Tackling the Spread of SARS-CoV-2 Variants

Public health groups and leaders around the world are adopting different approaches for viral tracking and monitoring to halt the spread of novel SARS-CoV-2 variants. The UK’s new “Test and Sequence” strategy requires all international travelers from a “red list” of countries to quarantine for 10 days upon entering the UK, and to undergo a PCR test on days two and eight. Any positive samples are then sent to government-approved labs for genomic sequencing. One such lab is Oncologica.

Until recently Oncologica focused on providing precision oncology testing and molecular profiling of tumor samples. Now, its one of the leaders in the fight against COVID-19, having conducted over 800,000 diagnostic tests.

Technology Networks spoke to Marco Loddo, PhD, co-founder and scientific director of Oncologica and Gareth Williams, MBChB, PhD, co-founder and medical director at Oncologica to understand how the lab pivoted to COVID-19 testing, the situation with the emerging novel variants and the importance of sequencing on a global scale.

Anna MacDonald (AM): How do viral variants emerge?

Gareth Williams (GW): Viruses by their nature evolve and mutate to optimize their chances of survival. When the B.1.1.7 variant was first characterized last year it had around 26 mutations. Now we are picking up between 31 and 36 mutations. As vaccines become more prevalent and more people are immunized, the selective pressure driving these emerging variants will increase. 

AM: Why is it so important to track and monitor these mutations?

Marco Loddo (ML): It is critical to detect mutations as any changes in the virus can make a big difference in its transmissibility and pathogenicity. These changes may also make it less likely for existing vaccines to recognize the virus and trigger an immune response to fight it off.

It is also important that the means of sequencing offers full viral coverage, as new mutations may be distributed anywhere across the virus’s genome. Some assays only cover 50 percent of the genome, but to get the whole signature you need full coverage. We chose the Ion Ampliseq SARS-CoV-2 Research Panel for analyzing samples using next-generation sequencing (NGS) because the panel covers more than 99 percent of the SARS-CoV-2 genome, including all serotypes.

AM: Can you tell us more about the UK’s “Test and Sequence” strategy and its aims? 

ML: The U.K. started the “Test and Sequence” strategy to prevent new, potentially vaccine-resistant strains, from spreading upon entering the country. This new program is probably the strongest approach to protect the borders from new variants of concern.

Under the regulations, all international travelers from what the government has deemed to be “red list” countries must quarantine for 10 days after arrival and then undergo a PCR-based test on days two and eight. It is also important to know that single-target PCR is no longer allowed for new arrival testing; the test needs to be multiplex to ensure it can pick up new variants. Finally, if the traveler tests positive the sample must be sent to a government-approved lab for genomic sequencing.

AM: Oncologica has been supporting testing efforts throughout the pandemic, first with COVID-19 testing and more recently SARS-CoV-2 sequencing. What led you to expand your NGS sequencing capabilities from cancer tumor profiling to now also include SARS-CoV-2 and how did you achieve the change?

GW: We founded Oncologica about eight years ago with a focus on precision oncology and pharmacogenomics. Our interest was in applying genomic sequencing to identify patients who are more likely to respond to targeted therapies and immunotherapies.

When the pandemic hit, we first began using the lab for COVID testing so that it would be available for our vulnerable immunocompromised cancer patients. From there, we were invited to take part in the U.K.’s national testing program. We started testing the most vulnerable people in the community, then extended our testing program to include schools, and most recently have started to support businesses, factories, universities and healthcare institutions to cover a large part of the community. Currently, our COVID testing capacity enables us to process around 35,000 samples a day.

Toward the end of last year the government introduced the idea of sequencing all incoming arrivals to prevent the spread of new variants and we started looking into using our NGS experience for SARS-CoV-2 sequencing. We launched our COVID-19 sequencing program on March 1st and expect volume to grow as more people begin traveling throughout the summer months and lockdown restrictions are eased.

AM: The levels of sequencing per case vary significantly between countries. Why is it important to expand sequencing globally? How can this be achieved?

ML: We have learned variants can come across borders very rapidly, often undetected, with asymptomatic individuals. When we talk about the vaccine, we talk about vaccinating the whole world with global programs. Sequencing will have to take the same approach and be a global testing program to effectively detect and trace emerging strains before they become prevalent in the population.

As more people start traveling internationally again, sequencing programs will be needed to prevent new outbreaks with new variants. The U.K.’s program is very important and I hope it will continue, and that other countries will now start to be more engaged with sequencing as well. Every country should have their own test and sequence strategy as that is the only way to protect communities from variants travelling around the world.

AM: Aside from tracking variants, what other roles can sequencing play in the pandemic?

GW: Sequencing is also important in the context of monitoring vaccine efficacy and developing new, effective vaccines. It is going to be important to integrate information such as T-cell repertoire and B-cell repertoire in the development of vaccines and antivirals, and next-generation sequencing is going to be an integral part of that strategy.

In addition, during the pandemic cancer patients have unfortunately suffered from a lack of treatment and visits. As a result, I think we will see an increased incidence of advanced stage disease in cancer patients in the coming months and years. With that, we will probably see an increased demand for cancer genomic testing to try to identify mutations that can be linked to responsive targeted therapies.

AM: How do you think the pandemic has influenced the future use of sequencing programs in public health?

ML: Sequencing is going to be a part of protecting ourselves from future pandemics. It is not just about being able to identify pathogens but also determining the individuals most at risk. Immune characterization is going to be very important and there is a lot more that can be done using sequencing to identify individuals who may be vulnerable.

One thing we can take from this pandemic is that it has really put molecular diagnostic testing on the map. I think that is going to spread across many other disciplines and applications.

Marco Loddo and Gareth Williams were speaking to Anna MacDonald, Science Writer at Technology Networks.