Dissecting a molecular mechanism for severe and lethal COVID-19

precision wellness graphic featuring Dr. SKi
On April 19, Dr. Floyd “Ski” Chilton discussed differences in COVID-19 disease severity as part of the Precision Wellness in the Time of COVID-19 series.
Dr. Brittany Uhlorn, BIO5 Institute

Though the United States only accounts for 4.25% of the world’s population, 20% of COVID-related deaths have been attributed to our country to date. 

While most COVID-19 cases are either asymptomatic or mild, it’s not very well understood why some individuals succumb to severe or lethal disease. During the Precision Wellness in the Time of COVID-19 seminar on April 19, Dr. Floyd “Ski” Chilton shed light on the molecular basis behind differences in disease severity. 

“To answer a question so complex like this one requires a transdisciplinary team of researchers,” said Chilton, Director of The Precision Nutrition & Wellness Initiative (PNWI) at the BIO5 Institute. “The transdisciplinary approach at BIO5 is one of the themes that originally attracted me to the University of Arizona.”

Ski Chilton smiling
Dr. Ski Chilton


Chilton and his multifaceted team analyzed blood samples from 127 patients at Stony Brook Medical Center in New York for cellular differences. These patients either tested negative for COVID-19 or had mild, severe, or lethal disease. 

By comparing metabolic and lipid (fat) differences between samples, the team aimed to identify a molecular signature or biomarker(s) associated with disease severity and death. With this information, researchers could better understand of the root cause of severe and lethal COVID-19 cases.

Results revealed two major trends: First, deceased patients had elevated markers of mitochondrial dysfunction. Mitochondria, the “powerhouse” of the cell, produce much of the energy necessary for our cells and organs to work optimally. Impaired function of these critical structures most likely leads to the failure of multiple organs seen in patients with severe disease.

Secondly, Chilton explained he and his team found high levels of phospholipase A2 (PLA2) in the blood of deceased patients compared to the other groups. PLA2 is an enzyme that cleaves fatty acids often found in cellular membranes – the semi-permeable structures that encase our cells. PLA2 is evolutionarily important for recognizing and destroying bacterial cell walls, but when overactive, can destroy our own cells, leading to tissue and organ damage. 

When released into the blood, PLA2 can also lead to mitochondrial dysfunction, as mitochondria evolved from bacteria more than one billion years ago. Further, enzyme overactivity can lead to white blood cell activation, ultimately triggering the late inflammatory responses that are seen in patients with severe and lethal COVID-19. 

According to Chilton, overactive and overabundant PLA2 can overshoot an individual’s “fitness threshold,” burdening them with a “freight train of inflammation” that impairs the ability of the body to effectivity manage the disease. Though it’s not well understood why some have more PLA2 activity than others, age may be a factor. 

Chilton is hopeful his research will not only provide an answer to why some patients develop severe and lethal disease while others don’t, but that it will also provide a target for COVID-19 treatment. 

Chilton’s lecture is part of a five-symposia series hosted by the BIO5 Institute and The Precision Nutrition & Wellness Initiative (PNWI). Please visit the PNWI website to learn more and register for upcoming talks. 

About the University of Arizona BIO5 Institute
The BIO5 Institute at the University of Arizona connects and mobilizes top researchers in agriculture, engineering, biomedicine, pharmacy, basic science, and computational science to find creative solutions to humanity’s most pressing health and environmental challenges. Since 2001, this interdisciplinary approach has been an international model of how to conduct collaborative research, and has resulted in disease prevention strategies, promising new therapies, innovative diagnostics and devices, and improved food crops.