“We have one way to go,” when testing antibodies, Fauci warns
Antibody tests for coronavirus have rolled out in the US amid officials’ hopes that they will reveal who can get back to work – but “we have one more way to go” before the tests can really tell us, Dr. Anthony Fauci told Good morning America.
“The assumption that with the tests out there, if you have antibody positivity, you’re ready to go,” the leading infectious disease specialist said Monday.
“Unless that test has been validated and you can demonstrate an association between the antibody and the protection, it is believed that this is something we can work with.”
He noted that only a handful – four, to be precise – of coronavirus antibody tests had been approved by the Food and Drug Adminstration (FDA), and there is little clarity about the reliability of others.
In addition, scientists have not had the chance to track down enough people who have recovered from the coronavirus long enough to know for sure whether those antibodies provide immunity to reinfection, or for how long.
Dr. Anthony Fauci warned Monday on Good Morning that antibody testing does not yet reliably indicate who has developed immunity to coronavirus, and that it would be an “assumption” to say that someone is protected against antibodies by antibodies.
“We don’t know how long that protection lasts, if it lasts,” said Dr. Fauci.
“Is it a month, three months? Six months? A year?’
Dr. Fauci previously admitted that the interpretation of the results of COVID-19 antibody tests is based on assumptions.
“It is a reasonable assumption that this virus does not change much. If we get infected now and it comes back in February or March, we think this person will be protected, “he said in a JAMA webcast attended by Stat news.
Instead of a solid foundation of information about this virus and the antibodies we develop on it, “Sometimes you have to act historically,” says Dr. Fauci.
That historical basis is research into antibodies developed against other coronaviruses, including the close relative of COVID-19, the virus that causes SARS.
Humans do develop antibodies that work against these viruses, but the duration of protection varies.
Officials look forward to testing antibodies to indicate when the US can lift restrictions during protests to reopen the US
For the viruses that cause colds, the immunity is fairytale and short-lived.
But against the SARS virus, antibodies develop within a few weeks and can last for years.
This evidence informs the educated guess that antibodies we develop against COVID-19 will provide some protection, but it is by no means evidence.
And even the best blood tests for antibodies – or serological tests – can’t tell us that yet.
“At this time, we have no evidence that the use of a serological test can demonstrate that a person is immune or protected from reinfection,” said Dr. Maria Van Kerkhove of the World Health Organiazation during a briefing last week.
A Columbia University expert told DailyMail.com that it could take years to find an antibody test accurate enough.
But they added that scientists are desperately trying to find a blood test at ‘lightning speed’ within a few months.
Dr Susan Whittier said the challenge in making an antibody test lies in identifying the exact antibodies produced by the body to fight the infection.
It’s important to understand how the virus itself triggers a healthy immune system to start producing antibodies, and scientists are divided about its behavior.
This results in antibody tests of different designs, some of which did not work accurately enough because they are not specific enough for SARS-CoV-2.
Doctors also say it is unclear at this stage how many antibodies in the blood provide immunity and how long that protection lasts.
Some early animal studies suggested that antibodies could block reinfection for at least two weeks.
But research on the close relative of the new coronavirus – SARS – shows that a patient produces antibodies that last an average of two years.
Dr. Whittier said the crux of the matter is “we don’t know what we don’t know.”
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
HOW DO ANTIBODE TESTS WORK AND WHY IS IT DIFFICULT TO MAKE A RELIABLE TEST?
The development of an antibody test requires some knowledge of the proteins that make up the coat of the virus.
Viruses are made up of many proteins called antigens, some of which are shared with other viruses. Only a few may be unique to the specific virus.
The proteins specific to the virus will cause the production of antibodies that neutralize the virus, making it unable to replicate.
“ We need to find out what part of the virus will really be specific to that virus, ” said Dr. Whittier, head of Columbia University and the New York Presbyterian microbiology lab, at DailyMail.com.
Those sections of the viral protein coat must then be produced in the laboratory using cell lines to be tested in an immunoassay.
Scientists take that protein, place it on the bottom of a plastic well and put the blood serum in it and see if there’s anything sticking to it, “said Dr. Whittier.
That “something” would be the antibodies in the patient’s blood.
Anna Petherick, a public policy lecturer at Oxford University, said immunoassays will form the basis of home testing kits for people who think they have had COVID-19.
“But their development takes time,” she explained The Lancet.
‘Expressing the protein in the right structure is often the most difficult step.
“In a non-system, such as a bacterial cell, the complex protein structures can come out somewhat distorted, enough to prevent antibodies from recognizing them as they would be the original viral coat protein.
‘There are also questions about which antigens (proteins) are best for this.
“Some diagnostic developers are reluctant to give away too much detail, although the viral peak protein is widely considered to be the obvious candidate.”
Different labs that perform antibody tests may not even test for the exact same antibodies.
Some tests may confuse antibodies produced in response to the virus that causes COVID-19 with those for other coronaviruses.
“There are many other coronaviruses, and the problem is that you need to know which target is specific to this virus, so it’s not going to respond crosswise,” said Dr. Whittier.
Normally, finding the right target takes “ months or years, and we try to do it in weeks to months, ” said Dr. Whitittier.
“We don’t know what specific antigens or targets to look for.
“It seems to the lay public as if it takes a long time, but from a laboratory perspective it is happening very quickly.”
Labs test specific antigens by using the blood of patients who have been confirmed to have the infection.
It will reveal whether the antigen they have identified causes the antigens to stick. If not, it is not correct.
“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, ”said Dr. Whittier.
But only 50 percent of patients should have had antibodies.
“So if it was positive, that was good, then they definitely have antibodies.”
But if it were 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 tests, because maybe perfect is the enemy of good.”
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
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.
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
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.
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 made 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.
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.
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.
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 critical ingredients for an antibody test. They tell scientists 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,” said Dr. Whittier.
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.
Dr Whittier said, “Twelve to fourteen days most individuals have an antibody response, but we don’t know if it’s protective and we don’t know how long it will last.”
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 as to whether antibodies were present. They did not reveal what volume a person’s body had produced.
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.
.