Some patients who become seriously ill or die from common respiratory viruses have abnormally high levels of an important enzyme, new Australian-led research has found.
The discovery may help provide part of the answer to why otherwise healthy people sometimes die from infectious diseases, while others fight off viruses unscathed.
Led by Professor Katherine Kedzierska, a viral immunologist at the University of Melbourne’s Doherty Institute, researchers analyzed the blood of patients admitted to hospital with one of three viruses; severe seasonal flu, Covid or RSV.
They also analyzed samples from children experiencing an inflammatory condition associated with Covid.
The scientists found that an enzyme known as oleoyl-ACP hydrolase (Olah) was highly elevated in some of the sickest patients, including some who died.
“Everyone has low levels of Olah, and it’s a very important enzyme because it’s involved in the production of fatty acids, which are components of lipids,” Kedzierska said.
Lipids are fats that are critical for forming cell membranes and storing energy in the body.
“But in some patients who develop life-threatening diseases, Olah is produced at significantly higher levels, while we find very low levels in healthy individuals and patients with mild diseases,” she said.
Dr. Brendon Chua, a viral and translational immunologist, further investigated the findings by examining the impact of Olah on mice. His team found that mice genetically engineered to lack the Olah enzyme had less severe viral infections, less pneumonia and higher survival rates.
The researchers suggested that Olah may be associated with the lipids that stimulate macrophages, which are a type of white blood cell that engulf and kill pathogens.
Although boosting these lipids may seem beneficial when fighting a virus, excessively high levels of Olah can lead to an overactive immune response and harmful levels of inflammation.
The findings were Published on Tuesday in the prestigious scientific journal Cell.
Kedzierska said she now hopes to conduct larger studies to investigate whether Olah is a useful marker for predicting which patients will experience severe symptoms and therefore require closer monitoring and care.
The findings are “interesting and exciting science”, said Prof Peter Openshaw, a respiratory physician and immunologist at Imperial College London.
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“The investigators and the journal are excellent, which lends more credence to the findings,” he said.
He said further research is needed to determine whether Olah levels are the cause of the effect of severe disease, or whether Olah levels are also affected by other inflammatory conditions.
Allen Cheng, a professor of infectious disease epidemiology at Monash University, described the researchers’ finding as potentially advancing understanding of why some people get serious infection and others don’t.
But Cheng said “there are still many questions,” such as whether lipids and macrophages are the only important pathway for determining which patients develop severe disease, and whether there are opportunities to intervene to improve outcomes for those patients.
Kedzierska said she hopes ongoing research on Olah will answer some of these questions.
“We’re really hoping to understand high-risk groups more, for example pregnant women, and people with comorbidities like obesity,” she said.
The team is now working to develop and test Olah-based diagnostic methods to screen hospitalized patients on admission.
