Mitochondrial function in the lung showed recovery, but this was not the case in the heart and other organs. This lasting damage could be a potential explanation for the adverse effects associated with the “long-lasting novel coronavirus”.
from the beginning of COVID-19 (novel coronavirus infection) pandemic caused by SARS-CoV-2 virusScientists have been working to understand the unique long-term effects it has compared to other coronaviruses.
Now, a multi-institutional consortium of researchers led by the Children’s Hospital of Philadelphia (CHOP) and the International Covid-19 Research Team (COV-IRT) have found that the virus has negatively impacted the genes of our life force, the mitochondria. found that it could give Cell damage – leading to malfunction of several organs, not just the lungs.The survey results were published in a magazine scientific translational medicinepaving the way for new therapeutic strategies for COVID-19.
Mitochondria are present in every cell in our body. Genes involved in mitochondrial generation are dispersed within and within the nucleus. DNA Located in the nucleus of our cells, it is the mitochondrial DNA (mtDNA) located within each mitochondria. Previous studies have shown that SARS-CoV-2 proteins can bind to mitochondrial proteins in host cells and cause mitochondrial dysfunction.
To understand how SARS-CoV-2 affects mitochondria, researchers at CHOP’s Center for Mitochondrial and Epigenomic Medicine (CMEM), along with colleagues at COV-IRT, analyzed mitochondrial gene expression. and wanted to detect differences caused by viruses. To do this, they analyzed combined nasopharyngeal and autopsy tissue from diseased patients and animal models.
“By using tissue samples from human patients, we were able to explore how mitochondrial gene expression is affected at the beginning and end of disease progression. We were able to fill in the blanks and look at the progression of gene expression differences over time,” said Dr. Joseph Guarnieri, lead author of the study and postdoctoral fellow at CHOP’s CMEM.
This study found that mitochondrial gene expression was restored in lung, but mitochondrial function remained suppressed in heart, kidney, and liver in autopsy tissue. Studying an animal model and measuring the time to peak viral load in the lungs, mitochondrial gene expression was suppressed in the cerebellum, even though SARS-CoV-2 was not observed in the brain. Additional animal models revealed that lung mitochondrial function began to recover during the middle stages of SARS-CoV-2 infection.
Taken together, these results suggest that host cells respond to initial infection in a manner involving the lung, but over time mitochondrial function is restored in the lung, while mitochondrial function remains impaired in other organs, particularly the heart. It reveals that there is
“This study provides strong evidence that we need to stop looking at COVID-19 strictly as an upper respiratory disease and start looking at it as a systemic disease that affects multiple organs. said co-author Douglas C. Wallace, Ph.D. D., Director of CHOP CMEM. “The continued dysfunction observed in organs other than the lung suggests that mitochondrial dysfunction may be causing long-term damage to internal organs in these patients.”
Future studies using this data will explore how systemic immune and inflammatory responses play a role in more serious disease in some patients, but the researchers found that mitochondrial function We discovered a potential therapeutic target in microRNA 2392 (miR-2392), which was shown to regulate In the human tissue samples used in this study,
“This microRNA was upregulated in the blood of patients infected with SARS-CoV-2, something we would not normally expect to see,” said co-senior author and biostatistician. said Dr Afshin Beheshti, a biostatistician. Founder and President of the Broad Institute, COV-IRT. “Neutralizing this microRNA may interfere with viral replication, potentially providing an additional treatment option for patients at risk of more severe complications associated with this disease. there is.”
Earlier this year, the Gates Foundation asked Dr. Wallace and CMEM how variations in mtDNA among the global population affect mitochondrial function and, in turn, individual susceptibility to SARS-CoV-2. provided funding to study According to Wallace, the demonstration that SARS-CoV-2 has a pronounced effect on mitochondrial function supports the hypothesis that individual differences in mitochondrial function may be a factor in individual severity of COVID-19. It is a thing.
Reference: “Core mitochondrial genes are downregulated during SARS-CoV-2 infection of rodent and human hosts.” Joseph W. Guarnieri, Joseph M. Dybas, Hossein Fazelinia, Man S. Kim, Justin Frere, Yuanchao Zhang, Yentli Soto Albrecht, Deborah G. Murdoch, Alessia Angeline, Larry N. Singh, Scott L. Weiss, Sonya M. Best, Marie T. Lott, Siping Chan, Henry Cope, Victoria Sachsas, Amanda Saravia-Butler, Sem Meydan, Jonathan Fox, Christopher Mozary, Yaron Blum, Jared Kidan, Waldemar Prieve, Mark R. Emmett, Robert Meller, Sam Demherter, Valdemar Stentoft Hansen, Marco Salvatore, Diego Galeano, Francisco J. Enguita, Peter Grabham, Nidia S. Trovao, Urminder Singh, Jeffrey Haltom, Mark T. Heise, Nathaniel J. Moorman, Victoria K. Baxter, Emily A. Madden, Sharon A. Taft Benz, Elizabeth J. Anderson, Wes A. Saunders, Rebecca J. Dickmander, Stephen B. Balin, Eve Silkin Waterle, Pedro M. Moraes-Vieira, Dean Taylor, Christopher E. Mason, Jonathan C. Sisler, Robert E. Schwartz, Afshin Beheshti, Douglas C. Wallace, August 9, scientific translational medicine.
This work was also supported by the NIAID, the NIH Intramural Research Division, and in part by the Bill & Melinda Gates Foundation grant INV-046722.