Researchers at the Canadian Food Inspection Agency (CFIA) National Centre for Foreign Animal Disease (NCFAD) in Winnipeg are refining the genomics tools that could help track the source and spread of future outbreaks of COVID-19 in Canada; research that has played a role in identifying what may be Canada's first case of wildlife to human transmission of COVID.
Finding the best way
Since the beginning of the pandemic, CFIA Research Scientist Dr. Oliver Lung has been leading a genomics effort that has so far sequenced and analyzed several hundred genomes of the virus that causes COVID (SARS-CoV-2) from animals.
In doing so, the researchers have compared methods for sequencing the genome of the virus in a range of situations, including difficult sample types and when there is very little viral material to work with.
Bioinformatic analysis to see who's who and what is changing
Senior Bioinformatician Peter Kruczkiewicz and other members of Dr. Lung's team characterize each sample of the virus, comparing its genome against the millions of SARS-CoV-2 genomes that have been sequenced by researchers in Canada and around the world since the pandemic began.
"The SARS-CoV-2 genome is relatively large for a virus, with more than 29,000 nucleotides," says Dr. Lung. "Every isolate can have a large number of mutations throughout the genome, but isolates that are related will share a lot of the same mutations. This allows us to see, for example, whether we're looking at a Delta or an Omicron variant, or if the mutations can affect the performance of diagnostic tests and vaccine efficacy. Whole-genome sequencing is the only method that allows us to compare the genomes in detail to determine how closely related a SARS-CoV-2 isolate is to isolates collected in different places or at different times, and how the virus is continuously evolving."
Pandemic changed priority
Dr. Lung, head of the Genomics Unit at the NCFAD, points out that when he applied for funding through the Government of Canada's Genomics Research and Development Initiative (GRDI), there was no such thing as COVID.
"There's a lot we still don't know about viruses in wildlife, even though a number of diseases such as HIV/AIDS, Ebola and others, including COVID, are thought to have originated from viruses in animals," says Dr. Lung. "We saw this as an important knowledge gap, so we applied for GRDI funding to establish better laboratory and bioinformatics methods for acquiring and characterizing animal virus genomes efficiently and accurately. This is information that could prove useful in identifying the source of future viral infections. Then COVID happened."
Virus moves between humans and animals
"We know that humans can spread COVID to animals, but so far, animals infecting humans has been very rare," says Dr. Lung. "There were cases of farmed mink infecting humans with COVID in Europe and Canada, and hamsters may have passed the virus to humans in Hong Kong."
In December 2021, Dr. Lung and his collaborators identified SARS-CoV-2 in Canadian wildlife for the first time, and what appears to be the first case of wildlife-to-human transmission of COVID in Canada.
Did the virus move from wildlife to humans in Canada?
"Samples were taken from hundreds of white-tailed deer harvested during the 2021 hunting season in Ontario and Quebec," says Dr. Lung. "We found a number of deer were not only infected with SARS-CoV-2, but were infected with very different strains of the virus.
"While the Quebec deer had the Delta variant, the strain in the Ontario deer was very different from almost all other SARS-CoV-2 sequences. Significantly, it was very similar to the sequence from an individual who had been in contact with deer in the same area and around the same time. But we have not seen anything to suggest sustained human-to-human transmission of this strain."
Genomics investment produces significant results
A collaborator in the project, genomic epidemiologist Dr. Finlay Maguire of Dalhousie University, says these discoveries would not have been possible without the techniques developed by the GRDI-funded team at CFIA.
"Because the samples we collected from deer had only a small amount of viral material in them, we could generate only partial sequences of the virus genome using traditional methods," says Dr. Maguire. "With only a partial genome, you don't know whether you can't find the mutation you're looking for because it's not there, or because it's in the part of the genome you weren't able to sequence. By combining approaches, Dr. Lung was able to generate a number of complete genomes, giving us a lot more confidence in our findings."
More research needed
Dr. Maguire says the research has underlined the significance of the knowledge gap Dr. Lung set out to address at the beginning of the project. "These findings show the need for routine surveillance of viral infections in animals," says Dr. Maguire. "Animals play a part in the evolution of a lot of viruses. There are a number of examples of a virus being passed from humans to animals, where the virus mutated before being passed back to humans."