Health

The team of scientists guarding Canada against COVID variants—’the known unknown’

The Coronavirus Variants Rapid Response Network will serve as Canada’s early warning system for variants that could hurl us back into pandemic misery

The CoVaRR-Net rapid response network was set up to analyze the variants quickly (Photograph by John Kealey)

The CoVaRR-Net rapid response network was set up to analyze the variants quickly (Photograph by John Kealey)

NOTE, Nov. 29, 2021: The print version of this article was published before the Omicron variant was identified in late November by researchers in Botswana, and cases of it were discovered in Canada. The Coronavirus Variants Rapid Response Network (CoVaRR-Net) is going to analyze Omicron, says its head, Dr. Marc-André Langlois, performing tests “to investigate how antibodies and overall immunity in vaccinated Canadians neutralize and protect against Omicron.”

We seem to be living in a perpetual present, withdrawn from our old lives by necessity, coping with the immediate crises and frustrations inherent in a global emergency. If this limbo has a birthdate, it’s March 11, 2020, when the World Health Organization officially labelled the spread of COVID-19 a pandemic. That announcement occurred little more than two months after the WHO was informed that a novel pathogen had appeared in Wuhan, China, described at the time as a new pneumonia.

As of this writing, roughly 250 million people around the world have contracted what we now call COVID-19, with at least five million recorded deaths. In Canada, more than 1.7 million people have had the disease, and more than 28,000 have died.

Hopes that vaccines could put a stop to this pandemic as quickly as it began were dashed in Canada when health-care systems in Western provinces became overwhelmed with last summer’s surge of new cases. Today, with vaccination rates inching up, masks remain in use across the country as newer measures such as vaccine passports help tamp down outbreaks.

RELATED: What to do as we walk into the pandemic’s fifth wave 

Will 2022 finally bring the joy and optimism we’ve been promised? Or is there another threat lurking that will send us spiralling back to the darkest days of the pandemic?

There is guarded hope among the researchers who serve as our scientific sentinels, evaluating threats and figuring out how to mitigate them. But they know enough of the unpredictability of nature to avoid firm predictions. Even if there is a brighter future in sight, they warn, we need to be able to peer around the corner to see what new threat is coming, and quickly figure out how to deal with it.

That’s why, in February 2021, the Canadian Institutes of Health Research (CIHR) announced it would fund an interdisciplinary network of scientists to “enable a rapid and timely research response” focused on emerging variants of concern. The group will help assess the biological threat posed by mutated versions of the virus, and guide public health decisions. CIHR is providing up to $9 million in funding for the first year of research.

MORE: Fully vaccinated people have gotten the Delta COVID variant. Should we be worried? 

At that time, the vaccination effort had just started, and “variant of concern” had only recently entered the public’s pandemic lexicon, as the Alpha variant of the original SARS-CoV-2 virus ripped through Canada’s pandemic defences. Meanwhile, in India, a new variant, Delta, was spreading with deadly speed.

Within weeks, the Coronavirus Variants Rapid Response Network (CoVaRR-Net) was launched, led by Dr. Marc-André Langlois, a molecular virologist at the University of Ottawa. “This is a Canadian network of Canadian researchers addressing Canadian issues,” he says, adding: “It requires a significant amount of expertise to be able to analyze the variants as they emerge, and analyze them quickly.”

Because variants have a multi-pronged impact on people and communities, CoVaRR-Net is a multidisciplinary group whose members include 13 Canada Research Chairs, with areas of research divided into nine so-called “pillars,” including computational biology and modelling; viral genomics and sequencing; and Indigenous engagement, development and research. By autumn, it had begun 15 projects, exploring, among other questions, why the variants are so transmissible and severe, and producing a “pandemic endgame” analysis that includes “developing methods to track mutations and variants via wastewater.”

READ: Canada is slowing down on first doses, but that could be a good thing 

***

“There are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know.”

