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How serological COVID-19 tests work — and what their results mean

Serological testing examines a person’s blood looking for antibodies to the disease.

blood sample for serological test
For most people who get serologic tests, the process is much like having blood drawn.
REUTERS/Christian Hartmann

Last week, Gov. Tim Walz announced a $36 million partnership with the Mayo Clinic and the University of Minnesota to test as many as 20,000 Minnesotans daily for COVID-19.

So far, the type of test that’s gotten the most attention is the molecular testing, which can tell Minnesotans if they’re currently infected with COVID-19. These tests have been available — though in short supply — for months in Minnesota, and more than 70,000  tests of this type have been performed among the state’s residents.

Newer to Minnesota is serology testing, which determines whether someone was previously infected with COVID-19 based on antibodies to the virus in their blood. As the state gets its serological testing going, here’s how these tests work and what they can and can’t tell us about COVID-19 in our state.

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How do I get a serologic test?

These tests aren’t widespread yet, but you can call your medical provider to see if the test is available and if so, if you’re eligible for it.

Be wary of tests offered outside a clinical setting. The Food and Drug Administration relaxed its review process for serological tests in the interest of making them available quickly, and lots of the tests on the market are plagued with inaccuracy. Some even claim to have been reviewed or authorized by the FDA when they haven’t.

Research by the University of California San Francisco and UC Berkeley testing the accuracy of some of the more than 120 serological tests on the market found some had false positive rates higher than the share of people infected in communities. 

What happens when I get a serological test?

For most people who get a serologic test, the process is much like having blood drawn. A phlebotomist inserts a needle to get a sample, which is sent to a lab.

Once a patient’s sample gets to the lab, blood serum is separated from red blood cells.

Blood serum, unlike the bright red blood we’re more familiar with, is a whitish-yellow color. The serum contains white blood cells, antibodies, fluids and other parts of the human immune system, said Sara Vetter, the Minnesota Department of Health’s Infectious Disease Laboratory Manager.

The COVID-19 test looks for antibodies to the disease in the serum. Antibodies are blood proteins your immune system makes to fight a virus.

Like a puzzle piece, an antibody matches perfectly with a virus or bacteria it’s encountered, Vetter said. “It allows your immune system to recognize that antigen — that bad bug — as something bad and then it allows your immune system to quickly take care of it and destroy it.”

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Because antibodies are so specific to the bug they were made to fight, having COVID-19 antibodies in your blood means you were infected with the virus.

There are different kinds of antibodies. Immunoglobulin M, or IgM antibodies develop quickly in response to a bug to help with early immune response, while Immunoglobulin G, or IgG antibodies develop later.

“That’s what’s called the memory response. Those are the antibodies that typically stay around a long time and are activated when you get re-exposed to that virus or bacteria again,” Vetter said. It typically takes between two and three weeks for people to have detectable levels of IGG antibodies, which is what the tests typically look for.

Some rapid tests look for IgM antibodies, but those can only tell if someone has been recently exposed.

REUTERS/Christian Hartmann
REUTERS/Christian Hartmann
A phlebotomist inserts a needle to get a sample, which is sent to a lab.
How can the test tell if I have antibodies?

In the lab, a plate containing small wells is coated with the SARS-CoV-2, or novel coronavirus, antigens. That’s topped with blood serum.

If there are antibodies in the blood that match the antigen, they stick.

Labs use a process involving enzymes that react with a chemical agent and change color if the result is positive.

“We put it in a machine that measures the color, and so the more color you have, that would indicate that there’s a positive antibody in there versus if it stays clear, then it’s negative,” Vetter said.

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How accurate are these tests?

At Mayo, 100 percent of hospitalized patients tested positive in a serological test 14 days after the onset of symptoms, said Elitza Theel, director of Mayo Clinic’s Infectious Diseases Serology Laboratory.

But with blood tests, there is a possibility for false positives.

How does that happen? Again let’s go back the puzzle — something lots of us have re-familiarized ourselves with in recent weeks.

“You’ve done this before, right? Where you’ve done a puzzle and you’ve sort of like wedged a piece in there and you think it fits, but then you find the piece that does match,” Vetter said.

That happens with antibodies and antigens too. Sometimes antibodies that don’t really match the antigens stick anyway, leading to a false positive. False positives are more common when there’s a low prevalence of disease in the population.

Theel said 97 percent of patients who have not been infected with SARS-CoV-2 test negative on Mayo’s antibody test.

If a serologic test finds I had COVID-19, can I go back to living my life?

No. And here’s why:

Having been infected or vaccinated against lots of diseases, like measles or rubella, confers long-lasting immunity. That’s because those diseases don’t change very quickly.

Others, like the flu, are shapeshifters, changing their genetic code, thwarting human immune response.

We simply don’t know enough about COVID-19 to know whether someone who has been infected can be re-infected, and how long it would take for that to happen, Theel said.

When it comes to other human coronaviruses, like SARS and MERS, antibodies are detectable for two to three years after infection.

“But then they drop off and become undetectable. So whether that’s the same thing that we’re going to see with SARS-CoV-2, we just don’t know yet,” she said.

So what are these tests good for?

Until we know more about our bodies’ immune response to COVID-19, there are a few main applications for serology tests.

The first is to determine seroprevalence — how many people in the population have been exposed to this virus. That’s important both for shaping public policy responses and better understanding the virus and how it spreads.

Another important use is to identify people whose blood contains antibodies, who can become convalescent plasma donors. Injecting the plasma of people who have recovered from the disease into the very ill has shown some promise as a treatment.

As potential vaccines are developed, serologic testing can help determine how well they work.