UA researchers working on tests to detect COVID-19 antibodies in people without symptoms

University of Arizona researchers have begun using a test that can detect the presence of the COVID-19 virus in a person who has no obvious symptoms and possibly determine whether someone was once infected with COVID-19.

The test will be limited to a small number of patients to start, but it could help answer important questions about the breadth of the virus and the possibility of reinfection. More importantly, researchers hope to use the research to advance a vaccine or treatment for COVID-19.

University researchers received their first sample for testing from a confirmed and recovering COVID-19 patient on Friday. After the first sample is tested, researchers said they will continue to fine tune the test.

The test measures the presence of antibodies in a patient's blood. Antibodies are proteins created by the immune system to fight infections and viruses. If a person has COVID-19 or has previously had it, their body would have produced unique antibodies in response that would still be present in the blood after the infection cleared.

By studying the antibodies present in a person's blood, the two lead researchers, UA immunologists Deepta Bhattacharya and Janko Nikolich, hope to answer questions such as what unique antibodies are important to fight the novel coronavirus, how much of the population already had it and recovered or showed no symptoms, and whether it's possible to get reinfected with the virus.

Antibodies are crucial in figuring out how to fight the virus, according to Bhattacharya and Nikolich, and could be used to develop a vaccine or therapeutic treatment against COVID-19.

"One of the goals of what Janko and I would like to do is from these patient samples figure out which specific antibodies are protective," Bhattacharya said. "Then that actually can be something that is therapeutically useful."

Those specific antibodies could then be mass produced, Bhattacharya said, and injected into patients who are currently fighting COVID-19 to help boost their immune response. It would also be turned into a vaccine to give people some protections against the virus.

Unlike current tests that measure the presence of the virus in nose or throat samples, a patient does not have to be showing symptoms in order to test positive for antibodies for the virus in their blood and does not have to be actively infected.

"We're hearing anecdotally about people who were asymptomatic or mildly symptomatic and you know, there's really not testing available yet for people who have no symptoms," Bhattacharya said. "Is it possible that a much larger fraction of our community has been exposed to and cleared the virus than any of us are aware of? And I think that's where these antibodies ... come in."

So far the state has nearly 800 confirmed cases of COVID-19, but Nikolich suspects the actual number of people who have been infected is much, much higher.

"All we're seeing really is just the tip of the iceberg," he said.

Because of limited resources and time, Nikolich said the UA's antibody testing will not be used to conduct widespread testing of the population to figure out who has and hasn't had the virus already. Instead, they will be coordinating with health care providers to select the best patients to test in order to have good data to analyze.

Researchers did not identify the patient from the first sample. Separately, Doug Couchman, a 53-year-old bridge player and tutor, told The Republic on Friday that he had given blood samples earlier that day to UA researchers to use in an antibody test.

Couchman publicly announced last week that he tested positive for coronavirus after playing in two Tucson bridge games earlier this month. He said he released the information in hopes of warning other players who had been exposed. An Arizona Republic report found that no health official appeared to have attempted to warn any of the 700 card players who may have been exposed.

"This obviously is not something I wanted to, like, get famous for," he told The Republic. "But here I'm in a position to help and I'm pleased that I've been able to."

How antibody testing works

To prepare an antibody test for COVID-19, researchers isolate specific parts of the genetic material from the novel coronavirus that correspond to the virus' outermost vulnerable layer. This is important because the outermost layer, or shell, of the virus is what antibodies respond to.

SOURCE: Republic reporting; illustration by Nicole Schaub

One example of the virus' structure that must be genetically isolated is the telltale spike on the outside of the virus that sticks out and allows the virus to bind to and infect host cells. This part is especially important because it is targeted by antibodies, which essentially bind to the spikes and then block them from infecting a cell.

Once researchers isolate specific parts of the virus' genetic code, or RNA, they inject it into other types of mammal cells to make those cells grow with the same structure, or outermost shell, as the novel coronavirus.

"As they grow, they'll start to produce the spike protein," Bhattacharya said. "You can basically trick the cells into making what you want."

Growing the cells can take about a week, he said.

The entire virus structure is known as an antigen, defined as a foreign substance that the immune system responds to. The lab-grown spike protein would have the same shape as the one on the novel coronavirus.

The lab-grown antigens are then put into a special plate that immobilizes and concentrates the antigens on the bottom of the plate.

SOURCE: Republic reporting; illustration by Nicole Schaub

Health care workers then take a sample of a patient's blood and isolate the parts of the blood that contain the blood's antibodies into a serum. If a patient has coronavirus antibodies, they would be found in the blood, along with the other antibodies.

The serum is added into the plate with antigens. If there are antibodies specific to the COVID-19 antigen in a patient's blood, they will stick to the COVID-19 antibodies.

