In the coronavirus pandemic, the next testing challenge will be to diagnose the recovered.
Identifying those who are no longer sick with COVID-19 may not seem as urgent as testing those who may be newly infected. So why scramble to confirm that patients have returned to health or find ones who never seemed sick in the first place?
The answer: Because they can provide care, and perhaps a cure, for those who are sick with COVID-19. And their numbers will offer a barometer of how near we are to this pandemic's end.
Public health authorities suspect that tens of thousands of Americans, if not more, have had COVID-19 without realizing it because they suffered few or very mild symptoms.
Around the world, more than 100,000 former patients have been tagged as "recovered." But that is likely a tiny fraction of the true total.
Now immune to reinfection _ at least for a while _ many of these recovered people could safely go back to work. They could care for those who are ill or who are at high risk of dying if they become ill. They could donate their antibody-rich blood to be used as medicine for the critically ill.
They could be among the first to return to life as we used to know it.
But first, officials need a test to identify this population.
With President Donald Trump holding out the imminent prospect of resuming our usual ways, health officials say that knowing who had already recovered, and what percentage of the population they represent, would be vital for a safe return to normal.
Understanding how many people were immune to the new coronavirus would help public health officials anticipate their communities' health care needs by assessing how many remain vulnerable and how aggressive the virus actually is.
"If we don't test," said microbiologist Esther Babady of Sloane Kettering Cancer Center, "then we don't know what's going on and we really don't know the extent of the virus."
After a disastrous rollout, tests capable of detecting an "acute infection" _ the presence of the SARS-CoV-19 virus actively replicating inside the body _ are finally starting to be put to broad use. Without those tests, health officials said they were flying blind as the pandemic spiraled.
The newly fielded diagnostic tests can't pick up a past infection with the coronavirus, however. And until officials can see how much of the U.S. epidemic has already passed, they remain partly blind.
Tests that can detect an infection after it has cleared are called "antibody assays." They measure the presence and population size of antibodies, the living record that the immune system keeps of viruses it has seen and beaten down.
Today, antibody assays for COVID-19 are available only in research labs. They have not yet been designed for widespread commercial use, tested for safety and accuracy, or cleared for deployment by the Food and Drug Administration. They have not been manufactured, nor have distribution plans for these nonexistent medical devices been drafted.
But the spadework for a COVID-19 antibody test is just beginning in microbiology labs across the country. It could be months _ as long as a year _ before the tests could be widely offered.
The scientific and practical hurdles that come with fielding an antibody assay are legion, and scientists worry that, as with the COVID-19 diagnostic tests, their efforts will come too late to help.
At a moment when reliable treatments for COVID-19 have not yet emerged, it's all the more essential to discern who remains vulnerable and who has gained at least temporary immunity, said immunologist Michael Schmidt of the Medical University of South Carolina.
"You could actually deploy certain fractions of the population back" into the workforce, he said.
In China, eight types of COVID-19 antibody testing kits have been approved for clinical use, the Xinhua News Agency reported last week.
In the United States, virologist Florian Krammer and his colleagues from the Icahn School of Medicine/Mount Sinai Medical Center in New York have published instructions for a COVID-19 antibody test that other labs could use to stand up their own testing capability. By following the step-by-step recipe, even labs without lavish resources could scale it up to test a few thousand people a day, the Mount Sinai team said.
That would be enough to gather blood from patients whose antibodies are strong and plentiful enough to make treatments using "convalescent plasma." Still under development, such therapy would use so-called neutralizing antibodies harvested from patients who have recovered from COVID-19 to treat or prevent COVID-19 illness in others.
The Mount Sinai test scans for antibodies in serum, the straw-colored fluid in which blood cells are suspended. To detect the antibodies, scientists created copies of the surface proteins found on the SARS-CoV-2 virus, which pair with the antibodies like a lock and key.
If that pairing is made, the test changes color to signal that the antibodies were found, said Daniel Stadlbauer, who helped create the test. A machine will discern in greater detail the concentration of antibodies a patient has generated in response to his infection.
Use of such a test beyond research would require clearance from the FDA. But once fielded, the test could identify recovered doctors, nurses and other medical specialists, as well as the legions of hospital workers who serve meals, clean operating rooms, manage equipment and transport patients. Such a workforce of recoverees could be dispatched to the front lines of caring for COVID-19 patients with little risk to themselves.
"Those are the most important people to test," Stadlbauer said.
Dr. Crystal Mackall, a Stanford physician who researches immunotherapies, called the rapid development of the antibody assay a "quite impressive" accomplishment. Similar tests for established viral infections are quite standard, she said, but it's not easy to ensure a test accurately detects the body's immune response to a wholly new virus, she said.
Time and experience will tell how reliable the test is. Only with broad use will scientists gain confidence that the lock cannot be "picked" by antibodies for other infectious diseases, such as other coronaviruses or influenza.
Stadlbauer said that scientists are not certain whether the presence of antibodies can overlap with an active COVID-19 infection, or only become evident after a patient has fully recovered. As a result, the ideal timing for testing a person isn't completely clear.
Finally, scientists are eager to learn how long COVID-19 antibodies will confer immunity to those who have them. Early evidence suggests COVID-19 cannot quickly be re-caught, and that antibodies to coronaviruses may last a good while.
The coronavirus that caused Middle East respiratory syndrome, or MERS, was still active in humans three years after they were infected.