Testing to see who has the Covid-19 coronavirus has become one of the most crucial elements of slowing the global pandemic. And it may also hold the key to a return to normal.

“Everyone staying home is just a very blunt measure. That’s what you say when you’ve got really nothing else,” Emily Gurley, an associate scientist at the Johns Hopkins Bloomberg School of Public Health, told NPR. “Being able to test folks is really the linchpin in getting beyond what we’re doing now.”

In particular, serological tests, also known as “immunity tests,” for antibodies to the virus could reveal the true extent of the pandemic and help scientists answer basic questions about Covid-19 and the virus that causes it, SARS-CoV-2: How many people have been infected with the virus? Who may have spread it without knowing it? Why do some people have mild illness while others become gravely ill? How deadly is the disease? What tactics are actually working to slow its spread?

Serological tests could also potentially allow people who have immunity to return to work. That could be a huge boost to front-line health workers who may have been exposed to the virus but are desperately needed back in action.

Countries are now racing to acquire more of these tests. The United Kingdom ordered 3.5 million serological tests. Germany is considering using these tests to issue immunity certificates to people who have survived Covid-19.

In the US, the Food and Drug Administration on April 2 granted first approval to a serological test for Covid-19, with an Emergency Use Authorization. The test, made by Cellex, can generate results in as little as 15 minutes. Other companies and labs are jostling to develop serological tests in the US as well.

But scientists are also still learning how long immunity from Covid-19 can last and whether there is a chance that people could be reinfected. Filling in these blanks will be critical to the recovery from the Covid-19 pandemic. Let’s walk through what we know.

Serological tests can reveal who has defeated Covid-19 and may now be immune

In patients who have recovered from Covid-19 or may have carried the virus without realizing it, a serological test can show who carries antibodies, even if the virus is no longer present. Antibodies are proteins that help the immune system identify and eliminate threats. Once they’re made, they help the body neutralize future infections from the same threat.

Establishing who is immune is important for figuring out who can safely return to work. For example, health workers are facing staffing shortages as Covid-19 spreads through their ranks, and serological tests may soon become necessary to keep hospitals and clinics running.

These tests are also a forensic tool, tracing the spread of the virus through a population. This can solve some of the unknowns of the Covid-19 outbreak and help scientists get ahead of the next pandemic. Countries like China and Singapore have already used serological tests for contact tracing to see how the virus has spread.

Serological tests use blood serum, the liquid part of blood, excluding cells and clotting proteins. Even though SARS-CoV-2 isn’t typically present in blood, an infection causes white blood cells to make antibody proteins that help the immune system identify viruses and stop them, or mark infected cells for destruction.

Although these proteins can be detected in the bloodstream and blood serum, it can take several days for someone to make these antibodies after an infection. So a serological test isn’t always useful for finding an active infection — and can yield a false negative, showing that someone doesn’t have the virus when they actually do. The results of these tests can also be trickier to interpret than results from the more common RT-PCR tests used to diagnose Covid-19, which detect the virus’s genetic material.

But antibodies can linger long after an infection has faded. That’s why serological tests for antibodies can identify past cases of the virus.

“That’s a great screening tool to figure out what proportion of our patient population had it or what proportion of our hospital staff has been exposed to it,” said David Pride, associate director of microbiology at the University of California San Diego.

Researchers are also studying how to use antibodies collected from previously infected patients to treat current cases of Covid-19. The Food and Drug Administration (FDA) is now allowing doctors to use blood plasma from recovered patients that contains antibodies to treat emergency cases of the disease, and serological tests can identify potential antibody donors. (Potential donors can sign up here.)

Serological tests are also cheaper to run than RT-PCR. An RT-PCR test costs about $50 at Medicare rates. A serological test can be less than $10.

It’s faster, too, using techniques like ELISA (enzyme-linked immunosorbent assay). Here, a tiny piece of the virus is stuck to a plate. If an antibody to the virus is present in a blood sample, it will attach to the virus on the plate. Then a second antibody with an enzyme attached will stick to the virus antibody. The enzyme then accelerates a reaction that changes the color of the solution, indicating that the patient has at some point mounted an immune response to the virus.

