Dr. Evans explains the basics of Canada’s serological testing initiative to help manage COVID-19

What is a serological test?

A serological test is a blood test. This test detects the presence of virus-specific antibodies in blood samples so that previous exposure to the COVID-19 virus can be detected.

Why is the COVID-19 Immunity Task Force being created?

Two reasons. First, there is not enough information on how many Canadians have been infected with the novel coronavirus SARS-CoV-2 but were not tested for it because they had mild or even no symptoms of COVID-19. And second, we do not understand enough about how our immune systems are fighting off the virus.

Why does that information matter?

You can think of it as useful for policy decisions and individual decisions.

At a policy level, we need to understand how many people have been exposed to the virus and might be expected to have some level of immunity to it. We know that number is a lot higher than the number of people with obvious symptoms who were tested and confirmed to have COVID-19 disease. If that number is high, it gives us more latitude to start easing off some of the physical distancing measures that have heavily constrained our social lives and our economy.

At an individual level, we all have an interest in knowing whether we are sufficiently immune to the novel coronavirus SARS-CoV-2 that is unlikely to make us seriously ill if we are exposed to it. And that is particularly important for those in key public-facing jobs, such as healthcare workers, police officers, fire-fighters, and other emergency workers. But it also goes for so many others — such as teachers, because children and youth can be infected with the virus but generally show very few symptoms.

So, is the COVID-19 Immunity Task Force going to test every Canadian?

No, and it is important in that regard to understand the Task Force’s role. There is momentum building across Canada for immunity testing, with various provinces, institutions, and research groups headed in that direction. They will be doing the testing and information gathering. The Task Force is here to support, scale-up, accelerate, and harmonize those efforts so that we can learn as much as possible, as efficiently as possible.

As to testing every Canadian, that may become feasible if COVID-19 immunity testing is incorporated into the various Medicare plans from coast to coast. But there’s a lot more knowledge to be gained before it makes sense to test every Canadian. We are currently in a scanning and sampling phase: taking a first, careful look at the immunity status of different groups of Canadians in different regions, and doing the scientific research to put test results in context and, if necessary, put new tests in the field.

How do you test for immunity to novel coronavirus SARS-CoV-2?

On one level, it’s simple. We can conduct fast screening tests, using a drop of blood, on very large numbers of people to assess whether or not they have measurable levels of antibodies to the novel coronavirus SARS-CoV-2. These test results may give us a rough overall estimate of who has been exposed to the virus and may have built some innate defenses against re-infection leading to onward transmission of COVID-19. But more information is needed to help us navigate our way out of the current social restrictions.

How does that differ from most of the ongoing testing to diagnose COVID-19?

Tests for active COVID-19 focus on identifying the presence of the SARS-CoV-2, the novel coronavirus. The virus can be identified in swabs of the nose and/or throat, or in stool samples, but does not often appear in the bloodstream. SARS-CoV-2 is a single-stranded RNA virus. The definitive test involves looking for a match between RNA in the test sample and the known RNA structure of the virus. This is time-consuming, but faster methods are now coming into use.

In contrast, the immunity tests to date focus on measuring the presence in the blood of antibodies to the novel coronavirus SARS-CoV-2 produced by someone who is infected. A person who is infected may or may not have full-blown COVID-19 symptoms. A huge advantage of measuring antibodies is that this test can identify people who showed very mild or even no symptoms but were never tested. Antibody testing can also give us a look backwards – extending many weeks if not months – at people who had enough exposure to mount an immune response to the virus, but would not be positive if tested for active infection now.

Both tests can produce negative results early in the infection, before the virus is being actively shed and appearing in the nose and throat of a patient, and before the body’s immune system mounts an immune response. But relying on antibody tests for diagnosis of active disease is dangerous, because it usually takes several days for a strong antibody response to occur. Most patients have a measurable antibody response within a week or so, but that is not always the case.

Beyond simple screening, what other information do you need for policy?

