By Katie Kerwin McCrimmon and Lindsey Reznicek
A team of scientists at the Anschutz Medical Campus is racing to create a new, high-quality antibody test that could be scaled to provide plenty of tests to people throughout Colorado in the coming months.
Antibody Testing – Frequently asked questions
What are antibodies?
When we get infections, our bodies create proteins to fight infections. These are called antibodies.
What’s the difference between an antibody test and a test for COVID-19?
A test for COVID-19 detects the presence of the virus itself whereas an antibody test detects antibodies to the virus. Antibody tests can show that a person had an infection in the past. But, it’s possible for people who still test positive to COVID-19 through a viral test to also test positive for antibodies. Medical providers should not use antibody tests to determine if a person has COVID-19. And, some commercial antibody tests have been inaccurate.
How long does it take for a person to create antibodies?
It can take days or weeks for a person to develop antibodies.
Do antibody tests for COVID-19 work?
Many commercial antibody tests do not work well, and therefore can be concerning. That’s because people could assume that positive antibody test results mean they are immune to COVID-19.
Medical experts don’t know yet if antibodies to COVID-19 will protect people from future infections. Researchers are working to learn if antibodies will be protective, and if they are, how long they would last or how many antibodies would be necessary to fight COVID-19. In addition, the virus can change or mutate as it travels from person to person and country to country. That’s what happens with the flu virus. And that’s why we need a new flu vaccine every fall. The virus has changed, and therefore, the flu vaccine must change as well.
Is UCHealth offering antibody testing?
No. Not yet. Experts at UCHealth are working to validate commercial tests to determine if they are accurate. In addition, researchers and lab scientists at the Anschutz Medical Campus are working to create an accurate, high-quality, homegrown antibody test for COVID-19. This test is not ready yet, but could be available within weeks or months.
Why is it so hard to create an accurate, high-quality antibody test?
COVID-19 is an infection that stems from a type of virus called a coronavirus. Coronaviruses are very common. Some of them cause common illnesses like the common cold. But, the specific coronavirus that causes COVID-19, SARS-CoV-2, is highly infectious and can be dangerous or deadly. Some inaccurate antibody tests are resulting in what are known as “false positives.” These tests may be detecting other coronaviruses, but not SARS-CoV-2. Be very cautious about results from an antibody test.
Does a positive result from an antibody test mean a person is immune to COVID-19?
Even if a test is accurate, medical experts don’t know yet if antibodies for COVID-19 will prevent future infections. More research is needed into the virus that causes COVID-19, antibodies, and possible immunity.
Should I buy an antibody test at a pharmacy and count on its results?
No. You should be very cautious about antibody testing. Work with your doctor if you think you need antibody testing.
If I have a positive result from an antibody test, am I immune? Will I be protected from getting COVID-19 in the future?
Until antibody testing and immunities related to COVID-19 are much better understood, you should continue to follow all recommended precautions to avoid catching or spreading COVID-19, even if you think you have had COVID-19 in the past or even if you’ve gotten a positive result to an antibody test.
Wash your hands regularly. Keep at least 6 feet away from people in public. And, if you are sick, stay home. If you need medical advice, please consult with your provider. If you are concerned about going out for a doctor’s visit, you can easily do a Virtual Visit.
Many challenges have slowed the development of antibody tests for COVID-19 in the U.S. After tightly controlling testing for COVID-19, the U.S. Food and Drug Administration relaxed requirements for antibody testing. That has led to some questionable tests, which have yielded inaccurate results. In addition, shortages in raw materials have slowed the development of antibody tests.
To bypass these problems, researchers and scientists at Anschutz are growing their own ingredients. That will allow them to guarantee that they’ll have enough raw materials to create the tests, while also assuring that the tests are accurate.
You could think of this team as gourmet chefs who are making an antibody test from scratch.
“This is farm to table testing,” said Dr. Brian Harry, medical director of special chemistry at UCHealth University of Colorado Hospital and an associate professor of pathology at the University of Colorado School of Medicine.
“We have an on-campus garden,” Harry said.
But, rather than growing vegetables, this garden is producing viral proteins in a lab at the University of Colorado Cancer Center.
UCHealth’s CARE Innovation Center is funding the efforts to create the new test.
“We’ve been working very hard at building capacity to do antibody testing,” said Dr. Richard Zane, UCHealth’s Chief Innovation Officer and director of the Innovation Center.
In addition to the test that Anschutz scientists are creating, Zane said his team is working to validate one of the few commercially available tests that may be reliable.
“We are thinking very carefully about how to deploy antibody tests,” he said.
The Anschutz team has been keeping Colorado Gov. Jared Polis’ testing experts apprised of their progress and the governor’s policy experts are eager to have a new supply of high-quality antibody tests to deploy in Colorado.
“Antibody tests that measure the body’s response to COVID-19 will likely be an important tool to understand where the virus has been, how it has spread and how effective our transmission-reduction strategies have been,” said Sarah Tuneberg, director of Colorado’s Innovation Response Team.
“We’re excited about the promising work the team at UCHealth has undertaken,” she said. “Once complete, their new ELISA (enzyme-linked immunosorbent assay) platform will set the standard for antibody tests that are more accurate and less dependent on commercial supply chains.”
