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New Frontiers pilot awards support COVID-19 research

Frontiers: University of Kansas Clinical and Translational Science Institute has awarded three pilot grants to scientists studying COVID-19.

gloved handed holding a vile of a COVID-19-positive sample

If there is one thing the coronavirus pandemic has made clear, it's the necessity of translating, as quickly as possible, the discoveries made in medical laboratories into actual treatments, procedures and diagnostic tools that can help patients.

Frontiers: University of Kansas Clinical and Translational Science Institute has awarded three one-year $50,000 pilot grants to help scientists studying COVID-19 do exactly that.

Housed at the University of Kansas Medical Center, Frontiers accelerates research by connecting scientists to resources; facilitating collaboration among researchers, communities and institutions; and offering training. The institute is part of a network of 57 such hubs nationwide that are funded with a grant from the National Center for Advancing Translational Sciences of the National Institutes of Health.

"One of the ways we fulfill our mission is by awarding pilot grants that launch new research projects. When the coronavirus emerged, we decided to use that grant mechanism to help address the COVID-19 pandemic specifically," said Mario Castro, M.D., MPH, director of Frontiers and vice chair for clinical and translational research at KU Medical Center.

The awards provided an opportunity for researchers across the region to apply and to collaborate. "The pandemic has taught us to think outside our silos, and these pilot awards were available across different institutions," said Castro. "We need to be cooperating in a multidisciplinary fashion and sharing information to be able to quickly address this pandemic."

The Frontiers COVID-19 pilot awards were open to investigators from all Frontiers partner institutions: KU Medical Center (Kansas City, Wichita and Salina campuses); University of Kansas; University of Missouri-Kansas City; Kansas City University of Medicine and Biosciences; Children's Mercy Kansas City; St. Luke's Health System; and Kansas State University College of Veterinary Medicine.

"Because of the urgency of the pandemic, applicants for the new COVID-19 pilot awards needed to demonstrate that their research project could make an impact relatively quickly. Each of these winning projects does that, and each focuses on a different way to tackle the pandemic, from developing drugs to addressing the pediatric population to using large-scale databases to help us manage coronavirus cases," said Castro. "We hope that this is one of many opportunities we have at KU to help not only our population here but across the country as we figure out ways to address this pandemic."

More than 40 scientists submitted letters of interest. Of the eight investigators who were then asked to submit full applications, three were selected to receive an award.

Elin Grundberg, Ph.D.
Elin Grundberg, Ph.D.

Elin Grundberg, Ph.D.
Roberta D. Harding and William F. Bradley, Jr. Endowed Chair in Genomic Research
Children's Mercy Research Institute
Associate Professor of Pediatrics
University of Missouri-Kansas City School of Medicine
Department of Pathology and Laboratory Medicine 
University of Kansas Medical Center

Unlike children with other respiratory infections such as influenza, children infected with the novel coronavirus are less symptomatic and much less likely to develop severe illness than are infected adults. Elin Grundberg wants to learn why.

For her pilot COVID-19 project, she and her research team will compare nasal swab samples taken from children and adults who tested positive for the coronavirus. Because the epithelial cells in the nose are the entry point for the virus into the body, nasal samples enable the researchers to study the body's first cellular line of defense against the virus to see how it varies by age. They will also examine nasal samples from children with infections from other types of coronaviruses, which are common in kids but not in adults, on the hunch that children's exposure to other strains has bolstered their immunity to COVID-19.

The samples will come from consenting pediatric patients and adult health care workers at Children's Mercy in Kansas City. The research team will use single-cell genomic sequencing technology to compare cellular variations between samples. "With this technology, we can actually look at one cell at a time," Grundberg said. "That will allow us to find very small differences, or maybe even a total novel cell type, that we haven't been able to find before."

Grundberg also plans to research the genetics of those very few children who do develop severe cases of COVID-19. Hypothesizing that these kids have inherited from their parents a genetic predisposition to severe forms of the disease, she and her team will employ a technology called next-generation sequencing to detect mutations in the DNA of these children and their parents. These mutations could explain why a tiny subset of children develop severe cases of COVID-19.

Ultimately, she wants her findings to be used to help create treatments for COVID-19 and prevent a recurrence of the pandemic.

Anthony Fehr, Ph.D.
Anthony Fehr, Ph.D.

Anthony Fehr, Ph.D.
Department of Molecular Biosciences
University of Kansas

Anthony Fehr has been studying how various coronaviruses replicate and cause disease since he was a postdoc in 2012. Last year, before the emergence of SARS-CoV-2, the coronavirus that causes COVID-19, he had authored several studies showing that a particular enzyme called a macrodomain is critical for the ability of coronaviruses to replicate themselves and trigger disease.

"Every single coronavirus has this enzyme," said Fehr. "And we've shown over the past eight years that if you take this macrodomain out of the virus, that virus doesn't replicate well and it doesn't cause much, if any, disease in mice. That indicated to us that this would be a pretty good potential drug target."

But designing a new drug to hit that target, testing it in clinical trials and getting FDA approval can take up to 10 years. For his Frontiers COVID-19 pilot project, Fehr and his lab are testing 20 compounds already approved by the FDA that have the potential to inhibit this macrodomain.

They will first test the compounds' ability to inhibit the replication of mouse coronavirus in a cell culture. If any of these compounds are effective, they will test the ability of those compounds to inhibit the replication of SARS-CoV-2 specifically.

"I feel like it's our duty to try everything we can in this pandemic and test these compounds," said Fehr. "Even if these compounds don't work for SARS-CoV-2, this enzyme is so similar between all the coronaviruses that we should still continue working to identify compounds that can inhibit the enzyme for future coronavirus outbreaks."

Xing Song, Ph.D.
Xing Song, Ph.D.

Xing Song, Ph.D.
Research Assistant Professor
Center for Medical Informatics and Enterprise Analytics
University of Kansas Medical Center

When hospitals become overwhelmed with patients during crises such as the coronavirus pandemic, health care workers are forced to ration care. Triage protocols are often used to determine what patients get priority for scare, life-saving resources such as ventilators.

These protocols rely on severity scoring systems that tend to be generalized for an intensive care unit, but do not consider all the risk factors for respiratory diseases such as COVID-19. For her Frontiers COVID-19 pilot project, Xing Song wants to create one that does.

Song plans to leverage a data repository for COVID-19 patients created and shared by the Greater Plains Collaborative, a research network of 12 medical centers, to develop a robust scoring system designed for a respiratory pandemic. The new system will utilize data elements absent from other systems, such as lymphocyte count and D-dimer levels. These laboratory data have been found to predict the severity of COVID-19.

Song and her group will then apply a sophisticated statistical model and machine learning to these data to develop a new scoring system that will determine who is most likely to benefit from a ventilator and who has a more severe condition. But she stresses that the system they develop will deliver much more than just a number.

"It will also provide all the risk factors that contribute to the score," said Song. "If the model tells the physician, 'this COVID-19-positive [case] has a higher likelihood of prolonged mechanical ventilation,' it will also provide an ordered list of factors that contributed to that score, such as pre-existing comorbidities, abnormal labs or vital signs."

Although the system is designed for a respiratory epidemic, Song believes the system she is creating has broader applications. "The structure for the scoring system we are creating could be applied to many other diseases," she said.

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