Coronavirus (COVID-19) testing: Can serological or antibody testing  really confirm  immunity?

Filed Under: Costs

 

By MOLLY TAFT, PHOEBE PINDER and JEANNE PINDER

How do we get back to normal from coronavirus? There’s a lot of talk about serological tests, sometimes called antibody tests, that can show immunity from the virus – you may even have seen some advertisements for tests that you can buy. But do these tests work? Here’s what you need to know.

What’s a serological test?

Serological tests measure the amount of antibodies present in the blood in response to a particular virus – in this case, SARS-CoV-2, the virus that causes COVID-19. The presence of specific antibodies in the blood indicate a prior infection, whether or not a person experienced symptoms. These antibodies for SARS-CoV-2 seem to typically appear within the second week after onset of symptoms,  making this type of testing ideal for detecting prior infection, according to the World Health Organization. Nasal swab tests, by contrast, seek to detect active infections. 

Researchers hope that antibody tests will not only be more accurate than the nasal-swab tests, but that they could help provide a clearer sense of the number of asymptomatic coronavirus cases in the country. 

The widespread availability of a serological test that could tell if someone is immune is a tempting idea – with the thought that it might confer a “golden ticket” type situation to allow countries to open back up and immune people to return to work.

The situation is complicated by the fact that the nation – and the world – is in a panic. Public health officials, businesses, and ordinary people are looking for answers in an uncertain situation, hoping for a test that has a definitive answer.

But experts disagree on how accurate the tests actually are, and caution on relying too heavily on serological testing at this stage in the pandemic.

How do they work – and do they work?

When a person comes down with a virus, the body produces specific antibodies in response, which are capable of recognizing and attacking that virus. In some cases, such as with chickenpox and measles, these antibodies will provide life-long protection against the virus, making a person essentially immune to reinfection after being infected once. 

Other viruses, such as human immunodeficiency virus (HIV), do not provide any protection after initial infection. Immunity is a spectrum, and not all viruses are created equal. 

COVID-19 is still new, and researchers are scrambling to gather more information on how it behaves while comparing it to similar viruses. SARS-CoV-2 is part of a large family of viruses (coronaviruses) that cause upper respiratory tract illness. Some of these viruses are as mild as the common cold, but others, specifically SARS, MERS, and now SARS-CoV-2, are particularly deadly.

Right now, researchers can only turn to previous studies of related viruses to try to find answers about immunity to SARS-CoV-2. Prior studies of SARS and MERS indicate that antibodies for these viruses remain in the blood for 2 or 3 years, respectively, after initial infection. However, neither of these studies determined if the presence of antibodies actually provided protection against reinfection. 

Another earlier study, from a British hospital, found that people infected with a coronavirus that caused a common cold were immune to that exact strain of virus the following year, but had no immunity to a slightly different strain of the same virus. Researchers can make predictions and assumptions based on these studies of other coronaviruses, but  only time will provide us with definitive answers about SARS-CoV-2. The virus itself has been known for barely 6 months, so suggesting that antibodies confer lifelong immunity is, of course, not possible.

The antibody tests themselves are also far from sufficiently accurate. Studies have reported high rates of false positive results, in which the test was not able to differentiate between antibodies for SARS-CoV-2 and those for other types of similar coronaviruses, as well as high rates of false negative results, in which the tests were not able to detect antibodies in people who had had mild cases of COVID-19, France24 reported. 

The ideal scenario would be a case in which an infection with SARS-CoV-2 provided total immunity, at least for a period. David Walt, a professor of pathology at Harvard Medical School and Brigham and Women’s Hospital in Boston, told Bloomberg News that there has been some recent, hopeful evidence that SARS-CoV-2 triggers the production of neutralizing antibodies (antibodies that detect and attack a given virus) in infected individuals, like a recent study in China, which found  found that blood-plasma transfusions containing antibodies from people who had recovered from COVID-19 improved the condition of 5 patients who were critically ill with the virus.

But “there is no proof at this point that the development of an antibody response will be protective,” Walt warned Bloomberg. “There is no evidence yet that people can’t be reinfected with the virus.” 