In addition to the serum, researchers also add a "detector" antibody that will stick to any COVID-19 antibodies and alert researchers to the presence of any COVID-19 antibodies by causing a reaction that will turn the liquid blue.

If the liquid in the plate is blue, it means a patient has antibodies for the novel coronavirus in their blood and either contracted the virus without having symptoms or has already recovered from the disease.

The limits to antibody testing

Because each test requires labs to grow cells into the right structures for the COVID-19 virus, there's a limit to how many people the University of Arizona can test.

"The making of those spike proteins is laborious. It's not something you can easily scale up," Bhattacharya said.

Each week, Bhattacharya and Nikolich's teams can make enough of the novel coronavirus antigen to test roughly a dozen samples.

"We have to be really careful about what we actually test," Bhattacharya said. "So it's not like this is something that we're going to be able to do widespread across the Tucson population."

At most, he estimates they will be testing around a hundred or potentially several hundred people, with a focus on testing health care workers and first responders as well as a good mix of sick COVID-19 patients and people who are highly suspected to be asymptomatic carriers of the virus.

Using this information, he said the teams will analyze the data from those tests to figure out which antibodies might work for therapeutic treatments.

Another limit to antibody testing is that a person has to produce antibodies to the virus in order to test positive, and the body's production of antibodies in response to an infection can be delayed.

Usually, the body produces a good amount of antibodies within seven days of an infection, but Nikolich said he has seen non-peer-reviewed estimates in the scientific community that, in some cases, it can take six to 12 days for the body to mount a good immune response to the novel coronavirus. Some of the most critically ill people may not be mounting a good immune response or any antibodies at all.

"It seems that some people aren't switching to the mode of protective immunity the way that we're used to seeing," Nikolich said. "So we really want to understand that part. Why is the switch not flipping the way that it should? Why is that so much more often happening in older adults and in certain vulnerable people? And how can we fix that?"

Instead of producing antibodies, many people who are severely ill are getting stuck in a mode where their immune systems are solely responding by producing inflammation and fluid in areas like the lung, according to Nikolich. That can be just as deadly as the virus itself.

He is particularly interested in figuring out why older people seem to be more susceptible to the virus and hopes that people like this could be helped if they are injected with the right antibodies to fight the infection.

Once samples are collected, he and Bhattacharya estimate that results for the test would be ready the next day, making it a little slower to produce results than current tests.

If a test shows that someone has a strong level of COVID-19 antibodies in their blood, this does not mean the person would be cleared to go back to work and doesn't necessarily mean they are immune to the virus, Nikolich said.

"This isn't a clinically validated test," he said.

While one small-scale non-peer-reviewed study on monkeys showed that the monkeys could not be reinfected with the new coronavirus, Nickolich said a lot more research has to be done to determine whether humans can be reinfected with virus and whether a strong antibody response means that a person has built up immunity to the virus.

Bhattacharya said his and Nikolich's research teams have enough material to start their first stage of testing. The last step before they begin is to figure out exactly how much of the antigen is needed for each test to work effectively.

"These are routine things that we do for our regular experiments. So I don't anticipate this is going to take us more than a few days," he said.

Once he and Nikolich have data from the initial tests, Bhattacharya said it's hard to tell when they can draw conclusions for therapeutic purposes or whether they will need to conduct more testing to draw conclusions from the data. Still, he hopes this research can eventually be used in collaboration with companies to manufacture vaccines or treatments that can help people.

"It's horrible the situation we're in, but to be able to contribute in some meaningful way is really thrilling," he said.

ASU is also working on tests

Arizona State University also plans to develop a blood-based antibody test for the novel coronavirus, as well as for the other six strains of coronavirus known to infect humans. Those include two other severe strains of coronavirus that have emerged in humans in the past few decades, severe acute respiratory syndrome, or SARS, and Middle East respiratory syndrome, or MERS.

"This could help us design a vaccine and help us understand why some people have more severe reactions than others," said ASU Biodesign Institute executive director Joshua LaBaer.

By testing for all seven strains of human coronaviruses, the hope is also to come up with a concoction of antibodies that could work as a universal vaccine or as protection against all coronaviruses.

"This test would be useful for future coronaviruses as well," LaBaer said. "And could help us identify people who are asymptomatic."

The hope is that a test like this could be useful in the event of future outbreaks to help clamp down on any virus spread.

ASU's antibody test is still in very early stages, he said, and months away from human trials.

Republic reporter Rob O'Dell contributed.

Amanda Morris covers all things bioscience, which includes health care, technology, new research and the environment. Send her tips, story ideas, or dog memes at amorris@gannett.com and follow her on Twitter @amandamomorris for the latest bioscience updates.

Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.

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