Kelly LaDue, 54, was working as a nurse when she contracted COVID-19 in the fall of 2020. After an acute illness that lasted a couple of weeks, she seemed to recover, but the recovery didn’t last long. Suddenly, she said, “I started with really bad heart-racing with any exertion. Walking up the stairs, I’d have to sit down and rest. And I was short of breath. I had to rest after everything I did. It was weird.”

A year later, LaDue still suffers from severe headaches, phantom smells, vibrations in her legs, and a high-pitched whistling in her ears. More often than not, she wakes up with pain throughout her body. Her brain fog got so bad that she quit her job and is afraid to drive. “These symptoms–they come and go,” she said. “You think, ‘It’s gone.’ You think, ‘This is it. I’m getting better.’ And then it’ll just rear back up again.”

Theories 

Some experts say that there’s reason to think that various symptoms have different causes in different patients. One theory is that the virus doesn’t always completely clear the system, and remains in hiding in certain organs or other reservoirs in the body, wreaking havoc when undetected. 

An offshoot of that theory is that the ongoing presence of the virus maintains a heightened level of immune-system activity, and the resulting stress on the body leads to the symptoms. Still, others think that the virus does leave the body, but that damage already done to the immune system may cause autoimmune responses. These are just a few theories currently on the table.

While there is a list of widely-reported symptoms common to COVID long-haulers, there are many factors that can influence how the syndrome manifests in each individual and how long it persists. “It’s still early days,” says Akiko Iwasaki, a professor of immunobiology at Yale University. “But we believe that long COVID is not caused by one thing. That there are multiple diseases that are happening.” 

New Clues

Researchers like Iwasaki have been finding some intriguing clues that may help solve the mystery of long COVID. Two clues are unusual levels of cytokines (chemical messengers used by the immune system) and autoantibodies (proteins that attack the body’s own cells and tissues instead of the virus) in the blood of some patients. “We’re trying to decode what those cytokines mean,” Iwasaki said. 

Dr. Steven Deeks at the University of California, San Francisco, has found elevated levels of a cytokine called interleukin-6 in his long-COVID patients, suggesting a state of chronic inflammation. “The first couple of weeks of the infection is associated with a massive amount of inflammation,” he said. “The virus just blows up the immune system, so it’s reasonable to think that, in some people…that can contribute to long COVID over time.”

An unusual activity pattern by key immune system cells such as T-cells also seem to be affecting a particular subgroup of patients, supporting the theory that the virus may linger while hiding in the body. According to Dr. Igor Koralnik at Northwestern Feinberg School of Medicine, “That’s a signature…which could be consistent with a low-level, but persistent, infection.” 

New Treatment Possibilities

While much more research is needed, the researchers hope these findings could eventually lead to ways to help long-COVID patients. One possible therapy for some patients might turn out to be antiviral drugs that target a virus hiding in the body. Another possibility might be clearing the virus with a vaccine, which does seem to help some long-COVID patients. 

Researchers think drugs that dampen down the immune system may also help.

“We need to understand what’s going on in each patient — because the treatment option will be very different depending on what they actually have,” Iwasaki says.

The Challenge of Finding Answers

One of the biggest challenges in the frantic search for causes and treatments is the persistent lack of medical evidence that anything is amiss. In the year and a half that he has been seeing long-COVID patients, said Dr. Michael Sneller of the National Institutes of Health, his team is finding few abnormalities. “Echocardiogram, pulmonary function tests, X-rays, brain MRIs…Laboratory markers of organ dysfunction. We’re not seeing any of that,” he said of the patients in his study. “I’m running out of tests to do, basically.”

Still, Sneller says his team hasn’t ruled anything out. It continues to analyze immune system data and is also conducting psychological tests on participants, but not because he doubts their stories. “It’s 100% real,” he insisted. “These people have these symptoms. Absolutely. The question is what’s causing them. Anxiety can produce real symptoms.”

In the meantime, researchers, doctors, and patients like Kelly LaDue all continue to seek answers and to hope that effective treatments are on the way. Like most long-COVID patients, LaDue just wants “to feel normal…The hardest part,” she says, “is trying to look and be normal, but not feeling normal.”

*Stein, R. (2021, Nov. 12). New Clues to the Biology of Long COVID Are Starting to Emerge. NPR.   https://www.npr.org/sections/health-shots/2021/11/12/1053509795/long-covid-causes-treatment-clues

Much about the novel coronavirus, i.e., COVID-19, is still not fully understood. As research progresses and our knowledge of the virus increases, information can change rapidly. We strive to update all of our articles as quickly as possible, but there may occasionally be some lag between scientific developments and our revisions.