A Less-Than-Perfect COVID-19 Test Shows Promise
Like Diehl, Botten has had his hands in multiple COVID-19 projects since early in the pandemic. An expert on pathogenic RNA viruses, Botten’s first—and most immediately
impactful—project was his work with Emily Bruce, Ph.D., faculty scientist in medicine, Crothers and others in developing and studying an alternative COVID-19 diagnostic test. The method for the test, published first in a BioRxiv preprint and
more recently in the journal
PLOS Biology, omits the step in the widely used reverse transcription polymerase chain reaction (RT-PCR) test, considered the gold standard of COVID-19 diagnostics, where the scarce reagents are needed. Shared widely on Twitter, the preprint
was downloaded 18,000 times and the abstract was viewed 40,000 times.
A critical connection between Crothers and Keith Jerome, M.D., Ph.D., director of the University of Washington’s Molecular Virology Lab, provided the perfect partnership
for examining the test’s accuracy on a broader scale. The site of the first confirmed U.S. COVID-19 case, Washington had far more cases than Vermont—more than 1500 people had already tested positive by March 20—and Jerome’s
lab had plenty of samples with a wide range of viral load to study.
The UVM test correctly identified 92 percent of the positive sample and 100 percent of the negatives, only failing to catch the positive samples with exceptionally low
levels of the virus. Public health experts increasingly believe that ultra-sensitive tests that identify individuals with even the smallest viral loads are not needed to slow spread of the disease.
“You can go for the perfect test,
or you can use the one that’s going to pick up the great majority of people and stop transmission,” says Botten. “If the game now is focused on trying to find people who are infectious, there’s no reason why this test shouldn’t
be front and center, especially in developing countries where there are often limited testing programs because of reagent and other supply shortages.”
Botten, Bruce and colleagues’ test is now being run in labs worldwide through
a program called PROPAGATE, run by the Health and Environmental Sciences Institute (HESI), a non-profit that marshals scientific expertise and methods to address a range of global health challenges. HESI Director Syril Pettit, Dr.PH., saw the preprint
and reached out to Botten in April and the relationship has yielded great momentum for the research.
Pivot Once, Pivot Twice
In some cases, great concepts for adapting existing research were halted, due to lack of funding. Stapleton, a pulmonary and critical care specialist, was already three years into a National Institutes of Health-funded clinical trial examining the use of cycle ergometry and amino acid supplementation in ventilator-dependent patients with acute respiratory failure. She and her collaborators at Johns Hopkins and Queens University realized an opportunity to target their focus on COVID-19 patients who had been on ventilators. She applied for a supplement to the R01 grant for a cohort study investigating these patients’ inflammation and immune response outcomes over the course of a year and, using existing resources, she and her colleagues began enrolling participants.
Ultimately, the supplement did not secure funding, but with the blood samples her team had already obtained, she teamed up with Professor of Medicine and Chief of Cardiology David Schneider, M.D., to develop a study on biomarkers for thrombosis in COVID-19 patients. “Recent reports have noted that thrombosis complicates 16 percent of hospitalizations and thrombosis is a key contributor to respiratory failure,” says Stapleton.
While the grant won’t be reviewed until April 2021, Stapleton continues to be involved in SARS-CoV2 research. In collaboration with Botten, she’s enrolling COVID-19 positive patients for his lab’s work developing human monoclonal antibodies as a therapeutic for COVID-19.