New, more reliable antibody tests coming soon to Colorado
Antibodies are the proteins that the body makes to fight invaders like the new coronavirus. Antibody tests for COVID-19 aim to detect antibodies that the body creates in response to the infection. (Click here to learn more about viruses.)
Antibody tests could be valuable both for researchers who are trying to understand the percentage of people who have been infected with the new coronavirus and policy makers who are trying to reopen economies while keeping people safe.
In addition, since there are no cures and no vaccine yet for COVID-19, medical providers are using transfusions of plasma from people who have recovered from COVID-19 to help those who are critically ill. People who think they had COVID-19, but never were able to get tested may be able to get antibody testing in the future to determine if they can donate what’s known as convalescent plasma. (Click here to learn more about the first patient who received convalescent plasma in Colorado. And, click here to learn more about donating plasma.)
The team creating Colorado’s homegrown antibody test is on track to have tests ready by mid-May. The first tests likely will go to health workers. The team will keep refining their recipes to boost the quality of the antibody testing in the coming months. And, ultimately, the Anschutz researchers hope to scale their production of the tests so they can provide enough antibody tests to support Colorado’s efforts to fight the pandemic.
Antibody testing challenging because inaccurate tests can incorrectly flag other viruses
For now, UCHealth isn’t offering antibody tests to members of the public for a variety of reasons.
“Even if you have been exposed to COVID-19, that doesn’t tell you that you have immunity or how long it will last,” Zane said.
The other problem with antibody testing stems from the poor quality.
One group of researchers tested 14 commercial tests and found that only three were reliable. Even the best tests had problems, researchers found.
Many of the commercial antibody tests have produced “false positives,” indicating that a person has antibodies to the new coronavirus, SARS-CoV-2, when they actually have antibodies to something else, such as coronaviruses that cause the common cold.
High quality antibody tests must have both high sensitivity and specificity. They must be sensitive enough to detect antibodies, but they also must be “specific” enough to detect the new coronavirus that matters now. Many of the antibody tests that were rushed to market have a higher probability of being wrong than right, at least at this point in the pandemic.
“To the layperson, a specificity of 92% may sound really good, but it’s actually horrible,” Zane said.
He urged people to be extremely cautious about running to the drug store and getting any antibody test they find. He urged people to work closely with their doctors.
“You may be able to walk into a pharmacy and get your own test or even go to a local clinic offering antibody testing, but most are not FDA approved and are not good enough to make any medical decisions,” Zane said.
So-called ‘Immunity passports’ unlikely any time soon
“Antibody tests may be valuable in providing an epidemiological perspective,” he said. “What worries me is that people will feel they have won the lottery: ‘I have antibodies. I’m safe. I’m protected.’”
But researchers don’t yet know whether a positive result to an antibody test means that a person will be immune from COVID-19 in the future. Many infectious disease experts worry that positive antibody tests will give people a false sense of security.
If people believe they are immune to COVID-19 when they are not, they could get sick or infect others.
“It has to be a good test. If not, it’s beyond worthless,” Zane said.
“Based on what we know about coronaviruses in general, there’s a high probability that someone who has had COVID could be infected again. If they get re-infected, we don’t know if it would be more mild or nonexistent. Having antibodies may provide some level of immunity. But, we don’t know how long it will last, and if the virus changes, to what degree the antibodies will work,” he said.
“The concept of an ‘immunity passport’ could be very dangerous,” Zane said.
Despite the uncertainties about how protective antibodies will be, Harry and his colleagues believe it’s important to have high quality antibody tests in quantities which would allow broad use.
That’s why leaders at the Anschutz Medical Campus and UCHealth’s CARE Innovation Center are investing in the effort to create tests from scratch.
“Although it remains unclear if antibody testing will have a role in caring for individual patients, it is an important tool to help epidemiologists detect and describe the way the virus is spreading, and that alone more than warrants the investment,” Zane said.
Homegrown antibody tests will provide affordable, renewable supply of antibody tests
Dr. Harry said the system that the Anschutz team is using is appealing because it’s relatively inexpensive. And, if everything works properly, the team can easily scale their system to produce plenty of tests to support Colorado health systems and community leaders.
“This is a cost effective approach,” Harry said. “You’re not paying someone to do all of these independent steps for you. It’s similar to cooking at home. You have the recipe. You have all the ingredients and you put it all together.”
Getting fancy food at a restaurant or even a meal kit delivered to your door is much more expensive than buying your own ingredients and cooking from scratch.
The same is true in creating antibody test kits, Harry said.
“In this case, you’re building or buying all the ingredients yourself,” he said.
The key ingredient that the team needed first was a viral protein. That’s where Thomas “Tem” Morrison stepped up. Morrison is an associate professor of immunology and microbiology at the University of Colorado School of Medicine.
Antibodies do their work by attaching themselves to proteins. In order to create a test that can find antibodies in a person’s blood, the Anschutz team needed plenty of proteins to attract antibodies.
