Now a new study, published in the journal Nature Communications, has mapped how the different Sars-CoV-2 variants evolved as they spread in Toronto from 2020 to 2023, revealing insights that could help fight future outbreaks.
“When the variants started arising in late 2020, there was a lot of interest about the dynamics of the variants, to find out how they spread and evolve within the population,” said senior author, Dr. Wrana, a Senior Investigator at the Lunenfeld-Tanenbaum Research Institute (LTRI), part of Sinai Health.
“There was also a notion that variants could be very dangerous and that maybe they could be controlled through public health measures.”
Dr. Wrana along with Dr. Laurence Pelletier, also a Senior Investigator at LTRI, had already adapted a tool called SPAR-Seq to enable rapid detection of Sars-CoV-2 that they then employed for variant tracking.
Before COVID-19, SPAR-Seq had been developed as a screening tool, in collaboration with Dr. Ben Blencowe’s group at the University of Toronto, and its implementation during the pandemic enabled automated screening and sequencing of thousands of COVID-19 samples at once by focusing on specific, functionally relevant regions of the virus. The sites selected by the team incorporated the region essential for binding to the ACE2 receptor as well as the so-called furin cleavage site necessary for viral infection and transmission. The choice of these regions also allowed for targeted tracking of mutations that could influence the virus's ability to spread and cause disease.
Monitoring variant dynamics in real time
Working closely with Dr. Tony Mazzulli, Microbiologist-in-Chief for Sinai Health and University Health Network (UHN), the researchers monitored over 70,000 samples from the Greater Toronto Area from June 2020 to March 2023. Because the samples were collected and tested daily, this allowed an unprecedented window into how the virus was evolving in real time.
Their findings indicated not only the rise and fall of major variants like Alpha, Beta and Omicron, but also the emergence of numerous sub-variants. Interestingly, many mutations detected in these early sub-variants mirrored those found in later dominant strains such as Omicron, suggesting an ongoing, natural exploration of mutation space by the virus.
“We found Omicron-like mutations in the original Wuhan strain in early samples taken in 2020, indicating that the virus is exploring wide evolutionary space. And that suggests, should a pandemic like this happen again, that you could predict potential evolutionary trajectories of a virus and future harmful variants before they arise,” said Wrana. Such advance knowledge could help inform vaccine and treatment design and other public health measures.
Although the researchers detected numerous sub-variants, none were able to replace the main virus variants, all of which were imported into Canada, the study also found.
The SPAR-seq data also revealed complex patterns of viral transmission within the city, characterized by phases of acceleration and deceleration. This wave-like movement suggested that the spread of variants could be influenced by localized social interactions and the structure of community networks. This nuanced understanding challenges simpler models of viral spread and has implications for public health responses.
Finally, thanks to the depth of coverage of SPAR-Seq, the team was able to detect quasi-species—minor variants within an infected individual—providing insights into the virus's evolution during infection. Again, the virus acquired changes that foreshadowed future changes seen in major variants in the population, a sign of extensive evolution within an individual.
“Together, our findings show that the emergence of dangerous variants could be predicted. Through systematic screening of key domains in viruses, coupled with functional studies in the laboratory, it would be possible to identify variants with high risk for human transmission. This could be powerful tool to predict and manage future pandemics,” said Dr. Wrana.
This video summarizes their research:
All hands on deck in the fight against COVID-19
Trainees Dr. Marie-Ming Aynaud in the Pelletier lab and Dr. Khalid Al-Zahrani in the Schramek and Wrana labs, along with bioinformatician Lauren Caldwell in Dr. Wrana’s group, played pivotal roles in the development and application of SPAR-Seq. While Dr. Aynaud was instrumental for the development of SPAR-Seq, Caldwell created the bioinformatics analysis pipeline and Dr. Al-Zahrani helped with data analysis. They had joined the LTRI teams, globally known for their cancer research, to fight one disease, only to rise to the challenge posed by another.
Because the samples had to be processed within a day to provide results to public health agencies to help curb the spread of COVID-19, the Wrana and Mazzulli’s teams were working around the clock. The development of SPAR-Seq greatly enhanced diagnostic insight into variant strains at Sinai Health, where more than 2.7 million samples were processed between March 2020 and March 2023.
Dr. Anne-Claude Gingras, Director of LTRI and Vice President, Research, for Sinai Health, said, “This work exemplifies collaborative research that we value and foster at Sinai Health. Through the joint efforts of Drs. Wrana, Pelletier and Mazzulli’s teams, not only have we delivered crucial, timely data on COVID-19 for public health agencies during the pandemic, but we have also gained insights into how the virus evolves to enhance public health strategies.”
