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The Great COVID-19 Immunity Test Kit

In the face of ever-changing policies around COVID-19 risk, couldn’t we simply test people to see how at-risk they really are?

The kit arrives in the mail. You swab the inside of your cheek and mail it back. Two weeks later, the company emails you a report. You are told you have a 2% risk of getting COVID-19 and a 5% chance of passing the virus on to another person. The report claims these risks will never change. You decide that the risk is low enough and return to your pre-pandemic lifestyle.

This scenario will appear fanciful to many, and it should, but I have been asked versions of this storyline in question form since the vaccines were rolled out. Is there a test, people wonder, that reliably tells you what your risk for COVID-19 is, some scientific assessment to overrule the perceived “inconsistent” and “convoluted” public health rules based on vaccines, boosters, variants, and activities? A cheek swab, saliva test, or blood draw that would zero in on a deterministic bit of biology to classify you as low risk, medium risk, or high risk? A personalized and accurate immunity passport, regardless of your vaccination status?

It’s not a completely silly idea. There is something comparable being explored in hospitals for people who already have the disease.

The idea is to find some biological marker that predicts how well they will do, what is called a prognostic biomarker. Scientists have reported preliminary findings, like looking at the volume of red blood cells, measuring the levels of antibodies directed against molecules released by dead blood cells, and gauging the amount of mitochondrial DNA circulating in the blood. There is even a kit sold in India that claims to be able to identify the risk status of hospitalized COVID-19 patients by sorting their blood cells and looking for a signature.

Many of these biomarkers, though, are in the early stages of the research process. They may not pan out in the end. They tend to be associated broadly with disease as a whole or with death from any cause. Also, they were found by looking at groups of people and seeing that, on average, people with this marker are more likely to do poorly, but they may not be useful as a predictor for an individual. And, more importantly for us, they cannot be useful if you do not already have the disease.

So what could be measured to assess our protection against COVID-19? The obvious answer is antibodies. When confronted with a dastardly invader like a virus, a branch of our immune system produces antibodies to specifically bind to, identify, and neutralize the intruding microorganism. In fact, detecting antibodies against the coronavirus is the way in which doctors can know that you have been infected by this virus before. So it would stand to reason that a simple risk assessment tool would examine our blood: the presence of anti-SARS-CoV-2 antibodies would mean immunity; lack thereof would indicate danger. Would that it were so simple.

Immune from certainty

Two fantastic pieces in The Atlantic, one by Katherine J. Wu and the other by Ed Yong, summarize the problem with this superficial logic: immunology is where intuition goes to die. The amount of anti-SARS-CoV-2 antibodies circulating in our blood do go down, a finding which led to alarming headlines about “waning immunity,” but it doesn’t imply that our protection is falling. If our cells kept secreting massive amounts of antibodies after every infection for the rest of our lives, our blood would turn to molasses. Fewer antibodies remain after an infection, but this is because antibodies are just one of many weapons used by our immune system to fight off an invasion.

A paper published in the journal Science in February of this year gives us a window into the complexities of our immune system following an infection by the novel coronavirus. The researchers looked at immune cells from 188 people more than six months after getting COVID-19. We might expect that all of these people are now immune to the disease and that their immune cell profile would be identical. And while the results showed that a durable immunity against contracting COVID-19 again was “a possibility for most individuals,” what the scientists saw in their blood was actually highly variable. It was not identical. The memory of an infection resides with our antibodies, yes, but also with our memory B cells, memory CD4+ T cells, and memory CD8+ T cells, and how all of these miniature soldiers and their immunological weaponry work together is still poorly understood. Reinfection, for example, appears to be possible though rare.

Measuring antibodies against the coronavirus in our blood is simply not enough. The researchers behind the Science paper concluded that those levels did not vary hand-in-hand with another part of our immunological memory, and that simple tests to measure these antibodies “do not reflect the richness and durability of immune memory to SARS-CoV-2.”

I reached out to Professor Judith Mandl, Ph.D., an assistant professor in McGill’s own department of physiology and the Canada Research Chair in immune cell dynamics. Is there anything we can reliably measure to indicate how well protected we are from the coronavirus? “We still do not have a full picture,” she wrote to me, “of what the ‘correlates’ of protection might be. Whether or not antibody levels or the level of T-cell responses, for instance, provide this information remains an open question of study.” It is likely, she added, that high levels of antibodies against the virus do mean you are protected from the disease. If these levels are still high a year later, you can feel confident, she told me, that you still have immunity against the strain of the virus that made you sick and that you possibly have some protection against the strains circulating now, though how much remains an open question.

But these inferences are not cast in stone, and the opposite—that low levels of antibodies must mean poor protection—may not be true. To echo the saying that punctuated Ed Yong’s article, the immune system is very complicated.

As for whether or not this mythical test kit of ours could evaluate how much of a risk we are to other people, meaning how likely we are to transmit the virus even if it does not make us sick, Professor Mandl was clear: no. Let’s imagine we test the amount of virus present in our saliva. A high amount means we are contagious, a low amount means we are not. “This level can change in a matter of hours, so the test would already be wrong,” she told me.

The truth is that we already know who is at risk for severe outcomes from COVID-19. Older adults (with the risk increasing with each decade). People with chronic medical conditions like lung disease, heart disease, high blood pressure, diabetes, stroke, kidney disease, dementia, and liver disease. People whose immune system is compromised because of specific drugs (e.g. chemotherapy) or medical conditions (e.g. cancer). People living with obesity. And, giant neon sign please, people who have not been vaccinated against COVID-19.

For more granular evaluations of risk, we then have to take into account how widespread the virus is in our community; indoor versus outdoor activities; the type of mask we are wearing (or not wearing); how many people are around us; how long the activity is; how many times we repeat the activity; and whether or not we are vaccinated. There are apps out there to help us calculate this risk (though I have not tested any of them out), but keep in mind that they will churn out rough estimates. They don’t deliver guarantees.

Risk assessment, in the best of times, is tricky. In the middle of a pandemic that threw a new and mutating virus at the tangled web that is our immune system, the calculation is even thornier, and our desire for absolute clarity and stability will often go unsatisfied. We have to learn to be nimble.

Take-home message:
-There currently exists no accurate way to determine, via a medical test, what someone’s risk is of contracting COVID-19 or of transmitting the virus to someone else
-Levels of antibodies against the coronavirus are not a reliable measure of whether or not someone is now immune to it, as the ways in which it interacts with our immune system are still poorly understood
-To evaluate our risk of catching the coronavirus or passing it on to someone else, we still have to rely on a calculation that involves health risk factors, how common the virus is in our area, how risky the activity we want to engage in is, and whether or not we and the people around us are vaccinated


@CrackedScience

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