- A new study concludes that increased levels of an enzyme called secreted phospholipase A2 group IIA (sPLA2-IIA) can predict mortality from severe COVID-19.
- The body produces sPLA2-IIA to help defend against bacterial infections, but high levels can cause organ damage.
- In the study, levels of the enzyme were approximately 10 times higher in people who died from COVID-19 than in people with a mild form of the disease.
- More research is needed to see whether these enzyme levels could be used to identify patients at risk of dying from COVID-19 — and whether sPLA2-IIA inhibitors might reduce mortality.
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COVID-19 is caused by a SARS-CoV-2 infection, and a person with the disease may or may not experience symptoms. Most people with
However, some people become severely ill, and older adults and people with
Some researchers originally proposed that severe COVID-19 could result from an overactive inflammatory response called cytokine storm syndrome.
But as the authors of the current investigation note, “More recent studies show that persistent [cytokine storm syndrome] is uncommon (
Pinpointing the underlying mechanism responsible for fatal COVID-19 is important, as it will help researchers and clinicians identify people most at risk of dying from the disease and develop effective treatments.
This prompted scientists from the University of Arizona, the Wake Forest University School of Medicine, and Stony Brook University to collaborate on the present study.
Their findings appear in The Journal of Clinical Investigation.
Senior study author Floyd “Ski” Chilton, Ph.D., a professor at the University of Arizona’s Department of Nutritional Sciences and the director of The Precision Nutrition and Wellness Initiative, told Medical News Today about the preliminary data that led to the hypothesis behind the study.
He explained that the team used
“High-resolution statistics and machine learning [identified] two processes that were associated with death,” he added. The two processes of note involved sPLA2-IIA and mitochondrial dysfunction.
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Notably, sPLA2-IIA levels increase significantly in people who have systemic inflammation, due to conditions such as
Prof. Chilton observed that sPLA2-IIA “shreds membranes,” explaining that it has “the biology that could cause multiple organ failure.”
He and his team examined stored blood plasma samples from 127 hospitalized patients between May and July 2020 for levels of lipid metabolites and other biochemical substances to identify patterns associated with mortality from COVID-19.
Ninety samples came from patients with either mild or severe COVID-19 or who had died from the disease, and 37 samples were from people who did not have COVID-19.
The mean ages differed among the groups with COVID-19. The youngest average age, of about 53, was in the mild group, and the oldest average age, of about 71, was in the deceased group.
The study included approximately the same number of male and female patients, and most were white. Baseline health conditions were similar across the groups, except for a higher incidence of rheumatologic disease in the non-COVID-19 patients.
The study found that people who had died from COVID-19 had sPLA2-IIA levels that were approximately 10 times higher than patients with mild disease and five times higher than patients who had survived severe COVID-19.
An sPLA2-IIA level of at least 10 nanograms per milliliter accurately predicted death from COVID-19 in 63% of patients in the study.
Further analyses identified that combined sPLA2-IIA and blood urea nitrogen levels predicted mortality better than either level individually. The researchers confirmed these results in an independent group of 154 patients.
Prof. Chilton said that the unbiased approach used to arrive at a hypothesis was a strength of the study. He elaborated:
“We then tested that hypothesis against 81 other clinical indicators, utilizing three separate machine learning models, and each of the three models said that this was the key step toward mortality.”
Limitations of the study include its small size and predominantly white population, limiting the generalizability of its results. It is also important to note that the study design does not prove causality.
Prof. Chilton went on to describe further research. “We’re working with other biorepositories, other institutions, [and] a large global institution to [look] at the temporal [and] the longitudinal relationship as the disease occurs, who dies, and the levels of this enzyme in those people.”
Scientists have already tested drugs that reduce the activity of sPLA2-IIA in phase 2B clinical trials. This was to investigate their potential as a treatment for sepsis, but the Food and Drug Administration (FDA) did not issue an approval.
Now, scientists may revisit these drugs as potential treatments for COVID-19. Prof. Chilton explained:
“There is great potential to take a drug that’s [been] through phase 2B clinical trials and [test for safety and efficacy in patients with] COVID-19 with the stratification strategies” of the research.
Dr. Shahyar Yadegar, a critical care and pulmonology specialist, and the medical director of the intensive care unit at the Providence Cedars-Sinai Tarzana Medical Center, who was not involved in the study, commented on the findings for MNT:
“The findings are promising for determining methods in predicting and standardizing patient risk for COVID-19 mortality. […] We know that inflammation plays a key role in a subset of patients that develop severe COVID-19, and if given the ability to predict hallmarks of these patients before their deterioration, therapies can be initiated to help best serve the patient.”