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Genomics on a mission to detect new SARS-CoV-2 variants

Dr. Catalina Lopez-Correa and Dr. Gary Van Domselaar

Q&A with Dr. Catalina Lopez‑Correa and Dr. Gary Van Domselaar

Dr. Catalina Lopez-Correa and Dr. Gary Van Domselaar

A new variant of the SARS-CoV-2 virus that spreads faster and more easily, is gaining a foothold in Canadaleaving researchers and public health officials asking if it will rapidly overtake the currently circulating strain.

The Canadian COVID-19 Genomics Network (CanCOGeN) is actively supporting the Public Health Agency of Canada by identifying and sequencing high-priority samples of the virus to help understand potential implications for Canada of the SARS-CoV-2 variant (B.1.1.7) first identified in the U.K. in December and other variants of concern in Canada.

We asked Dr. Catalina Lopez-Correa, Executive Director of CanCOGeN and Dr. Gary Van Domselaar, Chief of Bioinformatics at the Public Health Agency of Canada’s National Microbiology Laboratory, and member of the CanCOGeN Coordinating Committee and the VirusSeq Implementation Committee, to talk about the importance of sequencing and the progress Canada is making in rising to the challenges posed by COVID-19 variants.

“We are bringing genomics out of the lab and applying it to solve concrete problems and inform critical public health and policy decisions. It’s taking science to the next level where we can use that sequencing information not just as part of a research project but as a public health initiative.” — Dr. Catalina Lopez-Correa

“There are very few countries that have a large-scale genomic surveillance program for COVID-19. When you consider the scale of our program, we rank among the top in the world.”  — Dr. Gary Van Domselaar

How is CanCOGeN supporting Canada’s public health response to these new variants?

Van Domselaar: One of the biggest supports CanCOGeN has provided is the capacity to perform nationwide, large-scale sequencing of SARS-CoV-2 genomes. This has allowed Canada to generate around 30,000 genomes over the course of the outbreak. That dataset was instrumental in determining whether these variants were already circulating and prevalent in Canada as soon as they were reported—and none were seen in our databases. This provided valuable information that was used to inform Canada’s decisions surrounding border measures.

Lopez-Correa: One of the main objectives of CanCOGeN is to enable Canada to perform genomic surveillance of COVID-19, including the detection and monitoring of existing and newly emergent variants of concern. When the existence of these variants was reported, we were prepared to respond. That was reflected in our ability to rapidly detect them in Canada.

How did CanCOGeN members mobilize in response to these new variants?

Van Domselaar: Within hours of being reported, CanCOGeN had analyzed the sequence data residing in the national database, which was used to inform the Public Health Agency of Canada. We subsequently convened a response team to determine how to detect these new variants, with representation from public health scientists, epidemiologists, modelers, clinicians, and virologists. The team developed a set of national strategies and priorities for identifying these variants and issued a public health alert on Dec. 23, 2020. The strategies were highly effective — within two days we identified the first B.1.1.7 variant of concern in Canada.

Can you describe how virus sequencing helps us identify and understand these new variants?

Lopez-Correa: What distinguishes viral genome sequencing from diagnostics tests is that the test only tells you the presence or absence of the virus in a clinical specimen. It cannot by itself discriminate between different variants that are circulating in Canada.

Van Domselaar: Genome sequencing adds a whole dimension to the detection—by analyzing the pattern of mutations in the whole genome sequence we can confirm absolutely whether a specimen contains a given variant of concern. Sequencing also allows us to investigate the mutations that occur in these variants so we can check to see if they are associated with increased transmissibility, disease severity, vaccine escape (a term used to describe SARS-CoV-2 variants that could potentially be able to evade vaccine-induced immunity), and testing and vaccine efficacy.

Why is a national consortium like CanCOGeN valuable to this response?

Lopez-Correa: The response would not have been possible without CanCOGeN and our partners. Together, we are drawing on the expertise and abilities of the Canadian public health system and of Canada’s top scientists in public health genomics to structure and implement large-scale genome sequencing for genomic surveillance of coronavirus. We are also leveraging on more than 20 years of investments Genome Canada has made in genomics across the country.

The network is all about partnerships and interacting with different groups. I will say, one key group is the provincial labs that are generating the sequencing data and working nonstop. We also work closely with the Genome Centers, they are helping to build COVID-19 research ecosystems in the provinces and engaging with the public. We have also been interacting with the Canadian mathematical modelling community, with scientists that are developing innovative approaches to help us detect faster the new variants of concern. Basically, we are joining forces with all these different networks.

What do we know about the new B.1.1.7 and B.1.351 variants of SARS-CoV-2?

Lopez-Correa: More recently, we have identified the B.1.1.7 variant (first identified in the U.K.) and the B.1.351 variant (first identified in South Africa) from individuals with no travel history, so it appears to have spread into the community, which we expected. Our rapid response appears to have been effective in identifying the presence of these variants in the earliest stages of transmission, so we are in a much better position to enact public health interventions to limit their spread and give us time to prepare for the scenario that they do establish and become prevalent.

Van Domselaar: We know that these variants had not been observed in Canada from 25,000 sequences collected prior to December 2020. Our rapid detection of these variants allowed us to identify many of them as having come from individuals who have recently returned from international travel, which allows us to intervene quickly and prevent them from spreading in the community. We are now collecting more data on these new variants to investigate possible associations with diseases severity, treatment response and vaccine efficacy.

What is CanCOGeN’s current strategy for virus sequencing?

Van Domselaar: There is way more virus circulating in Canada than we have capacity to sequence. Right now, we’re sequencing over 1,000 genomes per week, but we are working to build up capacity in Canada so we can sequence more of the virus and better track and control the spread of these new variants. We are using the sequence data to perform genomic surveillance for existing variants of concern as well as new variants that may arise in Canada that increase disease severity, transmissibility, and vaccine escape. We also use the sequence data to investigate outbreaks, such as superspreading events.

Lopez-Correa: We are now sequencing about five per cent of positive COVID-19 cases, which is ahead of other comparator countries. Another important aspect is that we have put together a sampling strategy to help us prioritize sequencing across Canada. We are also sharing the data at a global level—first in Canada, then globally. We have spent a lot of time and energy building capacity, creating protocols, creating all these elements that are now having a big impact as we respond to these new variants. The vital role this network is playing in helping us address these big challenges is undeniable.

Has the discovery of these new variants shifted the strategy? If so, how?

Van Domselaar: The discovery of these new variants hasn’t so much shifted the strategy as much as shifted the priorities. Although, we have had to develop specific targeted strategies for detection and monitoring of these variants. These priorities have been distributed broadly to the public health community and frontline workers so they can be implemented, and they have been very successful.

How will the work CanCOGeN is doing now help us respond to challenges posed by this pandemic and future public health crises?

Lopez-Correa: CanCOGeN is contributing substantially to developing the scientific and technical capacity required to perform genomic surveillance and response to COVID-19, but it has also contributed enormous fundamental capacity for public health genomics at large. The Canadian public health community intends to leverage this capacity to apply genomic science and technology for the control and prevention of other circulating infectious diseases in Canada. This should yield significant long-term and long-sought-after benefits for the Canadian public health system.

The Canadian COVID-19 Genomics Network (CanCOGeN) is on a mission to respond to COVID-19 by generating accessible and usable data from viral and host genomes to inform public health and policy decisions, and guide treatment and vaccine development. This pan-Canadian consortium is led by Genome Canada, in partnership with six regional Genome Centres, the National Microbiology Lab and provincial public health labs, genome sequencing centres (through CGEn), hospitals, academia and industry across the country.

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