“The supply chain for laboratory reagents (substances that trigger chemical reactions) has been unreliable and unstable. So, in order to make sure we had access to testing that we could offer in the long term and reliably to patients, we needed viral proteins for the antibodies to bind to,” Harry said.
Making antibody tests from scratch starts with homegrown viral proteins
To start the process, Morrison had to pick a good viral protein.
“It’s the key ingredient for any test looking for COVID antibodies. Antibodies are the proteins that our body makes to help provide protection from an outside source. Those antibodies should bind to the virus,” Harry said.
The quality of the protein will affect the quality of the test.
“The key thing is choosing the protein,” Harry said.
Morrison is a virologist and helped the team focus on what’s known as a “spike protein.”
That was step 1. Step 2 was growing the protein so the team would have plenty of proteins to create plenty of antibody tests.
Morrison started growing the proteins in a lab at the University of Colorado Cancer Center.
“When you grow proteins, you use genetic instructions to grow the proteins in cells. Morrison is an expert virologist who has been a key part of of this team, in part by providing those instructions in the form of plasmids,” Harry said.
The lab technicians who tend the cells add plasmids to help the cells grow. That’s the gardening part of creating the antibody tests.
The next part is figuring out how to carry out the testing. To do that, the team is using what’s called an ELISA assay.
ELISA stands for enzyme-linked immunosorbent assay. It’s a type of test that can measure antibodies, antigens and proteins in biological samples. These tests are common. They’re used to determine if a woman is pregnant or a person has HIV. If the test is positive, the color in the sample changes. Click here to see an animation showing how ELISA assays work.
The art of creating antibody tests: Colorado team tapping FDA-approved assay from Mt. Sinai
While the tests are common, there’s an art to creating them well. To move the process along faster in Colorado, the team is using an assay that a team at Mt. Sinai created. The Mount Sinai assay has already received emergency use authorization from the FDA.
“The fact that it has been executed and approved gives us a high degree of confidence that it will work here as well,” Harry said. “There’s a lot of nuance that contributes to the power of the assay.”
Harry and Morrison have been working with Dr. Edward Ashwood, a professor and vice chair for clinical pathology, Dr. Dara Aisner, an associate professor of pathology and laboratory medicine and Dr. Ashley Frazer-Abel, an assistant professor who has a lab on the Anschutz campus where she will evaluate how well the tests are working.
Frazer-Abel’s lab meets the highest standards for clinical lab testing. It is certified by the federal government under the Clinical Laboratory Improvement Amendments of 1988, known as CLIA. And the lab is accredited by the College of American Pathologists or CAP.
One of the problems with some commercial antibody tests is that they may reveal a positive result even though a patient has not previously had COVID-19, so-called false-positives.
“The big issue is specificity, developing and optimizing tests so we have the ability to tell if someone is a true positive,” Harry said. “That would indeed mean that they have had the viral infection before.
“As we try to make these important decisions about social interactions, one of the biggest risks is a false positive. The risk of that is especially high right now given that the percentage of people who have had COVID-19 in various studies appears low,” Harry said.
After creating the test, scientists will refine it, then ramp up production fast
Early research is showing that fewer than 5% of people have been infected with the new coronavirus, although we still don’t know much about the state of Colorado.
“The bottom line is that most people probably haven’t had the infection yet,” Harry said.
The high risk of infection means the accuracy of the testing is especially important.
Once the team has a good system in place, they can do a lot of tests.
“We can perform thousands of tests using our homegrown operation,” Harry said. “The longer term plan would be to scale our operation significantly as needed in coordination with local public health authorities.”
While world leaders, U.S. governors and health systems around the world are competing with one another to get supplies like masks, cotton swabs and commercial reagents, Harry said the homegrown antibody tests are very appealing because the team can keep resupplying themselves.
“It’s highly sustainable. You can grow your own proteins. They are not a limited resource,” Harry said. “We envision these tests as being extremely important.”
Assuming that high quality antibody testing becomes available, Harry said the tests — in combination with adequate testing to determine if people currently have COVID-19 — can help boost safety.
“The goal is to make sure leaders in Colorado know that we can create access to high quality testing,” Harry said.
The Anschutz team is briefing Gov. Jared Polis’ testing task force, known as the Mass Testing and Innovation Response Team.
The test could be ready for members of the public in weeks. In the meantime, Harry said UCHealth labs are working to get adequate supplies of the most accurate commercial antibody tests.
“We want to help our patients and serve our health care workers,” Harry said. “We could supply lots and lots of tests by using this assay and available commercial platforms.”
Other countries with more centralized forms of government have used testing much more aggressively than the U.S. In the U.S. each state is taking its own approach.
Harry said the Anschutz team has worked quickly thanks to a network of people with varied and valuable expertise.
“This is a very unique collaboration,” Harry said.
While the first goal is to create a highly accurate test, the second step will be to keep refining it. In the future, the team is considering conducting “side-by-side” testing. The team could explore using two different viral proteins. With one blood draw, a test subject’s blood could go into two, side by side tests to help reduce the chances of false positive results.
For now, the first job is to keep “farming” proteins.
“We’re calling this the homegrown ELISA,” Harry said. “It’s very exciting … We want to meet the needs of our institution and our state.”
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