Long COVID

By Ramsay Lewis & Dr. Yuhong Dong

One of the most devastating aspects of COVID-19 is that it can continue to affect patients for months—and even years—after infection.

Ask Carrie Anna McGinn. After a year of fighting off symptoms, Maclean’s Magazine reports that she continues to battle a cough, cognitive dysfunction, and pain.

While most patients successfully fight off the symptoms of COVID-19 within a few days, some continue to experience symptoms long after infection. When symptoms last longer than two months, persistent symptoms are diagnosed as post-COVID condition, also called long COVID.

But one aspect of long COVID that’s still developing is its pathophysiology—the why behind how long COVID symptoms occur. This may actually be the most interesting piece: What’s COVID-19 doing to the body that makes symptoms last for months or years?

Long COVID Could Be Caused by a Persistent Inflammatory Response

You might not realize how serious inflammation can be.

Inflammation is a natural bodily response when something goes wrong in the body. Basically, your body sends white blood cells, cytokines, and other immune cells to try to fight off infection or repair tissue. When those cells take effect, they start to repair tissue and get rid of toxins.

It’s this “fight” between your body’s protective cells and the harmful ones that causes inflammation.

Acute inflammation lasts just a little while. For example, imagine you twist your ankle. Your body sends out repair cells to the area. As the tissue is being repaired, there’s some inflammation in the ankle. Once the tissue is repaired, the inflammation dissipates.

Chronic inflammation happens when an inflammatory response lasts for a long time. It occurs because the cytokines and white blood cells, which contribute to inflammation, don’t dissipate. When inflammation becomes chronic, white blood cells can end up attacking both bad cells and good, healthy cells from your own body. It’s kind of like “friendly fire.”

One theory of long COVID is that it causes a kind of chronic inflammatory response. That inflammation is then partly responsible for a person’s ongoing symptoms.

Autoimmune Responses May Contribute to Long COVID

The body’s immune system is set up to protect itself against infections. But sometimes, immune cells mistakenly begin targeting the body itself instead of infections. That’s called an autoimmune response.

Allergic reactions are autoimmune responses. Autoimmune responses are also behind a number of other conditions, including lupus and rheumatoid arthritis.

Autoimmune responses are actually common after viral infections. It happens when some of the proteins of the virus resemble the proteins in normal human cells. The resemblance makes it easy for immune cells to get “confused” between the virus and the body’s own cells. This is what some believe hap-

The pathophysiology of why COVID symptoms can persist for months, or even years, is still developing.

pens with long COVID: The COVID-19 virus may trigger an autoimmune response and that response may be responsible for the long-lasting symptoms of long COVID.

Autoantibodies are proteins in your immune system that mistakenly target your body’s own tissues. Autoantibodies can be caused by a number of viruses, including Epstein-Barr virus, herpes virus 6, hepatitis A and C, and rubella virus.

So one possibility is that SARSCoV-2, the COVID-19 virus, also creates autoantibodies. Those autoantibodies, in turn, may continue to plague the body long after the virus itself is gone.

Long COVID May Be Caused by Hidden Reservoirs of the Virus in the Body

A third theory for the cause of long COVID is that the virus was never properly eliminated from the body in the first place. In other words, there’s a “reservoir” of the virus that continues to cause symptoms long after most people are back to normal.

There are a few pieces of evidence for this theory.

Some research has also found that while SARS-CoV-2 replicates in the lungs, nose, and throat, it can also replicate in cells in the small intestine. Multiple studies have reported that SARS-CoV-2 viral RNA has been detected in stool samples even after the virus is cleared from the nasopharynx.

Viruses can also find their way into the brain and live there relatively safely. Part of the reason for that is that the brain isn’t as easily accessed by the immune cells that would fight off the virus. Some research has found SARSCoV-2 in brain tissue—it may be that it’s able to live there and continue to cause symptoms.

Another piece of evidence for virus reservoirs is that the immune cells continue to adapt and become more potent over time in individuals with long COVID. This continual mutation of the immune cells is consistent with the persistence of an antigen.

Damaged Mitochondria

Mitochondria are little organs within tissue cells. They’re commonly referred to as the “powerhouse” of cells because their main job is to produce energy. Most cells in our body have mitochondria, but cells that require more energy—such as those in the retina, heart, muscles, and brain—have substantially more mitochondria.

Since mitochondria are so important to providing cells with energy, damaging them may help explain symptoms such as fatigue, muscle weakness, and some of the mental deficits such as brain fog.

MAIN THEORIES FOR LONG COVID

1. The virus causes chronic inflammatory response. 2. The virus triggers an autoimmune response. 3. The virus was never properly eliminated from the body in the first place. 4. The virus damages mitochondria.

When inflammation becomes chronic, white blood cells can end up attacking both bad cells and good, healthy cells from your own body. It’s kind of like ‘friendly fire.’