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.