Work done at Pacific Northwest National Laboratory in Richland has the potential to help save lives in future outbreaks of the deadly Ebola virus.
Researchers at the Department of Energy lab partnered with other institutions, including the University of Wisconsin-Madison, as the university had the rare opportunity to obtain blood samples from 20 patients sickened with the virus during a major outbreak that began in Africa’s Sierra Leone in 2014.
The samples allowed the study of molecular changes that occur in an individual’s blood during an infection, said PNNL scientist Thomas Metz, one of the corresponding authors of a study published in the journal Cell Host & Microbe. He was the metabolomics team lead.
PNNL’s role was to use sophisticated scientific equipment at the Environmental Molecular Sciences Laboratory at PNNL to analyze the blood samples.
The samples were chemically treated to deactivate the virus before shipping them to PNNL, eliminating any infection risk.
“Our team studied thousands of molecular clues in each of these samples, sifting through extensive data on the activity of genes, proteins and other molecules to identify those of most interest,” said Katrina Waters, the leader of the PNNL team and a corresponding author on the paper.
The sweeping study looked at everything from enzymes to lipids to molecules associated with the immune system.
The team produced what may be the most thorough analysis yet of blood samples from patients infected with the Ebola virus, Waters said.
Scientists identified 11 differences, or biomarkers, in the blood of the 11 patients who died and the nine who survived.
Two of those biomarkers, when screened for early in the illness, accurately predict which patients are likely to die.
Researchers found that L-threonine, an amino acid, and a vitamin-D-binding protein were present at lower levels when patients were admitted to hospitals and later died, compared with people who survived.
The finding means triage potential for patients, which helps health care workers prioritize scare resources in places such as Sierra Leone.
Those workers then can give care to the sickest patients, said Yoshihiro Kawaoka, a virology professor at the School of Veterinary Medicine at University of Wisconsin-Madison, and the senior author of the study.
“We want to understand why those two compounds are discriminating factors,” Kawaoka said. “We might be able to develop drugs.”
There also might be the potential to develop a field kit health care workers could use to test patients for the biomarkers and guide treatment, Metz said.
The study also uncovered other information about the illness.
The molecular signals in the blood of Ebola patients that were similar to patients with sepsis, a condition in which the body responds to infection by bacteria or other pathogens by mounting an inflammatory reaction that damages the body.
The Centers for Disease Control and Prevention report there have been 15,227 laboratory-confirmed cases in Sierra Leone, Guinea and Liberia, leading to 11,310 deaths.
It is believed to be an animal-borne illness, particularly in bats. If a person becomes infected, the virus can spread to others through direct contact.
Symptoms include severe bleeding, vomiting and fever.
There are few ways to study the disease other than during an outbreak.
Obtaining blood samples proved difficult until Kawaoka and others built a relationship with high-level officials in Sierra Leone.
With the approval of both patients and Sierra Leone’s government, health workers in 2015 collected samples from patients when they were diagnosed with Ebola and at multiple points thereafter.
Fifteen PNNL scientists contributed to the study.
Among the corresponding authors were Waters, Metz and Richard D. Smith.
Three more PNNL scientists — Jason P. Wendler, Jennifer E. Kyle and Kristin E. Burnum-Johnson — are among six scientists who share “first author” honors.
Other PNNL authors include Jon Jacobs, Young-Mo Kim, Cameron Casey, Kelly Stratton, Bobbie-Jo Webb-Robertson, Marina Gritsenko, Matthew Monroe, Karl Weitz, and Anil Shukla.