Why is it so difficult to make a reliable coronavirus antibody test?
Antibody tests for coronavirus that can indicate who had the virus and are now immune to it are popping up all over the U.S. and government officials have listed these blood tests as the key to reopening the nation.
But there’s little clarity about how reliable or accurate these tests – which screen for infection-fighting proteins called antibodies that a person develops after they’ve already been infected with coronavirus – are real.
Some early animal studies suggested that antibodies could block reinfection for at least two weeks.
While that research was promising, the reality is that we just don’t yet know what level of antibodies is needed to prevent reinfection, or how long that immunological armor could last.
So even a test that accurately detects antibodies developed against the virus wouldn’t necessarily tell us that much about who’s immune, or for how long.
Labs in the United States are producing antibody tests for coronavirus hoping to determine who has developed immunity – but their accuracy varies widely due to relaxed FDA regulations in the interest of faster testing. Pictured: Drive-thru antibody test set up by USC
ANTIBODIES OFFER IMMUNITY – BUT HOW MUCH PROTECTION AND HOW LONG IT WILL LAST
When we catch an infection, the immune system works to make specialized weapons against the intruder we came into contact with, called antibodies.
Once we have come across a pathogen and have developed antibodies against it, these proteins sound the alarm when the invader returns and neutralizes them.
HOW DO ‘STRIP’ BLOOD TESTS WORK FOR CORONAVIRUS?
Simple coronavirus blood tests, such as Premier Biotech’s, work just like pregnancy tests.
After the blood sample is collected, a technician injects it along with some buffer into the analyzer – which is about the size of an Apple TV or Roku remote – and wait about 10 minutes.
Draw the blood drop and buffer into the absorbent strip of paper contained in the plastic collection device.
Blood naturally seeps down the strip, which is painted at three points: one for each of two types of antibodies, and a third control line.
The strip is marked ‘IgM’ and ‘IgG’, for immunoglobulins M and G. These are all types of antibodies the body produces in response to a late or early infection.
Along each strip, the antibodies themselves are pressed in combination with gold, which reacts when either the antigen – or the pathogen, in this case the virus causing COVID-19 – or the antibody fighting, is present.
Results are presented in a similar fashion to that of a home pregnancy test.
One line – the top control strip – means negative.
Two lines – the upper control line and the lower IgM line – in a spread configuration means that the sample contains antibodies that the body begins to produce shortly after infection.
Two lines closer – control and IgG – together mean that the person is positive for the later antibodies.
Three lines indicate that the patient is positive for both types of antibodies.
But not all antibodies are created equal, and not everyone develops the same number of antibodies.
For example, it is known that once you get chickenpox you are almost certainly immune to it and will never be infected again.
This does not apply to antibodies against other pathogens. Immunity to other infections disappears relatively quickly.
Flu is fairly well understood, but the virus has many strains that mutate easily.
Antibodies produced against every variation of flu we come across are quite specific to that unique infection.
So when we come into contact with an evolved or other strain of flu the following season, the antibodies we developed the year before don’t do us much good.
That’s why flu vaccines are ‘recombinant’ – they are created from a combination of different flu strains, triggering the production of a variety of antibodies to block the strains scientists think we can go around the world that year .
The most common coronaviruses, which cause a seasonal cold, cause a fairly weak antibody response, which lasts only a few weeks, which is part of the reason you can catch multiple colds in one year.
However, research into the close relative of the new coronavirus – SARS – is somewhat more encouraging. In the second week after someone got infected, they generated antibodies that seem to last an average of two years.
But we just don’t know how antibodies to the virus that causes COVID-19 will behave because we know it’s only been four months.
HOW DO ANTIBODE TESTS WORK AND WHY IS IT DIFFICULT TO MAKE A RELIABLE TEST?
To make an antibody test, scientists must first find out what part of the virus antibodies are made on it.
But viruses are made up of many proteins, some of which are shared with other viruses, and only a few are unique to the specific virus scientists they want to test.
“We need to find out what part of the virus is really specific to that virus, take that protein, put it in the bottom of a plastic well and put the blood serum in it and see if there is anything sticking,” Dr. Susan Whittier, head of Columbia University and the New York Presbyterian microbiology lab, at DailyMail.com.
The blood of someone who has already had coronavirus reacts with the strips to the test if they have developed antibodies, but several tests look for an immune response to different components of the virus
The more Americans are infected, the more antibodies can be tested and monitored to see if they have developed enough antibodies to protect them from reinfection and how long that immune shield will last. On Tuesday, it was confirmed that more than 604,000 people in the US had coronavirus
“There are many other coronaviruses, and the problem is that you need to know which target is specific to this virus so it doesn’t cross-react.”
Thus, different labs that perform antibody tests may not even test for exactly the same antibodies, and some tests may confuse the antibodies produced in response to the virus that causes COVID-19 with those that neutralize other coronaviruses.
Usually it does ‘it takes months or years, and we try to do it in weeks to months,’ said Dr. Whitittier.
The New Hampshire test (photo) looks for the presence of antibodies, but it cannot say what level of antibodies are in a person’s blood, and scientists don’t know how much is enough to provide protection against reinfection
“We don’t know the specific antigens or targets” to look for.
If a lab thinks it has found the specific antigen, it then tests the sensitivity of the test, but patients’ blood allows the test to confirm the infection.
“At Columbia, we validated an antibody test developed in Asia and performed many of our tests [blood] serum we had from patients and it turned out to be very specific – it only picked up SARS-CoV-2, which is good – but it was only 50 percent of patients who should have had antibodies, “said Dr. Whittier.
“So if it was positive, that was good, they definitely have antibodies,” but if it was negative, “you might as well toss a coin.”
Needless to say, Columbia dropped that test.
And since the FDA guidelines have been relaxed in an effort to run more tests faster, there is less certainty that validation is being conducted with an extensive sample of patients.
Dr. Whittier says the package insert for one test she looked at said the company had tested their test on only about five patients.
“That’s crazy,” she said.
‘Normally that would never happen, but in the middle of a pandemic you can push out assays, because maybe perfect is the enemy of good.
“It seems to the lay public as if it takes a long time, but from a laboratory perspective it is happening very quickly.”
WHAT DOES A POSITIVE CORONAVIRUS ANTIBODE TEST REALLY MEAN? EVEN THE EXPERTS DON’T KNOW – YET
Time and volume of infected people are two important ingredients in translating the meaning of an antibody test – how many antibodies are enough to make someone immune to reinfection and how long that immunity lasts.
And labs that develop antibody tests don’t have either.
“We can’t tell you because we don’t have a gold standard to compare it to.”
On April 2 – less than two weeks ago – the FDA authorized emergency use of the first coronavirus antibody test in the US.
That’s about as long as scientists think it takes a patient to set up an antibody response to SARS-CoV-2.
“Twelve to fourteen days is when most people have an antibody response, but we don’t know if it’s protective and we don’t know how long it lasts.”
The antibody test is the first step to answer those questions. But some people will develop antibodies faster than others, and some will develop larger amounts of antibodies than others.
It will be necessary to follow these people and test them repeatedly to find out what the ‘gold standard’ for immunity is.
In addition, the initial antibody tests only yielded results about the presence or absence of antibodies, not in what volume a person’s body had produced them.
Now laboratories are starting to produce ‘semi-quantitative’ tests, which can tell if someone has ‘a little antibody or a lot of antibody,’ said Dr. Whittier.
As more people are tested for levels of antibodies, not just their existence, epidemiologists can study which levels provide protection and for how long.
But for now, “we don’t know what we don’t know,” says Dr. Whittier.
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