by Some patients who become seriously ill or die from common respiratory viruses have unusually high levels of a vital enzyme, a new Australian-led study has found.
The discovery may help answer part of the question of why otherwise healthy people sometimes die from infectious diseases while others survive viruses unscathed.
Led by Professor Katherine Kedzierska, a viral immunologist at the University of Melbourne’s Doherty Institute, researchers analyzed the blood of patients hospitalized with one of three viruses: severe seasonal flu, Covid or RSV.
They also analyzed samples from children suffering from an inflammatory disease associated with Covid.
The scientists found that levels of an enzyme called oleoyl-ACP hydrolase (Olah) were greatly increased in some of the most seriously ill patients, including some who died.
“Everyone has low levels of Olah, and it’s a really important enzyme because it’s involved in the production of fatty acids, which are components of lipids,” Kedzierska said.
Lipids are fats that are crucial for the formation of cell membranes and the storage of energy in the body.
“But in some patients who develop life-threatening disease, Olah is produced at much higher levels, while in healthy individuals and patients with mild disease we see very low levels,” she said.
Dr. Brendon Chua, a virologist and translational immunologist, investigated the results further by studying the effects of Olah in mice. His team found that genetically modified mice lacking the Olah enzyme suffered less severe viral infections and pneumonia and had higher survival rates.
The researchers suspect that Olah may be related to the lipids that stimulate macrophages, a type of white blood cell that ingests and kills pathogens.
While promoting these lipids may seem helpful in fighting a virus, too high Olah levels can lead to an overactive immune response and harmful levels of inflammation.
The results were published on Tuesday in the renowned 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 results are “interesting and exciting scientific findings,” said Prof. Peter Openshaw, a pulmonologist and immunologist at Imperial College London.
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“The researchers and the journal are excellent, they give additional confidence to the results,” he said.
He said further research is needed to determine whether Olah levels are the cause of the effects of severe disease and whether Olah levels are also affected by other inflammatory diseases.
Allen Cheng, professor of infectious disease epidemiology at Monash University, described the researchers’ discovery as one that may contribute to a better understanding of why some people experience severe infection and others do not.
But Cheng said there are “still many unanswered questions,” such as whether lipids and macrophages are the only important signaling pathway in determining which patients will experience severe disease, and whether there are ways to intervene to improve outcomes for these patients.
Kedzierska said she hopes ongoing research on Olah will answer some of those questions.
“We really hope to better understand high-risk groups, such as pregnant women and people with comorbidities such as obesity,” she said.
The team is currently working on developing and testing Olah-based diagnostic methods to screen hospital patients upon admission.
