A new study has found that SARS-CoV-2, the virus that causes COVID-19, damages the genes of the mitochondria, the cell’s energy generators, causing dysfunction in organs other than the lungs that continues after the lungs have recovered. The finding may explain why some people suffer from long COVID.
Since the COVID-19 pandemic first hit, researchers have been trying to figure out why, compared to other coronaviruses, SARS-CoV-2 produces such negative long-term effects.
Long COVID is the condition where symptoms persist for weeks, months, and even years after infection with SARS-Cov-2. Chronic pain, brain fog, shortness of breath, chest pain and intense fatigue – all of which can be debilitating – are common long COVID symptoms. Now, a study led by researchers at the Children’s Hospital of Philadelphia (CHOP) and the COVID-19 International Research Team (COV-IRT) may have provided some answers. And it has to do with mitochondria, the powerhouses of cells.
Every cell has mitochondria, and each mitochondrion contains its own DNA (mitochondrial DNA or mtDNA). mtDNA contains 37 genes, 13 related to making enzymes for energy production, with the remaining genes providing instructions for making molecules called transfer RNA (tRNA) and ribosomal RNA (rRNA), the chemical cousins of DNA that help assemble amino acids into functioning proteins.
To analyze how SARS-CoV-2 impacts mitochondria, the researchers studied their gene expression using a combination of nasopharyngeal (nose and throat) and autopsy tissues from affected patients and animal models.
“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 Joseph Guarnieri, the study’s lead author.
They found that, in autopsy tissue, mitochondrial gene expression in the lungs had recovered, but mitochondrial function in the heart, kidneys and liver remained suppressed. In animal models where the virus had peaked in the lungs, the researchers found that mitochondrial gene expression was suppressed in the cerebellum even though SARS-CoV-2 was not seen in the brain. Additionally, animal models revealed that during the mid-phase of the infection, lung mitochondrial function was beginning to recover.
The findings suggest that while SARS-CoV-2 infection initially involves the lungs, over time, mitochondrial gene expression is restored there but remains impaired in other organs, the researchers say. They also say that the findings support the hypothesis that individual differences in mitochondrial function may explain why the severity of COVID1-9 infections differs between people.
“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 systematic disorder that impacts multiple organs,” said co-author Douglas Wallace. “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.”
The study did identify a potential therapeutic target, microRNA 2392 (miR-2392), which was shown to regulate mitochondrial function in human tissue samples analyzed by the researchers.
“The microRNA was upregulated in the blood of patients infected by SARS-CoV-2, which is not something we normally would expect to see,” said Afshin Beheshti, another of the study’s co-authors. “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 study was published in the journal Science Translational Medicine.
