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Regular blood donor and paramedic Rebecca Clifton.

handout/Handout

Marc-André Langlois, a virologist at the University of Ottawa, is looking for cab drivers. He’s interested in teachers and daycare workers too, as well as health care workers, staff in long term care facilities and cabin crews on commercial flights.

If he can round up 500 such individuals, whose jobs put them at higher than average risk of catching COVID-19, Dr. Langlois hopes to unlock two related and urgent mysteries surrounding the pandemic: To what degree are people who have had COVID-19 immune from reinfection, and for how long?

Those who recover from COVID-19 develop immune agents in their blood called antibodies that are specific to the virus and indicate who has been infected, whether they had symptoms or not. But what has yet to be discovered is the extent to which those antibodies provide protection from the virus.

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Initial studies of antibody response to COVID-19 offer a mixed picture. One report, published in June in the journal Nature Medicine, suggests that the antibodies can disappear after two months for some individuals who had the virus but did not experience symptoms.

This could mean that for a significant proportion of people, immunity to the disease is short-lived. Yet some other research groups have not seen the same effect, and the latest guidelines from the U.S. Centres for Disease Control and Prevention suggest immunity is maintained for at least three months after an initial case of COVID-19. Further complicating matters, experts caution that the behaviour of the immune system is not determined by antibodies alone.

The federally funded project at the University of Ottawa is just one example of how researchers across Canada are mobilizing to address fundamental unknowns about COVID-19. And while the general pattern of COVID-19 infections is similar around the world, data on immunity that is specific to the Canadian population are needed to inform a host of public-health decisions related to disease vulnerability, including how to prioritize the distribution of vaccines.

Dr. Langlois’s plan is to monitor his surveillance group of 500 for a 10-month period using blood and saliva samples to see whether they contract COVID-19 – in which case they will be notified – or discover if they’ve had it already. This will help shed light on what immune factors may contribute to disease resistance.

“If someone was asymptomatic, was their immune system already primed to resist the virus or are there other genetic factors that didn’t allow the virus to cause severe disease?” Dr. Langlois said.

He will also follow a second group of 500 individuals who have already had COVID-19 and recovered from it. That group would be expected to have some immunity to the virus. Dr. Langlois will watch for signs of reinfection in this group and explore whether the severity of an infection has an effect on subsequent immunity once the virus has cleared.

Because the study is designed to track the same set of individuals over time it will complement larger population surveys aimed at understanding broad shifts in immunity as the virus ebbs or surges.

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“It’s really important for us to understand what the level of protection is in Canada, and how that protection might vary,” said Steven Drews, a clinical microbiologist and associate director at Canadian Blood Services in Edmonton.

Dr. Drews is leading the largest such effort, which involves monitoring blood serum from 1,500 anonymized blood donors every month to check for antibodies produced in response to COVID-19 infection. This research differs from Dr. Langlois’s study in that it does not track immunity in specific individuals but instead gathers snapshots of the general population.

Based on those snapshots, researchers have estimated that roughly 1 per cent of Canadians were exposed to the virus last spring, which is about four times the reported case count. But Dr. Drews notes that tracking the prevalence of the disease based on antibodies doesn’t necessarily indicate whether immunity to COVID-19 is now growing or waning in Canada.

“Because you have an antibody [for the coronavirus], it doesn’t mean you’re protected … and because you don’t have an antibody it doesn’t mean you’re not protected,” he said.

To help cut through the uncertainty, the Canadian Blood Services project plans to use new test devised by Anne-Claude Gingras and colleagues at Mount Sinai Hospital in Toronto. Earlier this year, Dr. Gingras developed a system that could screen thousands of blood samples for the presence of COVID-19 antibodies for large-scale surveys.

The new test involves two molecular components that can be synthesized in the laboratory. One of those components is the tip of the spike protein that the virus uses to fasten onto cells. The other is the ACE2 receptor, the part of the cell that the virus attaches to like a key into a keyhole in order to gain entry. When a donor’s blood sample is combined with those two components, the test can determine to what extent antibodies in the sample are effective at keeping the two components apart – the equivalent of blocking an infection.

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“We’re looking to see if antibodies are capable of a specific function, which is to disrupt the interaction between the host and the viral protein,” Dr. Gingras said.

HOW TO DESIGN A COVID-19

IMMUNITY TEST

The immune system generates antibodies in response to COVID-19 infection. Research teams are now devising laboratory tests that can measure how effective someone’s antibodies are at stopping the virus.

COVID-19 VIRION

Antibody

Spike

protein

ACE2

receptor

HOST CELL

The test consists of synthesized ACE2 receptors that are fixed to a surface. When a solution with portions of synthesized spike protein are added the two components quickly join up.

