How this new method of coronavirus testing could help Kentucky reopen its economy
When someone contracts COVID-19, the disease caused by the new coronavirus, their immune system should respond by pumping out antibodies to attack it.
For the majority of people, this natural defense mechanism works. When the live virus is shed, those antibodies continue living on, potentially creating some level of immunity, or increasing one’s ability to fight it off if it’s reintroduced.
Researchers in Lexington and Louisville are trying to capitalize on this biological response with a new, home-grown testing method they say could eventually provide unprecedented insight into a still elusive virus and the body’s response to it. Other hospitals are poised to follow suit with commercial tests, as more labs across the country clamor to get antibody tests online.
Among characteristics researchers hope to pinpoint is just how many people have mounted immunity to the virus — a metric no one really knows, yet — and what true immunity looks like, said Dr. Aruni Bhatnagar, a professor of medicine at the University of Louisville and director of the Christina Lee Brown Envirome Institute.
In Louisville, researchers also plan to use this test to locate plasma donors — people who developed a strong immunoresponse and recovered from the virus — to help treat patients with advanced COVID-19, Bhatnagar said. These experimental transfusions are also being practiced at some Lexington hospitals.
Though using antibodies as a viral detection tool is just one weapon in a global arsenal to fight the pandemic, this new method of testing could prove vital in determining the true reach of the virus, which often plants itself in one’s system without ever provoking symptoms, exaggerating the likelihood of spread. Testing in Kentucky right now is, for the most part, only reserved for the sickest patients, meaning large swaths of asymptomatic carriers have gone untested.
So far, more than 33,000 people in Kentucky have been tested for the live virus, and the state is still likely climbing toward its peak number of cases, though Gov. Andy Beshear has said there is evidence to suggest the state’s curve has started to plateau. Still, at least 3,192 people have been infected with COVID-19 and 171 have died.
If used correctly, antibody testing, combined with live virus testing, could equip state leaders with key data needed to begin assessing when and how quickly to start easing certain restrictions, researchers say, especially when it comes to resuming some medical procedures such as elective surgeries.
Deploying this method of testing will provide the “first steps toward understanding the prevalence of the disease, who has been exposed, and who has not,” said Dr. Dan Rodrigue, an infectious disease specialist in Lexington.
But Kentucky still has a ways to go. On Tuesday, Department for Public Health Commissioner Steven Stack said the state’s testing capacity is only a third or fourth of where it needs to be in order to hit the necessary threshold for reopening, outlined in seven benchmarks Beshear introduced last week.
“So, we’ve got to ramp it up quickly,” Stack said.
How it works
At the University of Kentucky, the COVID-19 Unified Research Experts (CURE) Alliance and their partners are likely days away from rolling out these quantitative antibody tests for clinical trials. A consortium of health care institutions in Louisville rolled out news of a similar test last week, with an aim of first testing thousands of frontline health care workers at three local hospitals, and then a few thousand Louisvillians.
Research labs at UK, modeling after a DNA sequence of the virus created at Mt. Sinai Hospital in New York City, manufactured their own genome sequence of COVID-19, and extracted the spiky viral proteins that are targeted by an immune system’s antibodies, said Dr. Becky Dutch, a UK virologist and biochemist who’s on the CURE team.
Researchers then mix these manufactured proteins into a blood sample as an antibody detection tool. If antibodies are present in the blood, it means that person’s immune system has already come into contact with the virus and mounted some sort of response to it. Researchers will eventually use real viral proteins extracted from positive patient’s blood samples.
“If you have antibodies in your blood, [their] job is to recognize those proteins” by latching onto and attempting to neutralize them, Dutch said. In a lab setting, using this test, “we can check whether that happens.”
Right now in Kentucky, the most common test for COVID-19 is a nasopharyngeal swab — when a 10-inch-long flexible stick is pushed far up the nose to collect a sample of mucus from the back of one’s nasal cavity.
This method helped diagnose the more than 3,100 Kentuckians who’ve been infected. More than 30 different labs are processing these tests, including in-house labs at U of L and UK, but only about .75 percent of the state population has been tested — a sliver of what will ultimately be needed to reintegrate society as it adapts to a “new normal,” Beshear has said.
While the state has adequate lab space and machines to accommodate testing on a much wider scale, current capacity is contingent on testing supplies and personal protective equipment needed for workers performing these tests — items that continue to be in chronic short supply, the governor has said repeatedly.
Antibody testing, overall, would likely require less PPE, since one milliliter of blood could be used for hundreds, even thousands of tests, said Dr. Vincent Venditto, an associate professor at the UK College of Pharmacy who’s in charge of one of the three labs at UK building an antibody test.
Tracking herd immunity
But an antibody test would not replace a nasal swab as a way of testing for the virus. Instead, since what each test reveals is slightly different, the two would work in concert, Venditto said.
A nasal swab shows whether someone currently has the live virus. Many health care professionals believe it takes 10 to 14 days after the virus is contracted before symptoms develop. This is the ideal time to perform a nasal swab — when the viral load is at its peak, Venditto said.
But a nasal swab only shows if a person has the virus in their nose, meaning the window of its usefulness is narrow, and even then, it’s not foolproof.
