Is Long Covid a Mitochondrial Disease?

May 25, 2023

A paper published this month in the International Journal of Molecular Sciences outlines the increasing evidence that Long Covid may be caused by mitochondrial dysfunction.

Exhaustion and/or weakness exacerbated by exercise is a well-known Long Covid symptom and mirrors symptoms experienced by patients with Chronic fatigue or genetic mitochondrial diseases. In addition, comorbidities associated with serious illness from a Covid-19 infection such as diabetes, liver disease, and obesity are often metabolic, having a mitochondrial component. The neurological symptoms of Long Covid have been associated with both SARS-CoV-2 proteins and abnormal mitochondrial proteins in nerve cells. This evidence all points to mitochondrial involvement during both acute infection and Long Covid.

Mitochondria can be directly and indirectly affected by the SARS-CoV-2 virus. Recent studies have shown that the SARS-CoV-2 virus targets mitochondria and can be housed within the mitochondrial matrix (the innermost compartment of the mitochondria containing enzymes needed for cellular energy production). This not only damages the mitochondrial membranes and impairs their function but down-regulates (the process by which a cell decreases the quantity of a cellular component in response to an external stimulus) genes related to them. The virus has also been found to affect cell signaling via calcium channels. Infected cells often have elevated levels of calcium which negatively affects mitochondria. Because mitochondria are not only involved with cellular metabolism but also the immune response, the net effect is cellular metabolic dysfunction, cell death, and runaway inflammation. 

The hope with these findings is that drugs that both reduce viral load and support mitochondrial health will help Long Covid patients. The authors suggest a number of antioxidants and existing medications as targets for further research, including mPTP inhibitors, IL-6R and IL-1 receptor blockers, and MCU inhibitors.