Recently, the World Health Organization put out a buzzkill of a statement: “There is currently no evidence that people who have recovered from Covid-19 and have antibodies are protected from a second infection.”
In the United States, over a million people have been infected with the SARS-CoV-2 virus that causes Covid-19 as of April 28. Most of those people have recovered from the virus, and want to know if they’re protected going forward. Others who experienced mild symptoms or none at all may want an antibody test to see if they were infected.
At first glance, the WHO statement is confusing: Isn’t the presence of antibodies — the molecules your immune system makes to target and stop a specific virus — a good thing? Aren’t they typically the thing you need to fight off another viral infection?
They’re certainly not a bad sign. But experts in immunology and virology tell me that the WHO is right: The detection of antibodies to Covid-19 is not enough to declare a person immune because we don’t yet know how immunity to this virus works.
“We don’t yet have reliable data about protective immunity,” Angela Rasmussen, a Columbia University virologist, says. Much more scientific work needs to be done to make sure the presence of, and quality of, antibodies detected in a test confers immunity. Scientists also need to figure out how long that immunity lasts. Finally, there are also concerns about the reliability of some of the antibody tests. It’s not helpful if antibody tests have a high rate of false positives and false negatives.
All this doesn’t mean the antibody tests are useless; they may still play a crucial role in helping us understand how to beat this pandemic.
But the WHO doesn’t want anyone who tests positive for antibodies to feel like they’ve acquired a superpower. “There is not enough evidence about the effectiveness of antibody-mediated immunity to guarantee the accuracy of an ‘immunity passport’ or ‘risk-free certificate,’” the WHO says.
Positive antibody tests are certainly suggestive of immunity, but they don’t show the complete picture of immunity. Here’s what will.
Most antibody tests just test for the presence of antibodies, not the quality of them.
First off, antibodies: What are they?
Antibodies are molecules produced by your adaptive immune system. This is the system that creates and mounts an individualized defense to a particular pathogen that enters your body. Antibodies are specific: They target one antigen (i.e., a foreign infectious protein, like those found on a virus) and help clear it from our bodies. There are all sorts of antibodies. There are ones that merely tag a virus and call for other immune cells to react to it. And then there are neutralizing antibodies: These are the molecules that will prevent a virus or pathogen from infecting more of your cells.
“When you first get infected with SARS-Cov-2, it usually takes anywhere from 10 to 14 days to make antibodies that are effective,” says Vineet Menachery, an immunologist who studies coronaviruses at the University of Texas Medical Branch. “That immunity actually peaks between four and eight weeks after you’ve been infected. The antibodies are really powerful at that point.”
Ideally, doctors want to find neutralizing antibodies in someone who has recovered from Covid-19. But that’s trickier than it sounds.
“There are two main types of antibody tests,” Menachery explains. The first just looks for antibodies and can be completed in a few hours. This is called an ELISA test (short for enzyme-linked immunosorbent assay).
How the test works is kind of simple in concept. “The test relies on a plate that is coated with a viral protein of interest,” the Johns Hopkins Center for Health Security explains. Basically, the blood of a person is added to that plate, and the test just looks for whether there are any antibodies that stick to the viral protein. A positive ELISA test tells a doctor there are antibodies in the blood. But, critically, it does not tell them much about their quality.
The second test is more involved, and rarer. It’s called a serum neutralization test, and it takes a few days to process. It not only looks for antibodies, it then exposes those antibodies to a virus in a cell culture to see how effective the antibodies are in stopping the virus.
Ideally, scientists will correlate the two tests and figure out which concentrations of antibodies confer the highest level of immunity. “This work is ongoing,” Menachery says. It’s still not known what levels of antibodies are needed to have lasting, protective immunity. (Scientists are also still working out whether the presence of antibodies also means you can’t give the virus to someone else.)
Scientists will need to study immunity over time
Serum neutralization studies aren’t the only thing needed to crack the immunity code.
That’s because what happens in a little pool of blood may not always translate to what happens in the vastly complex human body. We also need further studies called “correlate of protection studies.” These are longitudinal studies that track patients over time, “following them to see if they develop reinfection; and comparing the antibody levels and other immune markers between those who are reinfected and those who are not,” Saad Omer, director of the Yale Institute for Global Health, says. “There are other study designs, but this is the overall concept.”
There have been reports of a few patients out of China who had mild symptoms of Covid-19 who did not have detectable neutralizing antibodies after recovery, though they did have another form of antibody that binds to the virus. “It’s unclear whether they have protective immunity,” Nature reports. Tracking these sorts of people long term, for instance, can help us better understand what mix of antibodies is necessary for enduring immunity.
