A New Study Finds a Link Between Long-Haul COVID Symptoms and Mitochondria Damage

As the pandemic continues, long COVID-19 remains very prevalent (affecting between 31 and 69 percent of COVID-19 patients) and somewhat bewildering, because there’s no clear connection between the severity of a patient’s initial symptoms and how long they might linger. That was one thing that Irina Petrache, MD, chief of the Division of Pulmonary at National Jewish Health in Denver, noticed early on in the pandemic. “As the first survivors of COVID emerged, it became clear that many of them suffered from prolonged illness,” Dr. Petrache tells POPSUGAR.

But when Dr. Petrache and her fellow researchers looked at 50 such patients at their hospital, they realised that “the vast majority of them did not have severe acute COVID,” she says. “They suffered from this acute viral infection at home, and they recovered without needing extra oxygen or needing to go to the hospital.”

Those 50 patients helped form the basis of a new preliminary study, coauthored by Dr. Petrache, that attempted to pinpoint the causes of long COVID. The researchers came away with a striking discovery: that the virus was damaging the mitochondria in the cells of long COVID patients. Mitochondria (as you might remember from high school biology) is a crucial organelle within the cell, tasked with turning oxygen and other nutrients into ATP, which is the energy that your muscles use to move and contract. Mitochondria are essentially “little factories in all our cells that produce energy,” Dr. Petrache says. When they’re not working properly, it’s a bad sign.

Exercise Study Found Connection Between Long COVID and Mitochondria

In the study, researchers asked patients to undergo cardiopulmonary exercise testing, which involved exercising on either a stationary bike or a treadmill and slowly increasing the resistance or incline to the point of fatigue. As they exercised, researchers recorded “massive amounts of data,” Dr. Petrache says, from heart rate and blood pressure to the amount of oxygen and carbon dioxide in their inhalations and exhalations. They also took arterial blood samples to measure carbon dioxide and lactate in the blood.

At first, the data didn’t seem to add up. The researchers saw that their patients were tiring more quickly than expected, but on the surface, their lungs, heart, and muscles seemed to function correctly. It wasn’t until they looked on the cellular level that they realised what was happening. The abnormally fast rate at which lactate (a byproduct substance produced during exercise) was rising, as well as clues from the gases that patients exhaled, suggested that the cause lay within the mitochondria.

“All these formulas and results pointed in the same direction: that there is something wrong with these little organelles,” Dr. Petrache says. “They’re just not working like they should be.”

How Does COVID-19 Affect Mitochondria?

Researchers don’t know the exact mechanism by which SARS-COV-2 (the virus that causes COVID-19) affects the mitochondria, though this is not the first study to point out a connection. One possibility is that, when the virus particles break into a cell, it causes a “cascade of events” that damages the mitochondria; specifically, Dr. Petrache says, the virus can lead to the release of a substance called angiotensin, which, when accumulated in this way, can “unlock” the mitochondria and damage it.

But Dr. Petrache notes that the pathway might be more indirect, as well; the virus might affect the flow of oxygen in the bloodstream, which then deprives the mitochondria of fuel. It might also affect the life cycle of mitochondria, causing premature death to the organelles or slowing the production of new mitochondria.

Finding the exact mechanism of the mitochondria dysfunction is one of the next steps Dr. Petrache hopes to take. “All these permutations or possibilities are subject to research now,” she said. “We really want to pinpoint it.” To do that, they hope to expand their study, bringing in more long COVID patients and adding a control group of people who recovered from their COVID-19 symptoms without a problem.

Additionally, though this test looked at muscle function in long COVID patients, the researchers believe the same process could be related to other long COVID symptoms, such as lung or neurological issues.

How Can Long COVID Patients “Fix” Their Mitochondria?

Dr. Petrache stresses that COVID-induced mitochondrial dysfunction needs to be studied in a controlled trial before potential treatments or interventions can be offered. However, she notes that a known intervention for mitochondrial issues is to “start low and go slow” with exercise, rather than abruptly leveling your exercise up or rushing through a fitness program. This slow and steady form exercise, also known as “Zone 2 exercise,” is known to improve mitochondria function, Dr. Petrache says. It could help in the case of long COVID as well.

In the long run, the hope is that this preliminary study will open the doors for more research into the connection between long COVID and mitochondria. Eventually, the goal is to find treatment options and a way forward for patients struggling with these symptoms.

“There was a lot of frustration that we saw in our [long COVID] patients,” Dr. Petrache said. “Now we can reassure them that once those classical diagnosis [like heart disease or lung disease] have been ruled out, if they are fatigued post-COVID, if they have shortness of breath . . . then this could be very well cause.”