While COVID primarily affects the respiratory system and lungs, a new study showed that the SARS-CoV-2 virus can alter mitochondria on a genetic level, leading to widespread “energy outages” throughout the body and major organs, finds a study.

The new findings, published in the journal Science Translational Medicine, explain how these effects contribute to long COVID symptoms and point to new therapeutic targets.

Every cell in our bodies is equipped with biological power stations known as mitochondria, which are especially important for maintaining the function of energy-demanding organs, such as the heart, brain, and lungs. 

Mitochondria require genes from their own genome (mitochondrial DNA) and nuclear DNA (nDNA) to create energy. Together, they instruct the mitochondria to convert oxygen molecules into cellular energy called adenosine triphosphate (ATP).

“We found that at peak infection time, there are distinct changes in different regions of the brain, including a large decrease in mitochondrial genes in the cerebellum, the part of the brain that controls our muscles, balance, cognition, and emotion,” said Jonathan C. Schisler, Assistant Professor of pharmacology at University of North Carolina’s School of Medicine. 

“The lung is the primary site of infection, but molecular signals are being transmitted affecting the entire body, with the heart, kidney, and liver being more affected than others, even long after the virus is gone,” he added. 

Using nasal swabs and autopsy tissues from affected patients and experimental models, researchers found that the virus blocks specific genes that use oxygen to create ATP, forcing the body to deplete finite energy reserves in the body. Without an energy source, cells throughout the body begin to starve, with the cells powering the brain and the heart suffering the most.

To keep the body functioning, cardiac and neural cells can resort to consuming their cellular parts, including their mitochondria. Eventually, the cells are deprived of their vital elements and initiate a form of programmed cell death called necroptosis. 

Unlike other forms of cellular death, necroptosis causes a cascade of ill effects, including a robust inflammatory response, which releases pro-inflammatory cells called cytokines throughout the body as the cells rupture. Uncontrolled necroptosis further enhances sepsis and organ failure.

Schisler said the ensuing cell death and inflammation may explain why patients with long COVID are likely to have persisting cardiovascular, cognitive, and inflammatory side effects after the initial infection has run its course.

The new findings also highlight new ways to address the mitochondrial dysfunction that occurs during COVID infection. Diet, exercise, natural compounds, or a combination of the three, may be able to stimulate mitochondrial function, but whether or not they are effective for patients with long COVID is yet to be known, the team said.