Synthesized

partial spike

proteins

Synthesized

ACE2 receptors

PLATE

The test consists of synthesized ACE2 receptors that are fixed to a surface. When a solution with portions of synthesized spike protein are added the two components quickly join up.

Antibody

PLATE

When a donor’s blood sample is part of the solution, antibodies in the blood may take up some virus proteins before they have a chance to bind with the receptor. The more receptors are left open the more likely it is that the donor’s antibodies will be able to prevent an infection.

MURAT YÜKSELIR AND IVAN SEMENIUK /

THE GLOBE AND MAIL

HOW TO DESIGN A COVID-19 IMMUNITY TEST

The immune system generates antibodies in response to COVID-19 infection. Research teams are now devising laboratory tests that can measure how effective someone’s antibodies are at stopping the virus.

COVID-19 VIRION

Antibody

Spike

protein

ACE2

receptor

HOST CELL

The test consists of synthesized ACE2 receptors that are fixed to a surface. When a solution with portions of synthesized spike protein are added the two components quickly join up.

Synthesized

partial spike

proteins

Synthesized

ACE2 receptors

PLATE

The test consists of synthesized ACE2 receptors that are fixed to a surface. When a solution with portions of synthesized spike protein are added the two components quickly join up.

Antibody

PLATE

When a donor’s blood sample is part of the solution, antibodies in the blood may take up some virus proteins before they have a chance to bind with the receptor. The more receptors are left open the more likely it is that the donor’s antibodies will be able to prevent an infection.

MURAT YÜKSELIR AND IVAN SEMENIUK / THE GLOBE AND MAIL

HOW TO DESIGN A COVID-19 IMMUNITY TEST

The immune system generates antibodies in response to COVID-19 infection. Research teams are now devising laboratory tests that can measure how effective someone’s antibodies are at stopping the virus.

COVID-19 VIRION

Antibody

Spike

protein

ACE2

receptor

HOST CELL

The test consists of synthesized ACE2 receptors that are fixed to a surface. When a solution with portions of synthesized spike protein are added the two components quickly join up.

Synthesized

partial spike

proteins

Synthesized

ACE2 receptors

PLATE

The test consists of synthesized ACE2 receptors that are fixed to a surface. When a solution with portions of synthesized spike protein are added the two components quickly join up.

Antibody

PLATE

When a donor’s blood sample is part of the solution, antibodies in the blood may take up some virus proteins before they have a chance to bind with the receptor. The more receptors are left open the more likely it is that the donor’s antibodies will be able to prevent an infection.

MURAT YÜKSELIR AND IVAN SEMENIUK / THE GLOBE AND MAIL

Because the test does not require the COVID-19 virus to determine whether it produces immunity, it can be performed in research settings that do not have the high-level biosafety designation needed for dealing with a live virus. That means the test can be scaled up more easily to monitor immunity across thousands of individuals.

Meanwhile, in a separate study, Tania Watts, an immunologist at the University of Toronto, and her colleagues are working to better characterize the full spectrum of the body’s immune response to COVID-19.

Working with blood samples from a smaller group of individuals who have recovered from COVID-19, the team is investigating the role of various immune cells that can seek out and kill the virus or that retain a record of it to marshal the body’s defences if the virus returns.

“I’m actually hoping what we’re doing now will be very useful later on, when vaccine trials are under way and we can compare the vaccine-induced immune response,” to what is observed in those whose immune systems have already been triggered by COVID-19, she said.

Jennifer Gommerman, another University of Toronto immunologist, said the more detailed picture of immunity emerging from such studies is likely to show that immunity to COVID-19 in those who have been exposed is more robust than their blood antibodies alone might suggest.

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“This isn’t some kind of weird monster virus that we lose immunity to at the drop of a hat,” Dr. Gommerman said.

In a recent study with Dr. Gingras and other collaborators, Dr. Gommerman compared saliva and blood samples from individuals who were infected with the virus. They found that some types of antibodies are more present in saliva and could therefore be playing an important role in how some individuals respond to the virus at the place where infection starts – the upper respiratory tract.

“That make sense because that’s the first barrier that virus has to get through,” she said.

Dr. Gommerman said that her next step is to better understand what saliva can reveal about asymptomatic cases and whether, in those individuals, the immune response is faster and more effective than in others. To do this, she is working with a study team based at St. Michael’s Hospital in Toronto to test individuals who have been exposed to the virus and identified through contact tracing, which should yield some asymptomatic cases of the disease.

She added that the results will not only provide a clearer sense of what to expect in terms of infection patterns as the virus continues to circulate, but reveal fundamentally new information about how the human immune system works when confronted with a new pathogen.

“The more we can capitalize on this experiment that’s unrolling on our doorstep, the more we can be prepared for the next pandemic,” she said.

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