Donald Rumsfeld was secretary of defense of the United States when he served up these cryptic yet prescient words. It was 2002, and he was addressing whether Iraq had weapons of mass destruction and was giving them to terrorists (for the record, Iraq didn’t, and wasn’t). But the challenge Rumsfeld described could easily apply to the pandemic as it marks its second anniversary in March. For many, the biggest “known known” is the continued threat posed by variants, especially Delta, which Langlois calls the most preoccupying and worrisome of them all.

At the same time, Langlois, a Canada Research Chair in molecular virology and intrinsic immunity, offers a note of reassurance to those concerned that Delta may acquire further mutations that enable it to fend off vaccines. It could undergo changes that make it slightly more resistant, he says, but overall, the vaccines will continue to be effective against Delta. (In late October, Britain labelled a sub-variant of Delta a “variant under investigation” because it was responsible for a growing number of cases, but early analysis indicated no difference from the original Delta in terms of the risk of severe COVID-19.)

READ: COVID vaccines for children are almost here. How well have we protected the kids so far?

Rather, it’s a “known unknown” that keeps Langlois up at night: “The greatest threat will come from a variant that returns to an animal reservoir—infecting your domestic cat, for example, then mutating in your cat in a certain way that the human system will not allow. And then the virus would be transmitted back to humans in this slightly different form.

“This is what we consider the No. 1 threat to the current vaccines,” Langlois adds, because such a change could render all of them ineffective. In October, his network created a new pillar, “host-pathogen interactions,” led by Dr. Angela Rasmussen, an expert in the field who is a virologist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization.

Researcher Dr. Kiran Nakka (Photograph by John Kealey)

Researcher Dr. Kiran Nakka (Photograph by John Kealey)

The virus that causes COVID, says Rasmussen, “is a generalist, and it can infect a lot of different species.” Already, antibodies have been detected in white-tailed deer, as well as some zoo animals. “It’s not lost on me that a lot of the zoo animals that have been infected are big cats,” she adds. “There’s already quite a bit of data suggesting not only that cats can be infected, but that they can transmit it to each other.”

That concerns Rasmussen, because cats—feral, stray and pet—are present in huge numbers all over the world. Moreover, they interact a great deal, both with each other and with humans.

MORE: The roadblock to full pandemic recovery: ‘Pockets’ of unvaccinated Canadians 

There has already been at least one such inter-species interplay in this pandemic. In late 2020, scientists discovered that humans had spread the virus to mink in Denmark; by the time it was transferred back to people, the virus had acquired mutations. Worried that those changes could threaten the effectiveness of vaccines, Denmark culled 15 million farmed mink.

Another key “known unknown” in 2022: the duration of immunity given by the vaccines, and how new variants will affect those who have already been vaccinated. “We don’t yet have a clear understanding of how long the true protection from these vaccines will last, because there are many more components to immunity than antibody levels in blood,” says Langlois.

Blood samples are stored in a biobank for future pandemic research (Photograph by John Kealey)

Blood samples are stored in a biobank for future pandemic research (Photograph by John Kealey)

In particular, they are looking at T cell response. When people get vaccinated, they train T cells in their body to recognize the spike protein of the virus, explains Dr. Jen Gommerman, a professor at the University of Toronto and a Canada Research Chair in tissue-specific immunity who leads CoVaRR-Net’s immunology and vaccine protection pillar.

After antibody levels naturally drop off post-vaccination, those T cells, along with memory B cells, remember and identify the presence of COVID’s telltale spike protein in the event of a breakthrough infection, rallying the body’s defences. Early studies, including one from the La Jolla Institute for Immunology, found long-lasting T cell memory generated by COVID-19 vaccines, which suggests that healthy people under 65 may continue to be protected by vaccines even as their antibody levels wane. But how long that protection lasts isn’t known.

For those wondering why there is still so much Rumsfeldian uncertainty, Gommerman stresses that scientists are gathering knowledge as the pandemic plays out. “We’ve never had a global rollout of a vaccine campaign in a global pandemic when no one on planet Earth had immunity to this virus,” she says. “Obviously, we’re going to have to learn as we go.”

