When the first case of community-acquired coronavirus was discovered in Oregon, infectious disease labs across the state started developing tests to identify people sick with coronavirus. When it became clear that only a limited number of tests would be provided by the federal government, the need became even more urgent.

While they were working on testing, a team in the genomics lab at Providence Health Care Services in Oregon also started developing one that could identify people who had gotten sick and then recovered: an antibody test, also called a serology test.

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Dr. Carlo Bifulco, a pathologist and the medical director at Providence’s genomics lab, says they knew they’d need one eventually.

“We don’t know how many people have been infected with coronavirus,” Bifulco says, “and that number is very important for public health reasons.”

Related: Antibody Testing Is Coming To Oregon's Coronavirus Front Lines, With Big Caveats

Antibody testing can answer public health researchers’ questions about the new coronavirus. It can help estimate how many people in a population have been infected, and it can help figure out how many cases were asymptomatic or went undiagnosed. Getting a good estimate of the total number of COVID-19 cases is vital for epidemiologists and disease modelers who are trying to figure out how many total cases different areas might see, and how much they need to prepare.

It can also be important for healthcare workers, who may have been infected, and would like to know if they might be immune. And beyond the health care system, it could allow people who get tested to know if they have immunity and can return to work and school. But before we hand out "immunity passports," there's more we need to know.

Two weeks ago, Providence’s test was nearly ready. But they needed a way to roll it out. The oncology lab at Providence studies the ways cancer cells avoid our immune systems, and thought serology tests could be a way to learn more about how immune systems are responding to COVID-19.

“If we can identify health care workers who have been exposed to the virus in the past, we can learn a lot about what an immune response looks like,” says Dr. Rom Leidner, a Providence oncologist.  From there, it could also help them back-engineer a coronavirus vaccine.

Leidner proposed a study: to conduct a massive, voluntary serology survey of healthcare workers at Providence. His team worked around-the-clock with Bifulco to design the study, which would survey as many healthcare workers as possible every two weeks, and try to identify people who had been infected and developed an immune response.

By testing the same people repeatedly, they hoped to watch how immunity progressed, and how long it lasted: two big unanswered questions about SARS-CoV-2, the virus that causes COVID-19.

Negative tests have value too: if people tested negative and later tested positive, it could help them learn how fast the virus was spreading, and track mild or asymptomatic cases.

In just one week, they had their study up-and-running. It was nonstop work. Normally, it would take months to put everything together for a study like this one.

“These are extraordinary times,” Leidner said. “We don’t have the ability to do this in a methodical way like we usually would. We’d never execute it.”

And while other antibody studies are currently taking place, Leidner and Bifulco think this is the first study to test workers regularly over a long period of time.

“Writing up the study design, getting institutional approval, figuring out how to communicate in a secure and encrypted fashion. It’s been inspiring to see everyone signing up and working non-stop to make this happen,” Leidner said.

Before they’d even put out a press release, the response from healthcare workers was enormous.

“We had over a thousand people sign up in the first 48 hours, just by word of mouth,” Leidner said. By the end of the week, they’d tested over 1,700 people, and that number is still climbing. They’ve already expanded their study to a second Providence hospital in the area, and plan to expand to the entire Providence network, which operates hospitals in seven states. Eventually, they hope to collaborate with other healthcare providers.

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"With a kind of broad survey like this, we'll also be able to identify people who are immune," Leidner said. Not only would that inform decisions about the deployment of individual health care workers and limited supplies of personal protective equipment, doctors might be able to use the blood drawn from people with immunity to treat very sick patients, with what's called "serum therapy."

Serum is the part of your blood that includes important hormones, electrolytes, and, most importantly, antibodies. There’s some evidence that giving sick patients serum from recovered patients might give their body a boost to fight coronavirus.

Unanswered questions

There are some big questions about the coronavirus that still need to be answered before serology tests can be used on the general public, and to figure out who is immune and who isn’t.

