Post by Nadica (She/Her) on Nov 22, 2024 3:00:14 GMT
SARS-CoV-2 can damage mitochondrion in heart, other organs, study finds - Published August 9, 2023
By Mary Van Beusekom, MS
The COVID-19 International Research Team (COV-IRT) and the Children's Hospital of Philadelphia (CHOP) report that they have identified abnormal mitochondrial function in the heart, kidneys, and liver after SARS-CoV-2 infection, which leads to long-term damage and may help explain long COVID.
Mitochondria are the so-called "powerhouses" of cells, and the researchers noted that previous studies have shown that SARS-CoV-2 proteins can bind to mitochondrial proteins in host cells, possibly leading to dysregulation.
The team analyzed mitochondrial gene expression in tissues from COVID-19 patients' nose and throat, along with tissues from deceased patients and hamsters and mice. The results were published today in Science Translational Medicine.
"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," first author Joseph Guarnieri, PhD, a postdoctoral research at CHOP, said in a hospital news release.
Research identifies potential therapeutic target
In autopsy tissue, mitochondrial gene expression had recovered in the lungs, but not in the heart, kidneys, and liver. The rodent tissue and measurement of the time of peak viral load in the lungs showed that mitochondrial gene expression was suppressed in the cerebellum, even though SARS-CoV-2 wasn't found in the brain. The cerebellum coordinates and regulates muscle activity.
Other animal models showed signs of recovery of mitochondrial function in the lungs during the mid-phase of COVID-19 infection.
Co-senior author Douglas Wallace, PhD, of CHOP, said that the study offers strong evidence that COVID-19 is a systemic disease that affects multiple organs rather than strictly an upper respiratory illness. "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," he said in the release.
The results also identified a potential therapeutic target, microRNA 2392, which was shown to regulate mitochondrial function in the human tissue samples, said co-senior author Afshin Beheshti, PhD, president of COV-IRT and a visiting researcher at the Broad Institute.
"This microRNA was upregulated in the blood of patients infected by SARS-CoV-2, which is not something we normally would expect to see," he said. "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."
The researchers said they will use these data to conduct future studies on how systemic immune and inflammatory responses may lead to more severe illness in some patients.
Study link: www.science.org/doi/10.1126/scitranslmed.abq1533
By Mary Van Beusekom, MS
The COVID-19 International Research Team (COV-IRT) and the Children's Hospital of Philadelphia (CHOP) report that they have identified abnormal mitochondrial function in the heart, kidneys, and liver after SARS-CoV-2 infection, which leads to long-term damage and may help explain long COVID.
Mitochondria are the so-called "powerhouses" of cells, and the researchers noted that previous studies have shown that SARS-CoV-2 proteins can bind to mitochondrial proteins in host cells, possibly leading to dysregulation.
The team analyzed mitochondrial gene expression in tissues from COVID-19 patients' nose and throat, along with tissues from deceased patients and hamsters and mice. The results were published today in Science Translational Medicine.
"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," first author Joseph Guarnieri, PhD, a postdoctoral research at CHOP, said in a hospital news release.
Research identifies potential therapeutic target
In autopsy tissue, mitochondrial gene expression had recovered in the lungs, but not in the heart, kidneys, and liver. The rodent tissue and measurement of the time of peak viral load in the lungs showed that mitochondrial gene expression was suppressed in the cerebellum, even though SARS-CoV-2 wasn't found in the brain. The cerebellum coordinates and regulates muscle activity.
Other animal models showed signs of recovery of mitochondrial function in the lungs during the mid-phase of COVID-19 infection.
Co-senior author Douglas Wallace, PhD, of CHOP, said that the study offers strong evidence that COVID-19 is a systemic disease that affects multiple organs rather than strictly an upper respiratory illness. "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," he said in the release.
The results also identified a potential therapeutic target, microRNA 2392, which was shown to regulate mitochondrial function in the human tissue samples, said co-senior author Afshin Beheshti, PhD, president of COV-IRT and a visiting researcher at the Broad Institute.
"This microRNA was upregulated in the blood of patients infected by SARS-CoV-2, which is not something we normally would expect to see," he said. "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."
The researchers said they will use these data to conduct future studies on how systemic immune and inflammatory responses may lead to more severe illness in some patients.
Study link: www.science.org/doi/10.1126/scitranslmed.abq1533