Heart, other organs show mitochondrial damage after COVID-19 despite recovery of lungs
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Key takeaways:
- Downregulation of mitochondrial genes in the heart and other organs persists after recovery from SARS-CoV-2 infection.
- These findings indicate COVID-19 may be “a systemic disorder that impacts multiple organs.”
Following SARS-CoV-2 infection, mitochondrial function remained impaired in the heart, liver and kidneys, despite observed recovery in the lungs, according to a human autopsy and animal tissue study.
“Upon SARS-CoV-2 infection of host cells, the viral copy number increases unchecked until the innate immune system is engaged, after which the viral copies progressively decline until the virus is eliminated,” Joseph Guarnieri, PhD, postdoctoral research fellow at the Center for Mitochondrial and Epigenomic Medicine at Children’s Hospital of Philadelphia, and colleagues wrote.
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Therefore, by quantifying SARS-CoV-2 RNA copies, the researchers evaluated human and rodent SARS-CoV-2 datasets representing the full course of SARS-CoV-2 infection progression.
“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,” Guarnieri said in a press release.
For the present study, Guarnieri and colleagues analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with COVID-19 as well as monitor bioenergetic change among early-infection hamsters and mid-infection mice.
The findings were published in Science Translational Medicine.
In human nasopharyngeal samples, SARS-CoV-2 virus blocked the transcription of certain nuclear DNA-encoded mitochondrial oxidative phosphorylation polypeptides; induced microRNA 2392 expression; activated hypoxia inducing factor-1 to induce glycolysis; and activated host immune defenses including integrated stress response, according to the study.
In human autopsy tissue from patients with COVID-19, SARS-CoV-2 virus was no longer present and mitochondrial gene transcription recovered in the lungs; however, nuclear DNA mitochondrial gene expression remained suppressed in heart tissue. Mitochondrial gene expression also remained lower in the kidney and liver, but to a lesser extent, according to the study.
Moreover, mitochondrial DNA transcription was induced in the studied autopsy tissue and host-immune defense pathways were activated, the researchers reported.
In infected hamsters with peak lung viral load, mitochondrial gene expression in the lung was not greatly affected but was downregulated in the cerebellum and upregulated in the striatum despite no virus detected in the brain.
In mid-infection of mice, mitochondrial gene expression had starting to recover in the lungs.
“These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses,” the researchers wrote.
“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,” Douglas C. Wallace, PhD, director of the Center for Mitochondrial and Epigenomic Medicine at CHOP, said in the release. “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.”
Reference:
- Researchers find COVID-19 causes mitochondrial dysfunction in heart and other organs. https://www.eurekalert.org/news-releases/997898. Published Aug. 9, 2023. Accessed Aug. 9, 2023.
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