There are other serological testing systems in development as well, including a fingerstick test that can deliver results in as few as 10 minutes. Meanwhile, RT-PCR tests can take several hours to run, and if samples have to be shipped to an outside lab, it can take days to get results. (The FDA recently approved a new rapid genetic test that can give a positive result in five minutes.)

A researcher works in a lab that is developing testing for Covid-19 in Nutley, New Jersey, on February 28, 2020.
Kena Betancur/Getty Images

However, as with RT-PCR tests, serological tests are also facing supply shortages and bottlenecks. And right now, the main task for combating the Covid-19 outbreak is figuring out who currently has the virus, which makes RT-PCR tests the priority. But as the US heads deeper into the pandemic, serological tests will become essential to finding a path out.

Researchers still aren’t sure how long Covid-19 immunity will last

If serological tests are deployed even more broadly, health officials can trace the spread of the illness. Coupled with widespread RT-PCR tests to find active cases of Covid-19, scientists could identify hot spots, and governments can more precisely target their tactics. Rather than blanket shelter-in-place orders, officials could see which cities, neighborhoods, and people are most at risk and start to relax quarantines, curfews, and other control measures in some areas.

Widespread testing alongside social distancing can slow the spread of the virus and eventually help restart idled economies and bring countries closer to where they were before the pandemic.

But there are some caveats.

To safely return to work, a patient would have to ensure that they have immunity and that they are no longer spreading the virus. Since a serological test can only confirm the former, a patient may still need an additional RT-PCR test to establish the latter. That is, they need to test positive for immunity and negative for the virus itself.

SARS-CoV-2 is also a new virus, so researchers aren’t certain how long immunity will last. The virus could mutate and render past immunity ineffective, although scientists have found that it is mutating slowly, indicating that the protection from a past infection is likely to be effective for a while.

“You’re going to have some degree of durable immunity,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told the Doctor Mike YouTube show. “It may not be 50 years, but it’s certainly going to be a matter of a few years.”

Resolving these questions about immunity is essential to determining whether it’s safe to go back to work, particularly in health care. “We need to check to make sure the protection is real before doing that on a large scale, but I do think [serological testing] will be an important part of the strategy because we’ll need to keep health care workers in action,” said Marc Lipsitch, a professor of epidemiology at Harvard University.

The possibility of protection from the pandemic — and a test to show it — should also not be an incentive to try to get infected in the hope of building immunity. Covid-19 is a dangerous illness. While older people are generally most at risk, people of all ages have become seriously ill and have died from it. Infected people can also spread the virus to others more at risk, even if the infected person has no symptoms.

And there are still not nearly enough materials for either widespread RT-PCR or serological testing. There are also critical shortages in protective equipment for medical staff conducting these tests. That’s making hospitals and clinics think carefully about who needs to be tested right now and moving serological tests for people who aren’t sick anymore to the back burner.

Getting the amount of testing needed to end the pandemic is also no trivial task. It would demand an extraordinary coordinated effort of not just deploying tests but training a workforce to do them. In addition, people would have to maintain strict social distancing measures until all the requisite testing is completed, which could take months. “It would take a sort of moonshot-level effort,” wrote Vox’s Brian Resnick.

As manufacturers ramp up production to meet the surging testing demand, these supply shortfalls will likely fade. But in the meantime, some difficult decisions lie ahead.

“In the US, we’re not accustomed to being in a resource-limited environment, but when it comes to testing for Covid, we still are in a resource-limited environment,” Pride said.

Ultimately, the threat will fade when enough people are immune to the virus that it can no longer spread easily, or if pockets of Covid-19 are contained until they burn out. Getting immunity from exposure is a costly and dangerous approach, so the best strategy remains not getting infected in the first place and buying time until researchers can develop and deploy a vaccine. And in the meantime, test, test, test.

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