In this presentation to the National Advisory Committee on Immunization (NACI) in March 2023, Dr. Sarah Otto summarized recent CAMEO work highlighting how SARS-CoV-2 variants have been evolving in Canada. While BQ.* variant lineages dominated in early 2023, the XBB.1.5 variant has been rising rapidly in frequency and now comprises the majority of COVID-19 cases.

XBB.1.5 is a member of the XBB* family of lineages that arose by recombination from two separate BA.2 lineages (“X” in the start of a lineage name refers to a recombined lineage). Lab studies have shown that the family of BQ.* and XBB* lineages are more immune evasive, but the fast spread of XBB.1.5 is thought to be due to its greater ability to bind to our cells’ ACE2 receptors, leading to higher transmissibility.

At present, Canada-wide immunity is high, so these variants no longer lead to big waves, but they do lead to wavelets and, more importantly, to long term rises in the “sea-level” of COVID-19 cases.  Dr. Otto explores models to show how variants are expected to influence future case numbers and how measures that we take can counteract the rising sea-level of COVID-19 (e.g., through vaccinations, improved ventilation, and masking).

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1. Mathematical and Phylogenetic Approaches to Characterize Variants

We are continuously analyzing SARS-CoV-2 genomic sequence data to identify and characterize the epidemiology of new and existing variants. These activities allow us to predict the variants’ rate of spread and their potential impact on health care systems across the country. We communicate this information across CoVaRR-Net pillars and to PHAC to assist in public health decision-making.

2. Duotang

Duotang is a continually updated web-based notebook that contains genomic epidemiology and mathematical modelling analyses. Its purpose is to explore SARS-CoV-2 evolution in Canada with the aim of spurring further research discussion across pillars, supporting discussions with public health authorities, and sharing with the science communication team for eventual public dissemination. The data for Duotang is compiled from the Canadian VirusSeq Data Portal and DNAStack’s Viral AI.

3. Data Sharing

CAMEO is committed to working with the Canadian VirusSeq Data Portal to ensure that Canadian SARS-CoV-2 genome sequences generated by the Canadian Public Health Laboratory Network (CPHLN) and regional health authorities are publicly available without restriction to encourage data re-use for scientific discovery and innovation. We will work with the VirusSeq Data Portal to explore more flexible and comprehensive ways of sharing contextual data in a trusted environment. This will be done by building on the Canadian COVID Genomics Network (CanCOGeN) and CHARGES (Canadian public Health Alliance for Research in Genomic Epidemiology and Surveillance – a CPHLN-led consortium to implement genomic based infectious disease surveillance) efforts to standardize and harmonize contextual information critical for genomics analysis. Our collaboration is focused on ensuring the Data Portal is as user-friendly as possible, while working to add features that are useful to researchers seeking to analyze the data in the Portal. We are also working towards supporting the analyses and visualization of wastewater data from across the country and national priority pathogens.

4. COVID-MVP

COVID-MVP is an interactive heatmap-based visualization tool for SARS-CoV-2.

It tracks the prevalence of SARS-CoV-2 mutations, offering annotations of the functional impact of these mutations in variants of concern (VOCs), variants of interest (VOIs), and user-defined subpopulations in near-real time.

COVID-MVP visualization is powered through an independent, scalable and reproducible genomics workflow using functional annotations manually curated in Pokay.

Pokay is also maintained by our team and is regularly updated by curating new functions from the literature.

5. SARS-CoV-2 Evolution in Animal Reservoirs

We are in the process of analyzing about 2000 SARS-CoV-2 genome sequences of animal origin and inferring their phylogenetic relationships with roughly 2000 matched human sequences. The number of animal-to-human transmission events that have happened during the pandemic will then be estimated, and a genome-wide association study will be conducted to identify any animal-associated mutations. We will then develop methods to track these mutations in wastewater.

6. Environmental Monitoring and Sequencing

In collaboration with the CUBE project and the CoVaRR-Net Wastewater Surveillance Research Group (WWSRG), we are working to develop, benchmark and apply methods to track SARS-CoV-2 mutations and variants in the built environment and in wastewater. These data streams are increasingly important in contexts with limited clinical sampling, and now is the time to validate and compare them to clinical sequence data while it is still available. Working with environmental mixtures of viruses, often at low biomass, poses computational challenges which we are working to address, and modelling how these data types track with cases and hospitalizations is also an active area of research.