READ: The pandemic is breaking parents

To aid those efforts, the network is creating a “biobank” of blood, saliva and other samples from people who have been vaccinated. If another variant emerges, or even another pandemic-causing virus, then the network’s labs can use those samples to measure immune responses, Gommerman says. The diversity of the biobank, she notes, reflects that of the Canadian population in terms of age, ethnicity, Indigeneity, gender and even socio-economic status: “We need to know who are the most vulnerable people.”

For researchers, including those at the network, a troubling “known known” is the amount of burnout by those in health care and related academic fields during this pandemic, even while the dangers posed by COVID-19 continue. “These are 80- to 100-plus-hour weeks, non-stop,” Langlois notes, adding that there’s “a relatively small number of people who have been extremely involved in the COVID-19 response because of their expertise, their research, their labs; a lot of the same individuals are basically everywhere.” (In addition, he says, the professors on the network are volunteering their time.)

They also know the public’s interest in getting answers to all things pandemic-related, with Rasmussen in particular doing a lot of outreach on social media. In September, when country singer Paul Brandt questioned on Twitter whether he needed to be immunized—a doctor said he didn’t need the vaccine as he’d had COVID-19— it was Rasmussen who quickly responded, “A virologist in Saskatchewan is telling you otherwise. Vaccination has clear benefits for recovered COVID patients. Please get vaccinated.” (Brandt had intended to be vaccinated before getting the disease.)

They ended up having several long conversations, including one Brandt posted on Facebook that was shared thousands of times, as well as interviews on CBC Radio and CTV, in which she explained that researchers don’t know how long such natural immunity lasts or how strong it is in a particular person. “Dr. Rasmussen has convinced me,” Brandt said in one.

READ: Did the pandemic make post-secondary students more resilient? 

***

Each month, Dr. Nazeem Muhajarine, head of the pillar dealing with public health, health systems and social policy impacts, convenes frontline experts from local health regions across the country in a Zoom call. There, he shares a detailed PowerPoint update on the variants, getting input on common concerns and gathering questions that need answers as soon as possible. His branch then produces recommendations on how to deal with vaccine hesitancy, conducting a federal election campaign during a pandemic, having a safe Halloween and so on.

Blood test: As of Nov. 1, only half the world’s population has had one dose of vaccine (Photograph by John Kealey)

Blood test: As of Nov. 1, only half the world’s population has had one dose of vaccine (Photograph by John Kealey)

Muhajarine, a professor of community health and epidemiology at the University of Saskatchewan, thinks the pandemic will be under control around April, with a national case count between 1,000 and 1,500 a day. “At that level we will have capacity to manage it,” he says.

At the same time, he believes we’ll need to look abroad to keep a handle on what’s happening in Canada. “We have to honour the commitments to COVAX [the initiative to ensure equitable access to vaccines around the world], and get vaccines to African and Asian countries,” says Muhajarine. The effort is going slowly: as of Nov. 1, only half the world’s population had had at least one dose; in Africa, the rate was less than nine per cent.

READ: Meet the University of Saskatchewan student behind Canada’s COVID-19 tracker

If there is one unifying message from CoVaRR-Net’s experts, it’s that the vaccination effort holds the key to our collective future—likely the one action that can spare us living in this endlessly grinding present. “I don’t think this pandemic ends until children are vaccinated,” Gommerman says.

“If we vaccinate 90 per cent of the population,” Rasmussen says, “then I think we have the opportunity to have a very good 2022. I don’t know if we’re ever going to be back to ‘normal.’ I don’t know if we ever should be, because ‘normal’ was quite complacent.

“But I think our day-to-day lives can go back to where we don’t think every five seconds, ‘Where’s my mask?’”


This article appears in print in the January 2022 issue of Maclean’s magazine with the headline, “On guard against the known unknown.” Subscribe to the monthly print magazine here.

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