These types of longitudinal studies take a long time to produce data. But in the meantime, researchers can also look at results from convalescent plasma therapy trials to gauge which antibodies, and in what numbers, are most likely to neutralize the virus. Convalescent plasma therapy is when parts of the blood of people who have recovered from the disease are used to treat those still experiencing symptoms. That plasma contains antibodies. And if these trials are effective, “that suggests that antibodies are capable of neutralizing virus,” Rasmussen says.
Another unanswered question: How long does immunity last?
Even if people do become immune, “one thing we don’t know about still is how long that immunity would last,” Rasmussen says. “And that’s unfortunately not something we can determine until we wait months or years in the future, and test again and see if those antibodies are still there.”
For reasons scientists don’t quite understand, for some infections, someone’s immunity never wanes. People who are immune to smallpox, for example, are immune for life: Antibodies that protect against smallpox have been found as long as 88 years after a vaccination.
Less reassuring here is that scientists have observed antibody levels for other coronaviruses (there are four coronavirus strains that infect people as the common cold) can wane over a period of years. A few weeks after an infection, antibody levels will be at their highest. But “a year from now, that number is likely going to be a little bit lower, and five years from now it’s likely to be potentially a lot lower or a little bit lower, and we don’t know the factors that change that,” Menachery says.
Adding to the pessimism: Just recently, Columbia University researchers published a preliminary study that found that some people got reinfected with a coronavirus (one that causes the common cold) within a year.
However, even if you lose the antibodies, it doesn’t mean you are again completely susceptible to the virus. Yes, none of this is simple.
There have been a few experiments where people were voluntarily exposed to a coronavirus strain that produces a common cold. These studies show it’s common for the antibodies to these other coronavirus strains to decline after a year or so.
“The majority of people that don’t have serum-neutralizing antibodies [i.e., antibodies that take out the virus], they get infected again, but they didn’t get that sick,” Menachery says. You couldn’t do this type of test for Covid-19, he adds; it’s too dangerous
Luckily, even if your antibodies against a coronavirus decline, your body has a backup plan.
Certain types of B-cells (immune system cells that make antibodies) become memory B-cells. These save the instructions for producing a particular antibody, but they aren’t active. Instead, they hide out — in your spleen, in your lymph nodes, perhaps at the original site of your infection — waiting for a signal to start producing antibodies again.
With the memory B-cells in reserve, instead of waiting two weeks or more to get antibody production going, “you’ll only have to wait maybe two or three days,” Menachery says. “So that means, yes, you can get infected again, but you may not even know you’re sick. If you do get sick, maybe it’s a very minor infection.”
Generally, he says, the more severe your infection, the more antibodies your immune system will produce, and the longer they’ll stay in your bloodstream post-infection. So, he says, “there is some concern that if you had a mild infection that your level of protection may not last long.”
People with antibodies are probably immune for at least some months. But in this pandemic, probably isn’t good enough.
All that said, antibody tests are still useful. They help a person understand if they have been exposed to the virus. And they can help our public health understanding of how to beat this pandemic.
Antibody serology (blood) tests “are giving you a snapshot,” Sarah Cobey, a scientist who models epidemiology and immunity at the University of Chicago, says. The snapshot is of how many people have come into contact with the virus. If we compare snapshots, “we can start to try to measure the impacts of different things like school closures versus workplace closures versus shelter in place, and isolation and quarantine.” To sum up: Widespread antibody testing can help us understand which public health measures are working to beat this virus.
But on the individual level, if you get an antibody test back and it’s positive, what should you do?
Well, for one, know that the tests may be of varying quality and accuracy. The Food and Drug Administration “has not reviewed the vast majority of tests on the market, and their validity, particularly point-of-care blood tests that promise rapid results within minutes, isn’t clear,” Kaiser Health News reports. More work needs to be done to validate the tests and make sure the tests can distinguish antibodies for SARS-CoV-2 and antibodies for other viruses in the coronavirus family.
But, overall, a positive antibody test “probably means that the person is likely protected from second infection,” Akiko Iwasaki, an immunobiology professor at the Yale School of Medicine, says. But it does not say whether a person is still infectious. And it does not necessarily mean that person is immune to future Covid-19 infections. Or if they are immune, it’s unclear how long that protective immunity might last.
So what should one do?
“Keeping social distancing behavior until we know better what antibody results mean is a good idea,” Iwasaki says.
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