November 9, 2020
Web Feature

PNNL Researchers Shift Project’s Focus to Regional COVID-19 Patients

A project investigating molecular diagnostics for first responders pivots to learn more about the fundamental biology of the COVID-19 immune response

illustration of lungs with multicolored lines inside

Illustration by Donald Jorgensen | Pacific Northwest National Laboratory

At Pacific Northwest National Laboratory (PNNL), dozens of scientists are working to learn about the virus causing the COVID-19 pandemic. The laboratory also happens to be located in one of the hardest-hit counties in Washington State.

As a result, one PNNL research project has changed its focus from diagnostics for first responders in California to learning about some of the biggest mysteries of COVID-19 from patients in their immediate community.

Chemist Paul Piehowski and his colleagues recently started a pilot volunteer study in collaboration with Kadlec Regional Medical Center in Richland, Wash. For patients on ventilators, a plastic heat moisture exchanger captures moist air leaving their lungs. The researchers will collect those components and look for protein patterns unique to patients with COVID-19.

The information will give researchers a detailed look at the immune response in patients with the disease, possibly helping physicians understand why some patients get sicker than others and map out effective treatments. A common pattern might also be a useful signal in a future diagnostic breath test for COVID-19, Piehowski said.

portrait of a man looking at a computer
PNNL chemist Paul Piehowski looks for patterns in large-scale protein measurements that could be molecular signatures of cellular stress. (Photo by Andrea Starr | Pacific Northwest National Laboratory)

Pandemic shifts project’s focus

Last year, more than 15 PNNL researchers started working on a PNNL-funded project called BRAVE, which stands for Biomedical Resilience and Readiness in Adverse Operating Environments.

In this project, the researchers analyzed blood, urine, and saliva collected from Los Angeles County firefighters working a drill. The researchers looked for patterns in genes, proteins, and cellular metabolites that indicated physiological stress and predicted effects such as exhaustion and overheating.

Molecular stress signatures might be used to monitor the health and performance of first responders, perhaps enabling leaders to pull responders off the line before they’re at risk, said PNNL exposure scientist Justin Teeguarden, the principal investigator of BRAVE. Those molecular patterns also provide clues to changes in cellular function, which could help scientists develop treatments to speed recovery.

Exhaling pulls proteins from inside the lungs

Piehowski and his colleagues, experts in proteomics, look for molecular signatures in large-scale protein patterns. They use optimized mass spectrometry platforms to analyze thousands of proteins in clinical samples. Typically, that means working with blood and tissue samples.

a woman exhaling
Photo by MBLifestyle | Shutterstock.com

As part of BRAVE, the researchers planned to extend their hunt for biomarkers to exhaling, looking for signatures of an immune response to smoke exposure in the firefighters. The turbulent flow of exhaling pulls enough cells and particles from the lining of the lungs for the researchers to detect proteins related to an inflammatory immune response.

Then COVID-19 became widespread. The researchers realized their search for molecular stress signatures in the lungs could be used to learn more about the fundamental biology of the new disease. That information could help doctors and scientists understand features of COVID-19 immune response that explain the delay in the appearance of symptoms or why some patients get sicker than others.  

There was just one challenge: getting exhaled samples from patients connected to a machine that’s breathing for them. However, a piece of medical equipment provides a solution.

For patients on ventilators, a heat moisture exchanger recycles moisture from the air leaving their lungs. Measuring proteins on the filter inside this component is essentially a way to sample breath from patients who are not breathing on their own.

The researchers will measure proteins collected on these filters from patients ventilated at the hospital. They will look for patterns unique to patients with COVID-19 compared to patients ventilated for other medical reasons.

“Using this deep protein profiling technique, we might be able to see signatures of an early immune or inflammatory response specific to infection with the COVID-19 virus,” Piehowski said. “With a collection of unique molecular signatures for respiratory diseases like COVID-19, we hope to eventually develop breath-based diagnostic tests too.”

For protein analysis, the researchers use instruments at the Environmental Molecular Sciences Laboratory (EMSL), a U.S. Department of Energy Office of Science user facility at PNNL.

Published: November 9, 2020