Study Finds COVID-19 Causes Mitochondrial Dysfunction in Heart and Other Organs

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A recent study showed that COVID-19 can negatively impact the genes of mitochondria, which may lead to dysfunction in multiple organs, including the heart and lungs.

Published in Science Translation Medicine, the study was led by a team at the Children’s Hospital of Philadelphia (CHOP) and the COVID-19 International Research Team (COV-IRT). According to the study’s authors, the genes responsible for generating mitochondria, the cell’s energy producers, are spread throughout the nuclear DNA and the mitochondrial DNA (mtDNA). Prior investigations have shown that SARS-CoV-2 proteins can bind to mitochondrial proteins in host cells, which could lead to mitochondrial dysfunction. For this investigation, researchers aimed to better understand how SARS-CoV-2 impacts mitochondria. To do this, they analyzed mitochondrial gene expression in a combination of nasopharyngeal and autopsy tissues from patients and animal models infected with COVID-19. 

“The tissue samples from human patients allowed us to look at how mitochondrial gene expression was affected at the onset and end of disease progression, while animal models allowed us to fill in the blanks and look at the progression of gene expression differences over time,” said the study’s first author Joseph Guarnieri, PhD, a postdoctoral research fellow at the Center for Mitochondrial and Epigenomic Medicine (CMEM) at CHOP.

The study found that in the autopsy tissue, mitochondrial gene expression had recovered with time from the virus in the lungs; however, in the heart, kidneys, and liver, mitochondrial function remained suppressed. In the animal models, researchers discovered that when the viral load was at its peak in the lungs, mitochondrial gene expression was suppressed in the cerebellum, even though there was no detection of SARS-CoV-2 in the brain. Other animal models revealed that mitochondrial function in the lungs began to recover during the mid-phase of a COVID-19 infection.

According to the researchers, these results suggest that the virus initially impacts mitochondrial gene expression in the lungs. However, as time goes on, mitochondrial function is restored in the lungs while mitochondrial function in other organs, particularly the heart, remains impaired.

“This study provides us with strong evidence that we need to stop looking at COVID-19 as strictly an upper respiratory disease and start viewing it as a systemic disorder that impacts multiple organs,” said co-senior author Douglas Wallace, PhD, director of the CMEM at CHOP. “The continued dysfunction we observed in organs other than the lungs suggests that mitochondrial dysfunction could be causing long-term damage to the internal organs of these patients.”

Researchers also found a potential therapeutic target in microRNA 2392 (miR-2392), which was shown to regulate mitochondrial function in human tissue samples used in the study.

“This microRNA was upregulated in the blood of patients infected by SARS-CoV-2, which is not something we normally would expect to see,” said co-senior author Afshin Beheshti, PhD, a biostatistician, a visiting researcher at The Broad Institute, and founder and President of COV-IRT. “Neutralizing this microRNA might be able to impede the replication of the virus, providing an additional therapeutic option for patients who are at risk for more serious complications related to the disease.”

Future studies, researchers suggested, should use this data to better understand how the systemic immune and inflammatory response contributes to severe cases of COVID-19.