New clues to the biology of long COVID are starting to emerge

We are beginning to see new clues about the biology of COVID.
Kelly LaDue toggle caption

After being afflicted by the virus for several weeks, Kelly LaDue believed she was over COVID-19 in fall 2020.

"And then, I started with really terrible heart-racing with any exertion. It was strange," LaDue, 54 of Ontario, N.Y., said. "Walking up stairs, I'd need to sit down and rest. And I was short-tempered. After everything I did, I needed to take a break."

LaDue still feels like an absolute wreck a year later. On more days than not, she wakes up with severe headaches and pain all over her body. A sudden, high-pitched whistling sound in her ears, strange phantom smells and vibrations in the legs are some of her other symptoms. She is afraid to drive and her brain is foggy.

She says, "These symptoms, these come and go." You think, 'It's gone. You think, 'It's gone.' I'm getting better.' It'll then just rearrange itself again."

Researchers are trying to find out why people with SARS-CoV-2 experience persistent and often debilitating symptoms like LaDue. It is not known how often this happens. It's important to note that COVID-19 is not a common condition.

Dr. Angela Cheung at the University of Toronto studies long-COVID. She believes it to be the post-pandemic epidemic. "If we assume that COVID-19 will affect only 10% of patients, then that's quite a large number.

"Not caused one thing"

There are many theories, but no clear answers. It is possible that the different symptoms may have different causes. Perhaps the virus is still present in the body, in some way, causing nerve damage or other problems. The virus may be present in the body for a long time, or perhaps remnants, which can cause symptoms. Perhaps the virus has passed, but the immune system isn't working properly, and it's attacking the body. Maybe there is another reason.

It's still early days. We believe that long COVID can be caused by more than one thing. "That there are multiple diseases that have been occurring," Akiko Iwasaki, Yale University professor of immunobiology, who is also researching long COVID.

Iwasaki and others began to find some intriguing clues in blood samples of patients. These include abnormal levels of cytokines (chemical messengers the immune system uses to communicate) and autoantibodies proteins, which attack cells and tissues of the body instead.

"We're seeing elevated levels of cytokines among long-COVID patients. We're trying to figure out what those cytokines are. Iwasaki also says that we are seeing a distinct auto-antibody reaction. We are trying to determine what these antibodies are doing and if they are causing any harm."

Similar findings have been made by other researchers. Steven Deeks, University of California San Francisco, discovered that long-COVID patients have elevated levels of interleukin-6. This suggests they might be suffering from chronic inflammation.

"The infection causes a lot of inflammation in the first few weeks. Deeks states that the virus "just blows up your immune system." "So, it is reasonable to believe that in some cases, acute COVID can cause an inflammatory condition that can lead to long-term COVID."

Another clue was found in a subgroup of patients. It is an unusual pattern in activity by key immune systems cells such as T-cells. This could support the theory that the virus may be hiding in the body.

Dr. Igor Koralnik, Northwestern Feinberg School of Medicine, says, "That's an indication or pattern that could be consistent with low-level, persistent infection in the long COVID syndrome patient."

Although more research is required, researchers believe these findings will eventually lead to new ways to help patients with long-term COVID. Anti-viral drugs, which target the virus hidden in the body, might be a possible treatment for some patients. A vaccine might also be an option to clear the virus. This may help long-COVID patients. Researchers believe drugs that lower the immune system might also be beneficial.

Iwasaki states, "We must understand the individual patient. Because their treatment options will differ depending on what they have."

There are still many questions that need to be answered

Others aren't convinced that the evidence linking subtle changes in laboratory tests to physical symptoms in long-COVID suffers is convincing. This includes any signs that the immune system may be the problem, also known as an autoimmune disease.

Dr. Michael Sneller has been performing detailed tests on hundreds of COVID patients at National Institutes of Health.

"Echocardiograms, pulmonary function tests and X-rays are all available. It's all there. There are many laboratory markers that indicate organ dysfunction. Sneller states that he is not seeing any evidence of organ dysfunction in the patients in his research. "And very little evidence of immune activation, just looking at the standard markers of inflammation. There are not enough tests for me to perform.

Sneller said that his team hasn’t ruled anything out and is still analyzing data about the immune system. Sneller's team is also performing psychological testing on the subjects of their study -- but not because he doubts their symptoms.

It's 100% true. These symptoms are common in these people. Yes. He says the question is "What's causing them?" Anxiety can cause real symptoms.

LaDue, for her part, hopes that researchers will eventually find out what is going on with her and the other patients.

She says, "I want to feel normal. I hope to be normal again someday." The hardest part is to try and look normal, but not feel normal.