For example, if the virus has moved from a person’s nose into their lungs, a nasal swab result might return negative, despite the virus still being present.
What’s more, a nasal swab can’t be used for retroactive COVID-19 detection, but an antibody test can, making the two complementary, Venditto said. A nasal swab is intended to reveal a virus that’s live and contagious, while an antibody test more often illuminates the imprint left behind by a virus weeks, months, even potentially years after it’s gone.
An antibody test shows “evidence of infection, but not necessarily whether you are actively infected and shedding live virus,” Rodrigue said. “That’s an important feature to figuring out how to go forward: is your population more susceptible or less susceptible?”
It’s also known that “these antibodies do wane over time,” but when, exactly, is unclear, he said.
Not only could this type of combined testing provide a more complete picture of infection in the state, it could ensure greater protections for frontline health care workers and those they care for, by making it clearer who has built up immunity, and who is still at risk of catching and spreading it.
If researchers through mass testing are able to chart what percentage of Kentuckians have been exposed to the virus, they can track what’s called herd immunity — when a large swath of the population is protected against an infectious disease because most people have already caught it and built up antibodies to fend it off, decreasing the potential for future spread.
And, Dutch said, as Kentucky in the coming weeks begins gradually reopening some targeted areas of the economy, having a grasp even on spread within a specific population, such as health care workers, will prove crucial in ensuring that process happens without needlessly exposing those who may still be vulnerable.
“As we ask the questions about when to open things back up again, this matters,” she said.
‘Assurance these antibodies are effective’
The University of Louisville’s Center for Predictive Medicine is already a step ahead.
Last week, Beshear announced the launch of a long-term COVID-19 study, called the Co-Immunity Project. It’s a multi-phase collaboration between U of L and the Christina Lee Brown Envirome Institute, to first gauge the status of COVID-19 infection rates in frontline health care workers in Louisville, and then expanding it to randomized community testing, said Bhatnagar, one of the project’s lead researchers.
So far, Kentucky has largely stuck to the Centers for Disease Control and Prevention testing guidelines, limiting the available tests for only those with acute symptoms, including cough, shortness of breath and a fever. People over the age of 65, or those in long-term care facilities are also given priority. The Co-Immunity Project will be one of the first endeavors to test a large swath of asymptomatic people in the state.
Over the next few weeks, researchers will collect blood samples from as many as 6,000 frontline health care workers at U of L, Norton Healthcare and Baptist Health in Louisville. Starting in May, Bhatnagar and his team hope to collect these samples from a few thousand Louisvillians across demographics. For those with a strong immune response, their plasma may also be harvested to donate to patients with acute cases of COVID-19.
Bhatnagar said the goal is then to follow those participating frontline workers for a year, to see whether they get reinfected with COVID-19.
“If they don’t get reinfected, you would have reassurance that these antibodies [they produce] are effective,” he said. “Generally speaking, in most of the other flu viruses, and even [with] SARS,” which is another strain of coronavirus, “there is good indication that, once you get infected, you develop immunity.”
But since this strain is new, “so far, we know nothing” conclusive about it, said Bhatnagar, including the level and strength of antibodies needed to build up immunity: contracting it once might not necessarily prevent one from catching it again, in other words.
What he wants to figure out is, “if you see these antibodies in some people, would it impart them immunity?” Bhatnagar said, calling it “the most critical question” he’s hoping to answer.
‘Not a simple equation’
The timelines on both UK and U of L projects are still in flux — UK’s, for example, has not yet been granted final approval, and U of L hasn’t yet begun collecting blood samples — meaning counting it as a robust tool in the state’s current tool belt is still premature. It’s a point compounded by mounting pressure on Beshear to reopen the state’s economy.
This week, some of Kentucky’s neighbors to the south, including governors of Tennessee and Georgia, said they would fast track their respective state’s reopening starting May 1, even though there’s incomplete evidence that either state’s infection or death rates have waned.
Kentucky’s testing capacity is expanding at this point almost daily. The state recently acquired 15 rapid testing machines, for example, that will allow the medical community to process individual nasal swabs in a matter of minutes. Kroger is hosting pop-up testing at store locations across the state, including in Paducah, Madisonville, Somerset and Pikeville, with a goal of testing 20,000 people. And more hospitals are rolling out testing opportunities, including Hardin Memorial Health and Ephraim McDowell Health in Central Kentucky, and St. Claire HealthCare in Eastern Kentucky.
Still, ramping up testing is just one piece of a very complicated puzzle that needs completing.
“Reopening is not a simple equation of just testing. It’s testing, it’s PPE, it’s infrastructure, it’s people available in the public health sector to be able to help with quarantine, with contact tracing,” Rodrigue said. “It’s a difficult calculus, and something all organizations are trying to figure out.”
And the ideal testing scenario?
“Really it’s when the testing for the virus and antibodies is as commonly available as testing for a strep throat infection, or for influenza,” said Dr. Steve Toadvine, vice president at Baptist Health Lexington. “When it’s as commonly and as easily available, with rapid results.”
This story was originally published April 22, 2020 at 2:16 PM.
