BRI scientists were sure of one thing when the novel coronavirus struck: They had the expertise to make swift progress toward understanding it and finding better treatments.
“Studying how the immune system responds to viruses has been part of our work for years,” says BRI’s President Jane Buckner, MD, “so we were poised and ready to play a key role in fighting COVID-19.”
It normally takes years to fund and launch major research, but our team has kicked off several studies in a matter of weeks. We’re investigating some of COVID-19’s biggest questions and pursuing answers that could stop it in its tracks. Our amazing community stepped up with more than $350,000 in donations to our COVID-19 Rapid Response Fund to make this research possible. BRI has since earned $5.8 million in grant funding from the National Institutes of Health to continue this work.
“The virus is so new that our research is like solving a jigsaw puzzle, except we don’t know where the edges are or what the picture looks like,” says BRI Affiliate Investigator Matt Altman, MD, MPhil. “We have to start from nothing and learn everything we can, as fast as we can.”
Why does COVID-19 make some people sicker than others?
It’s easy for BRI researchers to see their work’s potential impact: Our main building is across the street from Virginia Mason Medical Center, where dozens of patients have come for COVID-19 treatment. Some of these patients have mild symptoms and get better on their own, while others need critical care.
BRI and Virginia Mason launched a rapid-response research effort to understand why the virus affects people so differently. This research capitalizes on our decades of experience recruiting patients and investigating immune activity. And it wouldn’t have been possible without private donors.
“We’re using blood samples from Virginia Mason COVID-19 patients to study several key questions,” says Cate Speake PhD, “and we hope this leads to a test that could predict if a patient will have severe symptoms, so their doctors can be ready with the right treatments.”
How does the immune system fight off COVID-19?
When the National Institute of Allergy and Infectious Diseases (NIAID) launched a study examining how the immune system reacts to the new coronavirus, they knew they wanted Dr. Altman and Scott Presnell, PhD, on their team. The scientists had developed a way to collect samples and analyze millions of data points from asthma patients — and their method could shed light on COVID-19.
Dr. Altman and Dr. Presnell received a $2.6 million grant as part of a larger study led by Dr. Buckner, where BRI is among 10 institutions analyzing samples from over 2,000 COVID patients, resulting in 6,000 biological samples being analyzed at BRI.
That’s no small task: Each sample holds as much information as a lengthy novel.
“People sometimes make the analogy that it is like reading War and Peace thousands of times and looking for typos,” Dr. Altman says.
That’s where Dr. Presnell comes in: He uses bioinformatics to quickly sift through that information and pinpoint which genes are turned on and off in the body’s airway during COVID-19.
“This could illuminate whether certain genes help fight COVID-19 or lead to some of the damaging effects we are seeing, which could lead to therapies that modulate those genes so more people can overcome the virus,” Dr. Presnell says.
How does COVID-19 affect the lungs?
Steve Ziegler, PhD, is also investigating how the body fights off COVID-19. He studies epithelial cells in the lungs. These cells are supposed to respond to invaders like viruses, but they can mistakenly overreact to things like pollen.
“Overall, we’re interested in learning how your body decides what to fight and why it can go wrong,” Dr. Ziegler says.
Dr. Ziegler’s team recently earned a supplemental grant to add COVID-19 to their research on asthma. Using a model which he likens to “a lung in a dish,” his team will closely examine how immune cells respond to the virus, to learn more about how the body battles against it.
“This will help us understand what a healthy response looks like and how we might help people who don’t have a healthy response,” he says.
How does your body respond to different strains of coronavirus?
Bill Kwok, PhD, is on a quest to learn more about how the T cells in your immune system respond to different strains of the virus. His team hopes to learn if various strains of the virus lead to different immune responses and whether these different immune responses are correlated with clinical symptoms.
“Understanding what’s different about the immune system reaction, especially in people with more severe symptoms, could help us design treatments to fight off the virus,” Dr. Kwok says.
Why does the immune system go into overdrive?
Some COVID-19 patients have mild symptoms at first, then get significantly sicker a few days later. Their oxygen levels plummet and they may even need a ventilator.
Many researchers including BRI’s Jessica Hamerman, PhD, believe this response could happen because of an immune system response called a cytokine storm. Cytokines are proteins that are supposed to help your immune system fight off invaders like bacteria and viruses — they act like a fire alarm calling in immune cells to fight the infection. When the infection is gone, the fire alarm goes off and your immune system relaxes. But Dr. Hamerman likens a cytokine storm to a fire alarm that won’t turn off — your immune system keeps calling in more firefighters, even when the fire is out.
“The firefighters keep coming, spraying water and doing a lot of damage to your home if the alarm never stops,” she says. “Similarly, the cytokines keep calling in immune cells that make a lot of toxic molecules that can cause tissue damage and severe problems like pneumonia. The virus isn’t making these patients sick — it’s their immune system’s response to the virus.”
Dr. Hamerman recently earned a grant to study this response, working with several collaborators including Virginia Mason’s Uma Malhotra, MD, BRI’s Carmen Mikacenic, MD, and BRI Biostatistician Tee Bahnson.
“We already have some tools for treating cytokine storms when they’re triggered by autoimmunity, by other infections or when caused by a genetic condition—a set of syndromes called hemophagocytic lymphohistiocytosis (HLH),” Dr. Hamerman says. “We want to see how similar these responses are and if biomarkers that inform therapies for HLH patients will also work for cytokine storms caused by COVID-19.”
Can we find better treatments for severe COVID-19?
Long before the pandemic, Carmen Mikacenic, MD, had to tell many patients and families that going on a ventilator was their only hope — and there was no way to predict if it would work. Now, many patients with severe COVID-19 are hearing the same thing and Dr. Mikacenic wants to be able to give them better answers.
Dr. Mikacenic, BRI’s newest principal investigator who comes to us from the University of Washington, is a pulmonologist and critical care doctor. She treats patients with lung problems like acute respiratory distress syndrome (ARDS). ARDS is a condition where fluid collects in the lungs, making it hard or impossible to breathe. It’s also a common COVID-19 complication.
“We put patients on ventilators to support them while their body fights off the disease, but we don’t have therapies to fix the underlying condition,” Dr. Mikacenic says.
That’s why she’s on a quest to learn more about why people develop ARDS, how to better predict their outcome, and find new treatment options. She’ll be receiving a grant to learn more about how ARDS affects patients including those with COVID-19.
“When someone develops ARDS, I want to be able to tell their family if a ventilator will help and, eventually, that we have a treatment to address what’s causing their lung problem,” Dr. Mikacenic says. “This research brings us closer to that.”
BRI as part of the solution
Not only have BRI scientists managed to launch these studies rapidly — they’ve done this from home, and by working seven days a week. While COVID-19 still holds many mysteries, our team is agile, and knows how to lean into a scientific challenge and relentlessly work to solve it.
“Every day, we chip away at scientific mysteries and pursue cures for diseases like multiple sclerosis and diabetes — and we believe this is something we can accomplish,” Dr. Speake says. “That’s why I know we can help with COVID, too: Our team and the scientific community at-large have come together, and we’re giving everything we have to fight it.”
Originally published in BRING IT ON newsletter - Summer 2020
July 10, 2020
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