As some countries begin
to reopen in the midst of the ongoing coronavirus pandemic, experts are racing
to ramp up the development and use ofblood tests that pinpoint people
who have been exposed to the virus that causes COVID-19 and are no longer
The tests detect antibodies, proteins made by the immune system to fight
infection (SN: 3/27/20). People who
carry antibodies specific to the novel coronavirus, called SARS-CoV-2, have been
infected previously, even if they didn’t know it. For those people, discovering that
they have these virus-fighting antibodies could raise hopes of immunity and a
return to normal life.
But scientists are also
working to uncover what these blood tests really tell us. At this point,
there isn’t enough evidence to confirm that recovered
people are protected from the disease and, if so, for how long, the World Health
Organization said in a statement on April 24. So people hoping for that assurance
may be disappointed.
For researchers and
public health officials, though, the tests can reveal the true extent of the
pandemic. The U.S. National Institutes of Health announced April 10 that
researchers had begun recruiting people for a nationwide study that aims to test as many as 10,000 volunteers
without an official COVID-19 diagnosis, which could help clarify how many
people across the country have actually been infected. A number of similar,
more local studies are also under way.
The goal is to fill in
the gaps created by trouble rolling out diagnostic tests, which detect the
virus’s genetic material and can catch an active infection. Those tests have
faced roadblocks such as flawed tests and supply shortages, leaving some sick people
wondering whether their symptoms were from COVID-19 or a different respiratory
Such tests can’t detect
the virus once the infection has cleared. But antibodies typically stick around
in the body after the virus has disappeared, giving scientists a glimpse into
the past. So for people who weren’t
able to get a diagnostic test, the antibody test “will give us the ability to
let them know yes, you did have COVID-19,” says Aneesh Mehta, an infectious
disease physician at Emory University in Atlanta.
Knowing how many people
have already been exposed to the virus is also a step toward understanding when the pandemic might end (SN:
3/24/20). High numbers of immune people can protect the population as a
whole from outbreaks, creating what’s called herd immunity. Researchers
estimate that around one-third to two-thirds of a population would need to be
infected with SARS-CoV-2 to reach herd immunity.
Positive or negative
For an individual, an antibody
test result isn’t black and white: exposed or not exposed, immune or not immune.
This is in part because
antibody tests are not 100 percent accurate, says Angela Rasmussen, a
virologist at Columbia University. “They don’t accurately detect every single
antibody, and they may have both false positives and false negatives.”
In the tests, a small sample
of a patient’s blood is taken and exposed to proteins that match parts of the
virus. If any antibodies specific to the coronavirus are present, they should
recognize and bind to the virus components. Such antibodies might attach to any of a variety of places on the virus — including spots that are similar among closely-related viruses. As a result, researchers have to carefully
choose which part of the new coronavirus to use.
The tests usually detect
two types of antibodies. One, called IgM, is typically produced about a week after
infection and could identify patients who may still be infected.Levels of IgM begin to wane as the
body makes another type of antibody
called IgG, which can persist for longer periods of time.
The best antibody tests
are both highly sensitive — detecting a wide range of IgM or IgG antibodies that
recognize different parts of a viral protein — and highly specific, meaning the
detected antibodies are for only that virus. Coronaviruses that cause colds,
for example, also circulate around the globe. Antibody tests with low
specificity and high sensitivity might detect antibodies against cold viruses
and give a false positive. But a test with high specificity and low sensitivity
could miss antibodies, resulting in a false negative. Timing is also crucial,
as patients who have not been infected long enough to develop antibodies would
antibody tests have flooded the market, the U.S. Food and Drug Administration
has so far authorized just eight for emergency use. Based on data the tests’ developers provided to
the FDA, the sensitivity and specificity of the tests vary widely, from 88 to
100 percent for sensitivity and 90 to 100 percent for specificity.
In addition, “certain
people just don’t make as much antibody as other people do and don’t respond
the same to an infection,” Mehta says. “There will be some people that had the
infection, but we won’t be able to detect them.”
Immune or not
Even if the tests are
accurate, immunity is not a given. The tests being rolled out now look only for
the presence or absence of antibodies, not how effective those particular
antibodies are at knocking out the virus. And like antibody levels, that can
vary from person to person.
“We need to look at
people who do have antibody — and that does seem to be the majority of
patients — and see if that antibody is protective,” Rasmussen says.
In one cluster of
COVID-19 patients from China, most people produced high levels of neutralizing antibodies that prevent the virus from infecting new cells,
according to a preliminary report posted April 6 at medRxiv.org before peer
review. Of 175 patients with mild symptoms, about 70 percent developed
antibodies around 10 days after symptoms began. Among those, elderly and
middle-aged people had the highest levels.
Younger patients tended
to have lower levels overall, including 10 people who didn’t have any
detectable antibodies. But it’s possible that those 10 people developed antibodies
that recognized a different viral protein than the one used in the test, producing
a false negative result. It could also mean that a different arm of the immune
one that targets infected cells and doesn’t leave behind antibodies — may play
a heavy hand in recovery.
If researchers find particularly effective antibodies, they could be
used to develop treatments, such as producing lab-made antibodies or giving plasma from
recovered patients to those that are sick (SN:
It’s unclear what antibody levels provide the best defense.
“It’s very hard to protect the nose from being reinfected,” says Mark Slifka, a viral immunologist at Oregon
Health and Science University in Portland. People with lower antibody levels
could be more at risk for reinfection, he says, “but you might also be able to
still ramp up a rapid [immune] response” and prevent the virus from spreading
deeper into the lungs.
But even people with protective
antibodies aren’t necessarily “bulletproof,” Slifka says. Some people
may be completely protected against infection, a state known as sterilizing
immunity, which is hard to achieve. Others may get infected again, but have
mild or no symptoms.
Anecdotal reports from South Korea and China of patients who tested
positive after recovering have suggested that some people could be reinfected. But
nasal and throat swabs from 12 of these “reinfected” COVID-19 patients had no infectious
despite testing positive for the virus’s genetic material, officials from the
Korea Centers for Disease Control and Prevention said in a news briefing on
April 23. It’s possible the diagnostic test is detecting lingering fragments of
the coronavirus as it is cleared from the body rather than a reinfection.
When four rhesus macaques were infected, allowed to recover and then exposed to
the virus again, they weren’t reinfected, according to preliminary findings posted
March 14 at bioRxiv.org. That hints that at least in the short term, people may
be protected. To know for sure, “we would have to follow recovered COVID-19
patients who are antibody-positive for a long period of time and see if any of
them become infected again,” Rasmussen says.
Researchers also don’t know how long SARS-CoV-2 antibodies stick
around. Some viruses, such as measles, can trigger protection that lasts a lifetime. Defenses
against other viruses can wane over time. Studies suggest that protection against
cause the cold can last for about a year. Antibodies for the original SARS virus,
on the other hand, slowly vanished over a few years.
Since SARS no longer infects people, it’s unclear whether a lack of antibodies
means lack of protection. And because the new coronavirus has been infecting people
for only a few months, it’s still unknown whether it will behave similarly.
Despite the unknowns surrounding antibodies and SARS-CoV-2, some
countries including the United States are considering using antibody tests as a
stepping stone to provide so-called “immunity certificates” to people who test
positive that would allow them to reenter society or return to work. Some
experts, however, are skeptical.
“We don’t know that having antibodies necessarily means you’re
immune, so it could give people a false sense of security about how safe they
are,” Rasmussen says.
And, according to the WHO, that could increase the risks that the
virus will continue to spread.