endeavour. That’s the only way we can protect our communities from variants traveling around the world.

Q: Once large numbers of people are vaccinated against the coronavirus, is there still a role for genomic sequencing?

Prof. Williams: As more people are immunized, the selective pressure driving these emerging variants will increase. Natural selection will determine which strains become prevalent in the population, as mutations that increase the virus’s transmissibility or ability to evade immune response are most likely to persist. That’s why sequencing is needed to track these strains as they emerge. And again, it’s really important to have full sequencing coverage because the mutational clusters are distributed along the whole of the coding sequence.

Q: What does the future hold for testing and genomic sequencing as a pandemic containment strategy?

Dr. Loddo: This pandemic has really put testing and sequencing on the map, highlighting the importance of both. We have learned how the variants can come across borders very rapidly, often undetected with asymptomatic individuals. I think testing and sequencing are definitely going to be a part of protecting ourselves from future pandemics— being able to identify not just the pathogen and its variants but also the individuals most at risk using immune analysis.

A Look Ahead

Over the coming year, NGS will play a critical role in enabling immune repertoire profiling to determine vaccine response, assess vaccine efficacy and guide the development of more effective, targeted vaccines. Already, clinical researchers are using NGS to better understand immune response to vaccines and efforts are underway to create a repository for COVID-19 patients’ immune repertoires to advance global research and vaccine discovery efforts.

The U.K.’s genomic sequencing requirement began March 1, see interview on ThermoFisher Behind the Bench

The TaqPath COVID-19 CE-IVD RT-PCR kit is labeled “For In vitro Diagnostic Use”.

The Ion AmpliSeq SARS-CoV-2 Research Panel is labeled “For Research Use Only. Not for use in diagnostic procedures.”