First, we need to know if different regions or groups vary. Is there more background immunity in big cities that have dense social networks than in, say, rural and remote communities? We have had many terrible outbreaks in nursing homes and long-term care facilities. How many of the residents and staff show signs of immunity now?

More generally, older persons and persons of all ages with chronic illnesses appear to be more vulnerable to develop severe COVID-19 illness after exposure to novel coronavirus SARS-CoV-2. What proportions of those groups show immunity? Similar questions can be asked about Indigenous communities, as well as children and youth when determining when and how to restart educational programming. Getting reliable first estimates of background immunity in different groups will help us navigate the next phase of this epidemic.

Is this a standard approach to formulating policy in an epidemic?

No. In serious chronic viral diseases, such as Hepatitis C or HIV, the virus itself can be measured in the blood, and large-scale studies may be undertaken to establish patterns of infection. In other cases, such as during flu epidemics, the offending virus is generally not detectable in the blood. When we measure antibodies to the flu virus on a wide scale, we are doing so to guide vaccination strategies rather than make policy decisions about containment measures.

COVID-19, however, has become a massive global challenge which is leading many countries to explore whether and how assessments of background immunity can be used to toggle measures such as mass physical distancing. These large surveys of population immunity may also help to guide vaccination strategy when an effective vaccine against novel coronavirus SARS-CoV-2 is found.

What happens if the COVID-19 Immunity Task Force quickly finds that background immunity against SARS-CoV-2 is very low?

Many of the current physical distancing measures will have to remain in place. Some adjustments may be possible with two caveats. First, risks vary. Policy-makers and public health experts will have to determine whether restrictions are lifted for certain groups of Canadians who are at low risk of severe COVID-19 illness – such as younger individuals – even as strong protections are maintained for the more vulnerable. And second, no matter how and when restrictions are lifted, provincial and territorial public health teams will need to do very aggressive testing and tracing to identify and rapidly control every community outbreak of the novel coronavirus.

And does the COVID-19 Immunity Task Force keep working if the background immunity is low?

Yes, but we will scale back some of our field studies and use long-term follow-up studies and laboratory studies to delineate what we can tell individuals about their immunity, especially individuals in essential jobs that involve a lot of contact with the public.

You have drawn a distinction between policy decisions and individual decisions. Are there different considerations for individual decisions?

Yes. The basic problem is that viral immunity is complicated. To a given person, a positive quick test using one of the kits on the market conveys this message: “Yes, it looks like you have been exposed to the novel coronavirus SARS-CoV-2 because you have antibodies in your blood that seem specific to that virus.” However, we do not know the level of those antibodies, how long they will remain elevated, or how closely the level of antibodies correlates with protection against a serious infection in the future.

In fact, the body’s protection depends not just on antibodies but on specialized cells that are essential to viral immunity. Testing this cellular immunity is complicated, but it is important if we really want to make sense of immunity at an individual level. This is why the Task Force will support three types of studies. It will do fast cross-sectional studies of different populations, regions and communities; these studies will help with policy decisions. It will follow groups of people with and without past novel coronavirus infection over time, repeating more detailed blood tests to understand how their immunity is evolving. And it will also support some laboratory research to figure out the best and most efficient tests that will help us make decisions about policy and as individuals.

This sounds as if we cannot just issue a ‘perpetual and perfect immunity passport’ based on a quick blood test for antibodies against the novel coronavirus SARS-CoV-2. Is that correct?

Correct, based on our limited knowledge to date. We can confirm when someone has been exposed and has some immunity. That is valuable information. But we cannot currently provide an iron-clad guarantee that they will not ever get COVID-19 disease. That is a key reason why the Task Force will be supporting more research into how immunity develops, how complete it is, and how long it lasts. We will also be looking to see if other tests can give us a clearer picture and more certainty about individual results.

For now, however, it is important for information to be generated that will help Canadians understand what their individual immunity tests mean. The Task Force will be analysing these issues carefully. For example, we know that the risk of severe COVID-19 varies according to several well-proven factors, including age, obesity, diabetes, and other medical conditions. Someone with, say, a positive screening test for antibodies who is 40 years old and entirely healthy, may justifiably have a very different view of their risk than someone else with the same test result who is 70 and has multiple health problems. Our work-plan includes providing timely and relevant information to public health officials and clinicians who will be advising the general public and individuals on the interpretation of results of immunity tests.