The biggest, and most pressing question: can people who get infected with the new coronavirus get it a second time?

The World Health Organization says that's currently not clear. There are hundreds of credible, documented cases of people who appeared to have recovered from the coronavirus, and later got sick again. South Korean researchers who identified 140 such cases say it's unlikely these people were re-infected. They think it's more likely that the virus never really left their body and came back, or that the tests that indicated they'd recovered were actually false-negatives -- they actually had COVID-19 but the tests failed to detect it. Still, the possibility of re-infection can't be ruled out.

Most of the time when you get sick, your body has two responses. First, your innate immune system responds.That causes things like fever and body aches. It produces cells that move around your body eating any bacteria or virus they encounter.

Then your adaptive immune system responds. It takes about a week to ramp up. It’s able to identify different viruses and to produce antibodies, which flag germs to be destroyed. It’s your adaptive immune response that responds when you get a vaccine and become immune to whatever you’ve been vaccinated against.

Most infections trigger your adaptive immune system. But some don't. A study of recovered coronavirus patients in China looked at their blood serum. They found that some people had a strong immune response to COVID-19, while others didn't have much of one at all.

“It’s possible that they had such a strong [innate] response that they never had an adaptive immune response,” said Bifulco. In that case, they might not become immune, and also might not show up on antibody tests. It’s important to note this study has not undergone peer review by  other scientists, who would look for flaws in the study design.

Even if everyone infected with the coronavirus develops immunity, there’s no guarantee they’ll be immune forever. Generally, after an infection like that, you’re immune for at least a year, and immunity wanes as time progresses. At the end of that year, you might get sick again, but might not get as sick. Sometimes the virus or bacteria will mutate so quickly you can get infected again, and your immune system might not do a good job of attacking the new disease. That’s why you need a flu vaccine yearly -- to account for different strains of evolving virus that could be circulating.

By testing people who are currently healthy and continuing to test them, Bifulco and Leidner hope their study will help figure out just how strong the human immune response to the novel coronavirus is, and how many people have one at all.

Vaccinating for COVID-19

The work Leidner’s team is doing could produce results beyond antibody testing to identify immunity to the new coronavirus. They’re also among the dozens or organizations  across the globe working on potential vaccines for COVID-19 being developed. There are more than 60 in the works, according to the World Health Organization, and several have already started human trials..

Leidner says his background as a cancer researcher has left him well-equipped to work on a new coronavirus vaccine.

“For decades, we’ve been working on a vaccine against cancer,” Leidner said. “The idea is that you can harness an immune system to recognize that cancer is something foreign, and train the immune system to destroy it.”

Cancer treatments have evolved around that idea. For decades, doctors tried to treat some tumors by infecting the tumor with bacteria. The immune system would recognize something was wrong and send cells to attack the cancer.

Since the 1970s, immunotherapy has been a crucial part of cancer research and treatment. Some immunotherapies work by targeting the immune system directly, by inhibiting the “checkpoints” that act as breaks on the immune system. Other types of immune therapies use cytokines, which are “messenger molecules” that help immune cells respond to infections.

And, finally, there are vaccines for cancer. The challenge in developing cancer vaccines, Leidner said, “is that cancer cells are more or less like your own cells, except they grow out of control. So your target is only slightly different.”

Leidner’s team is working on something called a DNA vaccine. Gene vaccines, made out of DNA and RNA are at the cutting-edge of vaccine technology. It’s so new that there’s never been one approved, so there’s no guarantee it’ll work. But researchers are excited: One big advantage of this type of vaccine is that it can be manufactured more quickly than traditional vaccines, once one that works has been found.

The vaccine being created by Providence-Oregon isn’t in trials yet. It hasn’t even been approved by the Food and Drug Administration. But Leiden says they’re already starting to produce it, so if they get FDA approval they’ll be ready to start sooner with their first phase of trials.

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