The Long-Term Effects of SARS-CoV-2 on Mitochondria and Potential Treatments

The coronavirus SARS-CoV-2 disrupts the energy management of its host for a long time. It does this by thwarting the functioning of the energy factories in cells, the mitochondria. An extensive study in infected humans and laboratory animals reveals that this function is quickly restored in the lungs, but sometimes not in the heart and other organs. Scientists suspect that this could contribute to a serious course of Covid-19 and possibly also to the long-term complaints of lung covid.

The findings that published Wednesday Science Translational Medicineprovide starting points for new treatments.

This remains much needed, because the battle with the coronavirus, which is constantly escaping the immune system, continues. For several weeks now, a new variant, EG.5., has been gaining the upper hand in the United States and parts of Asia, and hospital admissions are on the rise again. The WHO holds next to this eight other variants in the eye.

Burning nutrients

Mitochondria are located in almost every cell in our body. They provide the energy to work and grow by burning nutrients, such as glucose. They store that energy in a molecule from which it is easy to use (ATP). A cell sometimes contains thousands of mitochondria. The largest numbers are found in organs that require a lot of energy, such as the heart, brain, liver and skeletal muscles.

Previous studies have already shown that the coronavirus binds to proteins in mitochondria. The new research shows that the virus intervenes even deeper: it also disrupts the production of various important metabolic proteins. Scientists suspect that the long-term effects of the virus on a variety of organs may be related to this – the new study reinforces that theory.

The researchers studied samples from the nose and throat of 700 people from New York, both infected and uninfected people. The more virus there was in the airways, the stronger the inhibition of the mitochondria in the lungs. This recovered again with decreasing amounts of virus.

However, this was not the case in other organs, as was found in laboratory animals and deceased patients. The scientists examined the hearts, kidneys, liver, lungs and lymph nodes of 35 people who had died of Covid-19 (and of five who died uninfected). In all tissues except the lungs, the genes for energy production were less active in this last stage of the disease.

Cause or effect

The findings are in line with previous studies that show disruptions in metabolism and in the function of mitochondria caused by the coronavirus, says research physician Brent Appelman, who studies lung covid at Amsterdam UMC. He worked on one recent Dutch study which showed that a metabolic enzyme, IDO-2, is much more active in white blood cells and in brain tissue of people with long-term covid. In the blood cells, this is accompanied by a reduced functioning of mitochondria. “But that does not yet show whether it is the cause of the complaints, or a consequence.”

Scientists are looking for ways to boost mitochondrial activity. The resources that are available don’t do much yet. “In addition, it is important to address the underlying cause of the malfunctioning mitochondria,” says Appelman. “Otherwise it has little effect, just like accelerating in a car while pressing the brake makes little sense. Our next step is to see if we can inhibit IDO-2 in patients with lung covid and thus improve mitochondrial function.”

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A version of this article also appeared in the August 10, 2023 newspaper.
2023-08-09 16:00:13
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