https://www.scienced...10824135358.htm
An enzyme with an elusive role in severe inflammation may be a key mechanism driving COVID-19 severity and could provide a new therapeutic target to reduce COVID-19 mortality, according to a study published in the Journal of Clinical Investigation.
Researchers from the University of Arizona, in collaboration with Stony Brook University and Wake Forest University School of Medicine, analyzed blood samples from two COVID-19 patient cohorts and found that circulation of the enzyme -- secreted phospholipase A2 group IIA, or sPLA2-IIA -- may be the most important factor in predicting which patients with severe COVID-19 eventually succumb to the virus.
sPLA2-IIA, which has similarities to an active enzyme in rattlesnake venom, is found in low concentrations in healthy individuals and has long been known to play a critical role in defense against bacterial infections, destroying microbial cell membranes.
When the activated enzyme circulates at high levels, it has the capacity to "shred" the membranes of vital organs, said Floyd (Ski) Chilton, senior author on the paper and director of the UArizona Precision Nutrition and Wellness Initiative housed in the university's College of Agriculture and Life Sciences.
The research team was able to analyze thousands of patient data points using machine learning algorithms. Beyond traditional risk factors such as age, body mass index and preexisting conditions, the team also focused on biochemical enzymes, as well as patients' levels of lipid metabolites.
Using the same machine learning methods, the researchers developed a decision tree to predict COVID-19 mortality. Most healthy individuals have circulating levels of the sPLA2-IIA enzyme hovering around half a nanogram per milliliter. According to the study, COVID-19 was lethal in 63% of patients who had severe COVID-19 and levels of sPLA2-IIA equal to or greater than 10 nanograms per milliliter.
"Many patients who died from COVID-19 had some of the highest levels of this enzyme that have ever been reported," said Chilton, who has been studying the enzyme for over three decades.
Previous research has shown how the enzyme destroys microbial cell membranes in bacterial infections, as well as its similar genetic ancestry with a key enzyme found in snake venom.
The protein "shares a high sequence homology to the active enzyme in rattlesnake venom and, like venom coursing through the body, it has the capacity to bind to receptors at neuromuscular junctions and potentially disable the function of these muscles," Chilton said.
"Roughly a third of people develop long COVID, and many of them were active individuals who now can't walk 100 yards. The question we are investigating now is: If this enzyme is still relatively high and active, could it be responsible for part of the long COVID outcomes that we're seeing?"
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