Today, the Benaroya Research Institute at Virginia Mason (BRI) announced four new COVID-19 research grants and updates related to existing COVID-19 research happening at the Institution that totals more than $5.8 million dollars funded by the National Institutes of Health (NIH).
The new grants, like BRI’s other COVID-19 research, leverage BRI’s expertise in the immune system and its intersection with disease, which is central to understanding COVID-19—not just whether a person becomes infected, but also the severity of the infection and how it resolves. One study is part of a larger, national effort and examines the immune responses in people hospitalized with COVID-19 to uncover markers that may predict a more severe infection and for those recovering, more insights into an effective immune response; another looks at the site of COVID-19 infection in lung tissue to identify ways to interrupt, slow or stop the infection; one studies an overactive, inflammatory immune response that occurs in some very severe cases; and the fourth studies two strains of the virus—circulating locally in Seattle—and how each may lead to different immune responses and disease severity.
"I am proud of BRI’s rapid response to researching COVID-19," said BRI President Jane Buckner, MD. "Our vision is for a healthy immune system for every individual. As part of that work, we lend our immunology expertise and tools to help uncover answers to the COVID-19 puzzle—why some people experience a more severe infection, to what underlying factors may dictate a worse infection."
These new grants build upon a dozen other COVID-19 research efforts happening at BRI, a testament to BRI’s agile infrastructure and strong clinical connections with Virginia Mason Health System, which allow it to quickly translate work from the lab to the clinic. For example, more than 30 Virginia Mason team members and BRI researchers are collaborating to study patient blood samples, expediting multi-year processes and regulations to just a matter of weeks.
The research teams at BRI are hopeful that their quick, collaborative work can yield new pathways for clinical solutions. This announcement follows a surprising BRI discovery recently published in the Journal of Allergy and Clinical Immunology that found individuals with asthma and allergies were less susceptible to the virus’ infection.
Details for each new NIH-funded COVID-19 grant include:
"Examining Immune Responses in People Hospitalized with COVID-19"
Jane Buckner, MD
$2,600,000
This research is part of a larger national project involving 10 institutions that aims to track the immune responses of people hospitalized with COVID-19 called the COVID Immunophenotyping Study (IMPACC) by the National Institute of Allergy and Infectious Diseases. Jane Buckner, MD is the principal investigator overseeing a team at BRI that is performing RNA sequencing on an anticipated 6,000 upper respiratory samples to identify biomarkers of COVID-19 disease progression and help identify novel therapeutics to treating it. The BRI team will work with the other study sites around the U.S. to analyze and integrate all the data sets generated through this project. Team members working on this grant include Matt Altman, MD, MPhil; Scott Presnell, PhD; Charlie Quinn, Vivian Gersuk, PhD and the Genomics Core; and Bernard Khor, MD, PhD. The study is 14 months long.
"Studying Two Strains of COVID-19 and the Cellular Immune Response in People with Varying Levels of Disease"
William Kwok, PhD
$1,400,000
There is almost no data yet on the human cellular response to the virus, so BRI researchers will examine cellular immune responses in people with different levels of disease symptoms, from mild to severe. The BRI team will look at the two major strains of SARS-CoV-2 circulating in the Seattle area and evaluate whether these strains lead to different immune responses and disease severity. Understanding aberrant immune responses in the severe disease group should enable us to design appropriate approaches for treatment. William Kwok, PhD is the principal investigator on the study that has recently been granted $1.4 million by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The team includes Erik Wambre, PhD; Peter Linsley, PhD; Carmen Mikacenic, MD; and Virginia Mason's Uma Malhotra, MD.
"Understanding the COVID-19 Infection in Lung Tissue"
Steve Ziegler, PhD
$1,122,000
This 14-month grant helps BRI look at the response of the lung’s epithelial cells, the barrier where COVID-19 infection occurs and where the virus replicates. Led by Steven Ziegler, PhD, using a model system referred to as "a lung in a dish," his team will closely examine how immune cells respond to the virus and to infected epithelial cells. This can lead to an understanding of how the virus gets into the cells and potential pathways or genes that can be manipulated to help resist the infection from occurring or replicating. The team includes Adam Lacy-Hulbert, PhD; Jessica Hamerman, PhD; and Daniel Campbell, PhD, as well as Seattle Children's Research Institute's Jason Debley, MD, MPH.
"Exploring an Overactive Inflammatory Immune Response to COVID-19"
Jessica Hamerman, PhD
$609,000
This 17-month research effort will look at an inflammatory syndrome called cytokine storm that occurs in some people with severe COVID-19. The BRI team seeks to identify if cytokine storm in COVID-19 patients is similar to the inflammatory disorder secondary hemophagocytic lymphohistiocytosis (HLH), and to discover if markers of HLH can identify patients early during disease who may benefit from particular therapies. Other investigators include Virginia Mason’s Uma Malhotra, MD and Carmen Mikacenic, MD, who will be joining BRI’s faculty in July.
There are a dozen other COVID-19 research projects happening at BRI, including:
"How COVID-19 Impacts the Immune System Differently in People"
Through this ongoing partnership with Virginia Mason, BRI is studying blood samples from patients infected with COVID-19 to explore what predicts whether someone will have a good or poor outcome. In a later phase of the project, the team will look at people who have recovered from COVID-19 and are still susceptible or protected from future bouts of infection. The lead investigators include BRI’s Jane Buckner, MD, Cate Speake, PhD and Virginia Mason’s Uma Malhotra, MD and 30 team members across both institutions.
