Rattlesnake neurotoxin linked enzyme linked to severity of COVID-19 infection

Study shows that an enzyme involved in the inflammatory response may be a key mechanism for the severity of COVID-19 and could provide a new therapeutic target.

Image Credit: Maria Dryfhout / Shutterstock.com

A single enzyme has been shown to be a primary predictor of the severity of COVID-19

Scientists at the University of Arizona, Stony Brook University, and Wake Forest University School of Medicine have reported that the group IIA enzyme phospholipase A2, called sPLA2-IIA, may be the factor most important for predicting which COVID-19 patients ultimately succumb to the virus.

The sPLA2-IIA enzyme is similar to that contained in rattlesnake neurotoxin in that it can destroy cell membranes and is usually found in low concentrations in healthy individuals as it is a key defense against bacterial infections.

At high levels, the activated enzyme can shred the membranes of vital organs, as described by Floyd Chilton, lead author of the article and director of the Precision Nutrition and Wellness Initiative at the University of Arizona:

It is a bell-shaped curve of disease resistance versus host tolerance. In other words, this enzyme tries to kill the virus, but at some point it is released in such high amounts that things go in a very wrong direction, destroying the patient’s cell membranes and thus contributing to malfunctions of the patient. ‘multiple organs and death. “

Chilton

To better understand the role of this enzyme and its role in the severity of COVID-19 infection, the researchers collected blood samples from patients to quantify the concentration of sPLA2-IIA.

The results can then be used to inform possible targets of preventive or post-infection treatments to avoid further mortality, but the recent increase in cases in the United States, especially variants of COVID-19, has increased levels. emergency in clinical settings.

Develop a diagnosis in a context of increasing urgency

Plasma samples and medical record information were first collected from 127 patients hospitalized at Stony Brook University between January and July 2020 by Del Poeta and his team. A second cohort then included data from 154 patients from StonyBrook and Banner University Medical Center in Tucson between January and November 2020.

Co-author Maurizio Del Poeta, Distinguished SUNY Professor in the Department of Microbiology and Immunology at the Renaissance School of Medicine at Stony Brook University, says:

“These are small cohorts, yes, but it was a heroic effort to obtain them and all the associated clinical parameters from each patient under these circumstances,” said Chilton. “Unlike most studies which are well planned over the years, this was happening in real time in the intensive care unit.”

Machine learning algorithms were then used to analyze patient data points taking into account age, body mass index and pre-existing conditions, as well as biochemical enzymes and lipid metabolite levels of patients. This array of variables goes beyond the traditional clinical trial as it also provides a biochemical profile of the patients to support the results.

This profile was then used to develop a predictive decision tree that can inform and predict the risk of COVID-19 mortality in patients with specific symptoms and characteristics.

In this study, we were able to identify patterns of metabolites that were present in individuals who succumbed to the disease. Metabolites that surfaced revealed dysfunction of cellular energy and elevated levels of the enzyme sPLA2-IIA. The first was expected but not the second. “

Justin Snider, Assistant Research Professor in the Department of Nutrition at the University of Arizona

sPLA2-IIA associated with high mortality from COVID-19: mechanism and implications.

Healthy individuals typically have sPLA2-IIA enzyme levels of around half a nanogram per milliliter (mL) of blood, but study results showed COVID-19 infection was fatal in 63% patients who had severe COVID-19 and sPLA2-IIA levels equal to or greater than 10 nanograms per ml of blood.

“Many patients who died from COVID-19 had some of the highest levels of this enzyme ever reported,” says Chilton.

This is of particular concern because the function of the sPLA2-IIA enzyme has been studied for half a century and it is “possibly the most examined member of the phospholipase family,” explained Chilton.

In previous studies, the enzyme has been shown to destroy microbial cell membranes in bacterial infections and share similar genetic ancestry with a key enzyme found in snake venom. Charles McCall, lead author of the study, describes the enzyme as a “shredder” for its effect in causing serious inflammatory events, such as bacterial sepsis, as well as hemorrhagic and cardiac shock.

The protein “shares high sequence homology with the active enzyme in rattlesnake venom and, like the venom that passes through the body, has the ability to bind to receptors at neuromuscular junctions and potentially deactivate the function of these. muscles, ”Chilton described.

About a third of people develop long-term COVID, and many of them were active people who can now no longer walk 100 meters. The question we’re currently investigating is: if this enzyme is still relatively high and active, could it be responsible for some of the long COVID results we’re seeing? “

Although the present study does not establish causal factors, further studies on how this particular enzyme is activated will provide valuable information for potential treatments.