Colin West, a physician with the Mayo Clinic, described his reservations about serological tests in an interview with Clear Health Costs:

“Antibody tests can sometimes cross-react with other antibodies resulting from other diseases. Laboratories are working incredibly diligently to try and get an antibody test that is very, very specific to a COVID-19 infection. But if any other virus or any other exposure also maps to generate that same kind of antibody, the test is going to pick that up as well. 

The hope is that that’s not going to be terribly common and that there won’t be too many, you know, cross-reaction issues. But I go back to the data on test performance. We haven’t seen nearly enough of the details yet. 

The other thing about the antibody testing is as I mentioned a moment ago: It tells us ideally, that someone’s been exposed. It doesn’t say that much about the level of their exposure. It doesn’t say whether they were infected to a point that leads to immunity. It doesn’t say how perfect that immunity is. 

And then a final point people have not talked about a lot with Coronavirus:  if you were exposed and you build antibodies, are you immune only to that same strain of the Coronavirus? What if it mutates? Are you still immune? Or is it like influenza where you might have partial protection from some other strains? 

And all of this is such early days that we just don’t know.”’

If we’re not sure that the tests work, why are they available?

Despite this gray area, serological tests are quickly coming on the market – with the blessing of the federal government.

“The Food and Drug Administration, criticized for slowness in authorizing tests to detect coronavirus infections, has taken a strikingly different approach to antibody tests, allowing more than 90 on the market without prior review, including some that are being marketed fraudulently and are of dubious quality, according to testing experts and the agency itself,” Laurie McGinley writes in The Washington Post.

Only a very few blood tests have received FDA approval for use, under something called the Emergency Use Authorization. FDA Commissioner Stephen Hahn told the Washington Post that only four tests have gotten authorization from the FDA: Cellex, Chembio Diagnostic Systems, Ortho Clinical Diagnostics and Mount Sinai Laboratory.

But a number of other serological tests have been developed and are available for use, despite not being authorized by the FDA. Health departments, clinics, health systems and others have bought these tests to do antibody surveys, but their reliability is not certain.

“In March, the FDA issued a policy to allow developers of certain serological tests to begin to market or use their tests once they have performed the appropriate evaluation to determine that their tests are accurate and reliable,” the agency said in a statement in early April. “This includes allowing developers to market their tests without prior FDA review if certain conditions outlined in the guidance document are met.” 

The FDA “has allowed about 90 companies, many based in China, to sell tests that have not gotten government vetting, saying the pandemic warrants an urgent response,” Steve Eder, Megan Twohey and Apoorva Mandavilli wrote for The New York Times April 19. “But the agency has since warned that some of those businesses are making false claims about their products; health officials, like their counterparts overseas, have found others deeply flawed.

The Times article added: “Tests of ‘frankly dubious quality’ have flooded the American market, said Scott Becker, executive director of the Association of Public Health Laboratories. Many of them, akin to home pregnancy tests, are easy to take and promise rapid results.”

What could happen if these tests become widespread before the science catches up?

Already, countries like Chile and Germany have announced plans to kickstart programs that would test residents for immunity, with Chile saying it will provide “passports” to citizens deemed immune.  But experts say total faith in antibody testing as a solution would be very misguided at this point – despite businesses’ rush to mass-produce tests. 

“A test is only as good as its results,” Kelly Wroblewski, director of infectious disease programs at the Association of Public Health Laboratories, which has been urging the FDA to take a closer look at the unapproved tests, told the Washington Post. “Having many inaccurate tests is worse than having no tests at all.”

Yet there is a deep desire to get tested by people looking for certainty, much like what happened with the swab test – though we know it has maybe a 70 percent accuracy rate in some cases. Many doctors advise people to  continue to practice social distancing, wearing masks, washing hands and  taking other precautions regardless of test results either with a swab or a blood test. 

Even if an effective test is developed, it could change American life as we know it. Donald McNeil imagines for the New York Times:

Imagine an America divided into two classes: those who have recovered from infection with the coronavirus and presumably have some immunity to it; and those who are still vulnerable.

“It will be a frightening schism,” Dr. David Nabarro, a World Health Organization special envoy on Covid-19, predicted. “Those with antibodies will be able to travel and work, and the rest will be discriminated against.”