Northwestern’s Thomas McDade aims to track coronavirus infections and explain social inequalities by neighborhood, one drop of blood at a time.
With the COVID-19 pandemic prompting untold thousands of researchers to pivot their work to the coronavirus, much of the effort has naturally played out within such fields as molecular biology, virology, and immunology. Nevertheless, scientists from other disciplines have also joined the fray.
One such researcher is Thomas McDade, PhD, of Northwestern University in Evanston, Illinois. His work occupies a niche at the intersection of biology and anthropology, investigating how biomedical factors such as inflammation, tracked over time and combined with lifestyle and environmental data, can predict rates of cardiovascular disease, obesity, and other health problems within given populations.
In the face of COVID-19, McDade has turned one of his longtime data-gathering techniques — a low-tech, minimally-invasive method for collecting blood samples — to new use in tracking the pandemic: With his colleagues at Northwestern, he devised a blood test for antibodies to the coronavirus, allowing detailed monitoring of exposure to the SARS-CoV-2 virus in specific geographic areas.
In the face of COVID-19, McDade has turned one of his longtime data-gathering techniques — a low-tech, minimally invasive method for collecting blood samples — to new use in tracking the pandemic.
For more than 20 years, McDade has gathered samples from the field by extensive use of “dried blood spot” (DBS) technology, a blood-collection technique in wide use in the United States since the 1960s in hospital-based screening programs for newborn babies.
With DBS cards, there’s no need for study participants to visit a lab or clinic to have their blood drawn. Instead, the cards can be distributed via mail and returned the same way, after participants have pricked a finger and deposited a blood droplet on the card. This method has enabled McDade to follow research participants from areas as far-flung as the Philippines (the site of a decades-long study on the relationship between inflammation and lifestyle factors such as diet and overall health), the deserts of northern Kenya, the Amazon basin of South America, and the tropical islands of Samoa.
In adapting the DBS method to track the coronavirus, McDade and his colleagues will screen for antibodies to SARS-CoV-2 in populations in the Chicago area segmented by individual zip codes. The team aims to ascertain why certain demographic groups — especially Black and Latino people—have suffered higher COVID-19 infection and death rates than other ones.
On The Spot
McDade’s work in the Philippines was just one of many of his ongoing research projects — until COVID-19 came along. At that point, the scientist and his family were added to the legion of the locked-down, as the pandemic first gained traction in the U.S. in March. With Northwestern’s campus declared off-limits, McDade found himself idle. But not for long.
“Even as my family and I were getting over the recalibration to the new normal,” he says, “I’d been thinking about the problem, and I realized there was something I could do in terms of finding out how and where the virus was spreading in the community. Antibody testing is a great tool because it allows you to look back in time to determine who’s been exposed.”
With that, the idea of a DBS-based antibody test for coronavirus infection was born.
Fortunately, McDade was granted special access to campus, and his Northwestern colleagues provided indispensable help. “Some colleagues at the medical school were developing a serum-based test for antibodies… and they were immediately collaborative in sharing key materials. I took the materials into my lab and, in parallel with their serum protocol, developed a blood-spot protocol. Adapting the DBS technique was the real innovation, as there aren’t many off-the-shelf products for assaying biomarkers in dried blood.”
“Adapting the ‘dried blood spot‘ technique was the real innovation, as there aren’t many off-the-shelf products for assaying biomarkers in dried blood.”
Inevitably, the project entailed some scrambling — in one instance quite literally, when McDade was forced to hunt down a package containing a crucial enzyme, after it couldn’t be delivered to his officially closed lab building.
The need for funding necessitated a different kind of effort. Although Northwestern provided some initial money, McDade pursued several funding agencies without success until, in May, the National Science Foundation came through with $200,000. This sum has allowed McDade and colleagues to begin sending out the first of a projected total of 3,000 screening kits to the Chicago area. Research participants can use a smartphone or computer to access a homepage on which to fill out a consent form and a survey; the antibody test results are subsequently combined with survey data.
“It costs about one dollar to get a sample,” says McDade. “Most people don’t care that much about having their finger stuck, and once you put the blood on paper, the sample is dried and preserved. And it contrasts with some of the earlier tests for coronavirus seroprevalence, which used venous blood samples from a small number of hospitalized people — so, in no way representative of the general population.”
Recently, McDade and colleagues have also used the DBS method to identify an elevated prevalence of SARS-CoV-2 antibodies in a sampling of families of essential workers. The results suggest a high rate of transmission among household members.
Context is All
This search for a deeper context behind human biology and health has animated McDade’s work from his days as a pre-med in college.
“I thought I was going to medical school. But I realized fairly early on that I was less interested in the practice of medicine and more interested in research. In particular, in how context matters in human biology — where people live, how they grow up, and how that shapes their physiology and health,” he says.
McDade’s embrace of biological anthropology included traveling to Samoa for his dissertation — a deliberate nod to the iconic work of Margaret Mead, whose 1928 book Coming of Age in Samoa examined sexual mores among Samoan adolescents. In the decades after its publication, the book has stirred controversy, with equally fervent attackers and defenders debating Mead’s fieldwork and interpretations.
“As a grad student I was particularly interested in stress and how that affects the human immune system in the context of adolescence and development,” says McDade. “So I went there to do my dissertation because of the Margaret Mead controversy, to examine the extent to which adolescence is a stressful time of life in that part of the world.
“DBS sampling allowed me to collect blood from adolescents in Samoa, and to analyze them for markers of immune function. Even though the adolescents in my study reported low levels of stress or depression, the immune measures revealed that stressors associated with rapid cultural and economic changes in Samoa were taking a physiological toll.”
In his subsequent work around the world, McDade has investigated a range of social phenomena and disparities — including economic status, parenthood, upbringing, exposure to infectious microbes, and diet — and their measurable effects on health outcomes.
Inflammation & Environment
At the moment, McDade’s research in the Philippines is suspended, as that nation faces its own battle against the pandemic. However, he has accumulated decades of data on environmental exposures and their role in inflammation, and how the latter, in turn, affects cardiovascular disease, metabolic disease, accelerated aging, and other health problems. (A 2008 report, for example, examined obesity and pathogen exposure in Filippino women as a predictor of elevated levels of C-reactive protein, a biomarker for inflammation.)
Of particular interest is the role of the infectious-disease environment in the development of the immune system. Evidence suggests that greater exposure to microbial pathogens in infancy, seen more frequently in the Philippines, shapes the immune system and its heightened management of inflammation later in life. This contrasts with nations such as the US, where sanitary conditions ensure that children generally have lower microbial exposure in infancy.
For now, McDade is devoted to his work on COVID-19. He is talking with Illinois public-health authorities to expand the DBS testing. Even more importantly, McDade and his colleagues are developing another assay to test for neutralizing antibodies to the coronavirus — evidence that people who have been infected with SARS-CoV-2 have built up immunity to future exposure.
“Right now we’re pushing hard to get a blood-spot neutralizing antibody protocol up and running,” he says, “We hope to have that within a few weeks.”
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