One of the most confounding elements of the COVID-19 pandemic is the large number of people who can be infected with the virus but not have symptoms.
The Centers for Disease Control and Prevention (CDC) has estimated that the number of Americans infected with the virus might be 10 times higher than currently estimated, as many as 24 million people.
Dr. Craig Forrest
In late July, the University of Arkansas for Medical Sciences (UAMS) began high-accuracy COVID-19 antibody testing to determine the prevalence of COVID-19 infection in Arkansas with the goal of providing information to help make decisions about how and when to reopen.
UAMS Chancellor Dr. Cam Patterson said, “It will be critical for policymakers to estimate how many Arkansans have been previously infected as they consider reopening schools, allowing mass gatherings and keeping workplaces safe.”
Dr. Josh Kennedy
When they started in July, UAMS researchers were only able to process up to 180 samples per day by hand. By early August, a robotic-assisted immunoassay machine capable of processing 2,500 samples per day was expected to be in use. The research funded by a $3.3 million grant will collect blood samples from nearly 7,500 Arkansas adults and children through October.
Dr. Laura James, director of the UAMS Translational Research Institute, said while it isn’t possible right now to test everyone in the state, a program can be designed that will give an estimate of how many Arkansans have had COVID-19.
A positive antibody test means a person was exposed to the virus and developed antibodies against the virus. Antibody tests have been controversial — there are at least 15 different tests, some with dubious accuracy.
Dr. Karl Boehme
“Many tests on the market have proven to be inaccurate or provide no useful information beyond a positive or negative result,” said Dr. Craig Forrest, associate professor in the UAMS College of Medicine Department of Microbiology and Immunology. “We’re confident we have a test that’s reliable and meaningful and will serve Arkansas well. Both the sensitivity and specificity of the laboratory-based test is 100 percent. This is paired with an FDA-approved commercial test that will be implemented through the Department of Pathology at UAMS to increase the power of the assay through the use of two unique platforms for analysis.”
Forrest said this test provides a great opportunity for scientists to apply their skillset to a question that has huge public health ramifications. Not just for Arkansas but potentially worldwide.
The lab component was developed in early March by Forrest; Dr. Josh Kennedy, an associate professor in the UAMS departments of pediatrics and internal medicine; and Dr. Karl Boehme, associate professor in microbiology and immunology. The UAMS antibody test requires a small amount of blood. Its validity testing shows it is not fooled by antibodies for other coronaviruses — a problem with some of the other antibody tests.
UAMS is using two different testing platforms. One is FDA-approved. The second is an adaptable and scalable research-directed test designed to be more “nimble,” so it can be adjusted as necessary as new information about immunity becomes available. UAMS may seek FDA approval for this test in the future.
From the scientific perspective, knowing the number of people infected will give researchers an idea of how much of the state’s population is still at risk for COVID-19.
“If a significant number of people have antibodies to the virus, say 70 or 80 percent, that indicates that at least that percent of Arkansans has been exposed to the virus and should have some level of immunity — hopefully protective,” Boehme said. “That also suggests that some in the remaining 20-30 percent remain susceptible and could be at risk for severe complications. In contrast, if we find that a small percentage of the population, say 10 percent, has antibodies, that would suggest that the vast majority of the state is still at risk. This could give the policymakers important information to decide when new or additional precautions should be implemented or, fingers crossed, we are safe to resume business as normal.”
Testing might be broadened later to see who might be able to go out to resume normal work and play activities. “We are building capacity and infrastructure to expand testing, as needed,” Boehme said.
Boehme added that antibodies are vital for helping clear the infection. They stick around for several weeks to potentially years after the person has recovered, and it is hoped to prevent reinfection or at least limit the severity of reinfection.
“So, for the purposes of our study, antibodies are an indicator of whether a person was previously infected and likely has some level of protection from the virus,” he said. “There are many asymptomatic cases of COVID-19, and these patients often don’t know they are infected.
But the antibody test can tell us that they have been infected and give us a better sense of how many people who did not have a positive test have been infected.”
Information also possibly could be used to identify people with COVID-19 antibodies who might be able to donate plasma to be made into medicine for hospitalized COVID-19 patients.
“It is my understanding the Arkansas Blood Institute is testing donors for antibodies with every donation,” Kennedy said. “Persons who have antibodies could be contacted to donate plasma for therapeutic purposes. Ideally, we would want to know that a person donating has what we call ‘high-titer’ antibodies, meaning that the person has a large quantity of antibodies that recognize the virus present in their blood/plasma. This would be an ideal donor, and the test that we are currently running in the laboratory is capable of determining the amount of these specific types of antibody present. This differs from most commercially available tests at the moment, as they only provide a ‘yes or no’ type evaluation of virus-specific antibodies — are they present or not?”
Kennedy said this current study will help the state balance keeping as much economic activity going as possible while still protecting our most vulnerable citizens and maintaining the capacity of our health care system.
“Being able to get an accurate count of how many people have been infected may impact how aggressive we can be with efforts to reopen the economy,” Kennedy said.
The epidemiology component of the testing is being led by College of Public Health Dean Mark Williams and Benjamin Amick, associate dean for research. Key College of Public Health team members are epidemiologists Wendy Nembhard, Victor Cardenas and Lori Fischbach, and biostatistician James Selig. Significant UAMS guidance and resources have also come from Shuk-Mei Ho, vice chancellor for research and innovation and Stephanie Gardner, provost, chief academic officer and chief strategy officer.
Other collaboration and support have come from the Translational Research Institute and the National Center for Advancing Translational Sciences including its informatics core, led by Fred Prior, chair of the Department of Biomedical Informatics in the College of Medicine. Other collaborators from the College of Medicine include Dr. Erika Olgaard, assistant professor in the department of pathology; Dr. Jeff Moran, assistant professor in the department of pharmacology and toxicology, who will oversee the robotic component of the study; and Dr. Jessica Snowden, associate professor in the department of pediatrics, who will oversee the pediatric component.
“This is truly a team science effort involving the expertise of diverse but complementary experts who have come together to develop a solution to address COVID-19 in Arkansas,” James said.
Boehme said the antibody testing will serve as a springboard for researchers to answer deeper questions about COVID-19 in other studies, such as:
• How many antibodies are present when tested?
• How robust is the immune response?
• How much antibody is required to provide immunity?
• How long does immunity last?
“For other coronaviruses, the antibody response may wane after a year or two,” Boehme said. “The duration of immunity has implications for a vaccine; will the vaccine be effective for life or will it be a yearly vaccine like with the flu?”
