2021-08-25

Such as venom flowing in the body: new research identifies the mechanism that causes COVID-19 mortality

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Such as venom flowing in the body: new research identifies the mechanism that causes COVID-19 mortality

Researchers from the University of Arizona collaborated with Stony Brook University and Wake Forest University School of Medicine to analyze two COVID-19 patients The blood samples of the cohort found the circulation of the phospholipase A2 group IIA (sPLA2-IIA) secreted by the enzyme. It is reported that sPLA2-IIA may be the most important factor predicting which severe COVID-19 patients will eventually die from the virus.

The low concentration of sPLA2-IIA found in healthy people is similar to an active enzyme in rattlesnake venom. It has long been known that it plays a key role in preventing bacterial infections and destroying microbial cell membranes. effect.

Floyd (Ski) Chilton pointed out that when active enzymes circulate at high levels, it has the ability to “tear” the membranes of vital organs. Floyd (Ski) Chilton is the senior author of this paper and the director of the Precision Nutrition and Health Program in the School of Agriculture and Life Sciences at the University of Arizona.

He continued: “This is a bell curve of disease resistance and host tolerance. In other words, this enzyme tries to kill the virus, but to a certain extent, its release Such a high level causes the disease to develop in a very bad direction, thereby destroying the patient’s cell membrane and causing multiple organ failure and death.”

The co-author of the research paper and the State University of New York, Stony Brook University Literary and Art Institute Maurizio Del Poeta, a distinguished professor of the Department of Microbiology and Immunology at Fuxing Medical College, said that together with the existing clinically tested sPLA2-IIA inhibitors, “this research supports a new treatment goal to reduce or even prevent deaths from COVID-19. Rate.”

Del Poeta said: “The idea of ​​identifying potential prognostic factors in COVID-19 patients originated from Dr. Chilton. He contacted us for the first time last fall and proposed to analyze blood samples from COVID-19 patients. The idea of ​​lipids and metabolites in China.”

Del Poeta and his team collected stored plasma samples and began to analyze medical charts, tracking the hospital stay in Stony Brook from January to July 2020 Key clinical data of 127 patients. The second independent cohort included 154 patient samples collected from Stony Brook and Banner University Medical Center in Tucson from January to November 2020.

Chilton said: “It is true that this is a small cohort, but in this case, it is a heroic effort to obtain them and all relevant clinical parameters from each patient. After years of carefully planned research, this is happening in real time at the ICU level.”

The research team was able to use machine learning algorithms to analyze thousands of patient data points. In addition to traditional risk factors such as age, body mass index, and past conditions, the team also focused on biochemical enzymes and the patient’s lipid metabolite levels.

“In this study, we were able to identify the patterns of metabolites in the human body who died of this disease,” the lead author of the study and an assistant research professor in the Department of Nutrition at the University of Arizona Justin Snider said, “The metabolites that surfaced revealed cellular energy disorders and high levels of the sPLA2-IIA enzyme. The former is expected, but the latter is not.”

By using the same With machine learning methods, researchers have developed a decision tree to predict the mortality rate of COVID-19. The level of the sPLA2-IIA enzyme in the blood of most healthy people hovers around half a nanogram per milliliter. According to this study, 63% of patients with severe COVID-19 and sPLA2-IIA levels equal to or greater than 10 ng/ml will die of COVID-19.

Chilton, who has studied this enzyme for more than 30 years, said: “Many patients who died of COVID-19 have the highest levels of this enzyme since reports.”

sPLA2 -The role of the IIA enzyme has been studied for half a century, and it “may be the most studied member of the phospholipase family,” Chilton said.

Charles McCall, the lead researcher of this study from Wake Forest University, called this enzyme a “pulverizer” because it is known to be involved in severe inflammatory events such as bacterial sepsis, hemorrhagic and cardiac shock. Ubiquitous in.

Previous research has revealed how this enzyme destroys microbial cell membranes in bacterial infections and its genetic ancestor similar to a key enzyme found in snake venom.

Chilton pointed out that this protein “has a high degree of sequence homology with the active enzymes in rattlesnake venom, just like the venom flowing through the body, it has the ability to bind to the receptors at the neuromuscular junction and possibly The function of these muscles is lost. About one-third of people have been infected with the new coronavirus for a long time. Many of them were active before and cannot walk 100 yards. The question we are now studying is: if this enzyme is still Relatively tall and active, will it be responsible for the long-term results of COVID that we are seeing?”