Let us turn to the funding and function of the COVID-19 Immunity Task Force. These large field studies sound expensive. Why would we spend a lot of money on this work rather than studies of drugs or development of vaccines?

First, if this information helps restart even part of the Canadian economy a week or two earlier than would otherwise be the case, the return on investment will be enormous.

Second, this funding is entirely separate from the funding for clinical trials of drugs to treat COVID-19. The Government of Canada is continuing to make major investments in those drug trials.

Third, the Government of Canada is already reviewing several applications from Canadian groups seeking funds to move ahead with novel coronavirus SARS-CoV-2 vaccine development. The Task Force’s funds do not encroach in any way on those funding streams.

Finally, if a drug is tested carefully and proven effective against COVID-19 disease in, say, three European countries, we can safely adopt that drug for use here to help Canadians. If a safe and effective vaccine is developed first in the US, we can also use that vaccine here. There is no similar situation for measures of background immunity to the novel coronavirus SARS-CoV-2. We cannot assume that what is true in Italy – a small and very densely populated country with unique demographics – will be true in rural and northern communities in Canada when it comes to the proportion of people who have some immunity to novel coronavirus SARS-CoV-2.

In short, the COVID-19 Immunity Task Force is not supporting conventional research studies. We are trying to facilitate rapid-fire information gathering on an efficient basis. To that end, all partners will be expected to share data with each other and inform policy decisions and the Canadian public. More information about the Task Force’s operating principles can be found on our website.

You have emphasized that the COVID-19 Immunity Task Force will be supporting a lot of laboratory work as well as epidemiology studies to understand immunity to the novel coronavirus SARS-CoV-2. How will you make sure the laboratory work is done properly?

The Leadership Group includes several distinguished scientists with world-class expertise in laboratory and clinical immunology research. Among them is Dr. Charu Kaushic, Scientific Director of the CIHR Institute of Immunity and Infection. The Task Force will quickly set out a series of specific and practical questions about COVID-19 immunity and immunity testing. We have structured an arrangement with CIHR and Health Canada that will enable an extremely rapid CIHR-supervised review of proposals to provide the best possible answers to those questions in specified timeframes. The Task Force will work closely with the world-renowned National Microbiology Laboratory [NML] in Winnipeg and will receive information from all evaluations of tests and testing devices undertaken by NML and the Health Protection Branch of Health Canada.

Multiple institutions, agencies, provinces and research groups are now keen to do immunity testing. Hospitals want to test their front-line clinical staff, and blood banks are also testing donations for antibodies to the novel coronavirus SARS-CoV-2. What does the COVID-19 Immunity Task Force add?

A core operating principle for the COVID-19 Immunity Task Force is partnerships. We are not interested in competing with others. On the contrary, our modus operandi will be to support partners that are best suited to carry out studies that address the practical issues in immunity to novel coronavirus SARS-CoV-2 identified by our Leadership Group. And we fully expect that provinces, regions, institutions, and existing research teams will be asking many of the same questions. Partnering with them will achieve three positive goals.

First, everyone’s dollars will go further. That is obviously true because the Task Force can co-fund projects. The Task Force as a clearing house can also help quantify the demand for testing across many studies which are getting started or underway. That will put Canada in a stronger position to negotiate priority and price with test manufacturers, as well as insisting on performance standards.

Second, the work can go faster and further if unnecessary duplication is avoided, and if everyone shares ideas on design and deployment of studies. The Task Force secretariat will also search worldwide for existing protocols, looking for best practices, and sharing them as soon as they are found.

Third, as we have said before, some harmonization of methods and data-sharing will help to boost sample sizes rapidly and generate more reliable assessments of COVID-19 immunity across a wide range of Canadians. That information, in turn, will help inform decision-makers and other key stakeholders across the country in a timely fashion.