More than a year after it was identified in Wuhan, China, COVID-19 continues its rampage around the globe. The virus that has now killed more than 3 million people, SARS-CoV-2, has changed as it spreads—acquiring mutations that, in some instances, make it a more formidable foe.
Several SARS-CoV-2 variants, which are versions of the virus carrying mutations that distinguish them from the original strain, have been a cause for concern, due to the possibility they may spread more rapidly, leading to more serious infections, or evading the immune responses evoked by vaccines. For example, B.1.1.7, a variant of SARS-CoV-2 first found in the United Kingdom last winter, raised alarm bells due to its high transmissibility—and is now the dominant strain in many countries, including Canada.
In February, the Canadian Institutes of Health Research (CIHR) put out a call for proposals for initiatives that would address the threat of SARS-CoV-2 variants to public health. This led to the establishment of the Coronavirus Variants Rapid Response Network (CoVaRR-Net), an effort to coordinate and consolidate research efforts across the country to rapidly detect, monitor and assess newly emerging variants and provide rapid guidance for policymakers.
“The purpose of the network is to build and strengthen links between all the research efforts that have to do with COVID-19 and to enable funded projects to come to fruition as rapidly as possible,” says Dr. Ioannis Ragoussis, head of Genome Sciences at the ż´Ć¬ĘÓƵ Genome Centre and one of CoVaRR-Net’s principal applicants (pictured above, right).
CoVaRR-Net, which works in collaboration with the Public Health Agency of Canada's National Microbiology Lab and the Canadian COVID-19 Genomics Network (CanCOGeN), is led by Dr. Marc-André Langlois at the University of Ottawa and was granted $9M in funding by the CIHR.
The network is governed by around a dozen scientists, including two from ż´Ć¬ĘÓƵ. “We distribute the funds to research efforts across Canada and facilitate collaborations to avoid the duplication of work,” Ragoussis says. “Canada is very big and it’s not easy to coordinate the research going on within a province, let alone the entire country.”
The work carried out by CoVaRR-Net researchers spans many different disciplines, including immunology, genomics and the humanities, and is comprised of eight scientific pillars. Ragoussis leads the Viral Genomics and Sequencing pillar, which deals with surveilling and screening for variants—this involves analyzing and characterizing samples of the virus from infected individuals as well as ensuring those samples are correctly labelled and quality controlled before being stored in biobanks.
Another pillar, In Silico Modelling and Computational Biology, is led by Dr. Jesse Shapiro, an associate professor in ż´Ć¬ĘÓƵ’s Department of Microbiology and Immunology (pictured above, centre). Researchers involved in this pillar are responsible for mining sequencing data collected from across the country to find patterns—such as where a variant is emerging and whether it is increasing in frequency—and using that information to advise the relevant authorities about the level of risk posed by a given variant.
Over the past year, labs across Canada have built an enormous amount of capacity for sequencing and accumulated a lot of data, according to Shapiro. “The challenge now is to keep doing all of that, but faster,” he says. Speeding up this process will enable public health officials and policymakers to act in a more proactive, rather than reactive, manner when a concerning variant, such as B.1.1.7, appears within the country’s borders.
Another area of research covered by CoVaRR-Net involves investigating the effects of the variants on immune responses, which is crucial for understanding whether variants will be able to evade the effects of vaccines. Ciriaco Piccirillo, BSc’93, PhD’99, a professor in ż´Ć¬ĘÓƵ’s Department of Microbiology and Immunology, (pictured above, left) is overseeing national efforts to understand how variants influence the response of T cells—a type of immune cell that is essential for instructing the production of antibodies, which the body uses to pin down and attack foreign invaders.
Piccirillo and his colleagues are setting up a pipeline that will include experts who will be able to pinpoint which components of the virus a given mutation affects and develop tests that can determine whether T cells can effectively respond to those changes. Once that data are obtained, Piccirillo explains, they will be used to help those involved in developing vaccines.
Currently, a key focus of the network is B.1.617, a variant that has spread rapidly in India, where the pandemic is causing widespread devastation. The variant harbours two mutations that preliminary research suggests increase the virus’s transmissibility and ability to circumvent the immune response. A handful of cases of B.1.617, which has been labelled by authorities such as the World Health Organization as a “variant of interest,” have been documented in Canada. “Before these very few cases take over, we would like to be proactive and understand exactly how this variant is impacting immune responses and vaccine efficacy,” Piccirillo says. “Our job is to make sure that we are capable of influencing public health authorities with real-time information.”
In addition to monitoring variants as they emerge, another concern of the network is to identify the conditions that lead to the development of such variants. By determining whether factors such as the age, health or immune status of an infected individual influence the chances that a problematic mutation will arise or propagate, researchers may be able to prevent them from developing in the first place. CoVaRR-Net is also involved in many other aspects of the pandemic response, such as monitoring the impact of the variants on Indigenous communities and other ethnic minority groups across Canada.
“Our ultimate goal is to come up with concrete nuggets of information that are sufficiently informative to public health officials, to tell them whether a given variant is of true societal interest in the near future,” Piccirillo says. “Time is truly of the essence here.”
Five additional researchers from ż´Ć¬ĘÓƵ and the Research Institute of the ż´Ć¬ĘÓƵ University Health Centre are involved in CoVaRR-Net: Jorg Fritz, Guillaume Bourque, Silvia Vidal, Don Vinh and Fatima Tokhmafshan.