COVID-19 suppresses mitochondrial gene activity in heart, kidneys and liver

Mitochondrial genes in the heart, kidney, liver, and lymph nodes are downregulated following COVID-19, findings in humans and mice have shown.

Mitochondria are organelles found in most cells in the body and provide energy for cellular processes. Mitochondrial DNA is located in the mitochondria, and is separate from the nuclear DNA that exists in the cell's nucleus, though expression of genes from both interact. Now a study published in the journal Science Translational Medicine led by the Children's Hospital of Philadelphia and the COVID-19-International Research Team (COV-IRT) has demonstrated a process by which SARS-CoV-2 infection, the virus that causes COVID-19, results in down-regulation of some mitochondrial genes involved in energy production after infection in the lungs is resolved.

'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. 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.' said Professor Douglas Wallace, director of the Centre for Mitochondrial and Epigenomic Medicine at the Children's Hospital of Philadelphia.

Researchers analysed mitochondrial gene expression in tissue taken from deep inside the nose of live patients infected with SARS-CoV-2, as well as heart, kidney, liver, lymph nodes and lung tissue from patients who had died of COVID-19. This highlighted the change in mitochondrial gene expression through the different phases of infection and post-infection.

Data from the autopsy tissue showed mitochondrial gene suppression in the lungs returned to normal when the infection resolved; however, it remained downregulated in the heart and also in the kidneys and liver to a lesser extent. This data was supported by observations in mice and hamsters.

There is hope that these findings may aid in developing treatments for those diagnosed with long COVID, the term given to an array of symptoms, many associated with some of the organs listed in this study, that affect people for at least 12 weeks after they had COVID-19.

'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.' said Professor Wallace.