Kelly LaDue thought she was done with COVID-19 in the fall of 2020 after a few miserable weeks of being tormented by the virus.
“And then I started having a really bad heart rate with every effort. It was weird,” says LaDue, 54, of Ontario, NY. “When I went up the stairs, I had to sit down and rest. And I was short of breath. I had to rest after everything I did.”
A year later, LaDue still feels like a wreck. She gets severe headaches and wakes up on several days with pain all over her body. She also experiences a sudden high-pitched whistle in her ears, bizarre ghost smells, and tremors in her legs. Her brain is usually so foggy that she has had to quit her job as a nurse and is afraid to drive.
“These symptoms, they come and go,” she says. “You think, ‘It’s gone.’ You think, “This is it. I’m getting better.” And then it just comes back.”
Patients like LaDue have researchers struggling to figure out why some people experience persistent, often debilitating symptoms after catching SARS-CoV-2. It remains unclear how often it occurs. But if only a small fraction of the hundreds of millions of people who have had COVID-19 struggle with long-term health problems, it is a major public health problem.
“I think it’s the post-pandemic pandemic,” said Dr Angela Cheung, a long-time student at the University of Toronto at the University of Toronto. “If we’re conservative and think that only 10% of patients who develop COVID-19 would get COVID-19 for a long time, that’s a huge number.”
“Not Caused by One Thing”
So far there are more theories than clear answers for what’s going on, and there’s good reason to believe that the varied constellation of symptoms could have different causes in different people. Perhaps the virus is still hiding somewhere in the body, in some, directly damaging nerves or other parts of the body. Perhaps the chronic presence of the virus, or remnants of the virus, keeps the immune system on hold, causing the symptoms. Maybe the virus is gone, but the immune system isn’t confused, so it’s now attacking the body. Or maybe there is another cause.
“It’s early days. But we believe that long-term COVID is not caused by one thing. That there are multiple diseases,” said Akiko Iwasaki, a professor of immunobiology at Yale University who also studies COVID long-term.
But Iwasaki and others have begun to find some tantalizing clues in the blood of some patients. Those include unusual levels of cytokines, which are chemical messengers the immune system uses to communicate, as well as proteins produced by the immune system, known as autoantibodies, that attack cells and tissues in the body instead of the virus.
“We’re finding elevated cytokines in long-term COVID patients and we’re trying to decode what those cytokines mean. We’re also seeing some clear autoantibody reactivity and trying to figure out what those antibodies are doing and whether they’re causing harm.” says Iwasaki.
Other researchers have made similar findings. dr. Steven Deeks of the University of California, San Francisco, found that patients with long-term COVID appear to have elevated levels of a cytokine called interleukin-6, suggesting they may be suffering from a state of chronic inflammation.
“The first few weeks of infection are associated with a tremendous amount of inflammation. The virus just blows up the immune system,” says Deeks. “So it’s reasonable to think that the acute COVID results in an inflammatory state in some people that can contribute to long-term COVID over time.”
Yet another clue found in a subset of patients is an unusual pattern of activity by key immune system cells, such as T cells, that may support the idea that the virus is hiding in the body.
“That’s a signature or pattern that could be consistent with a mild, but persistent infection in the patient with long-term COVID syndrome,” said Dr. Igor Koralnik of the Northwestern Feinberg School of Medicine.
While much more research is needed, the researchers hope these findings could eventually lead to ways to help patients with long-term COVID. A potential therapy for some patients could turn out to be antiviral drugs that target viruses hiding in the body. Another possibility could be: clearing the virus with a vaccine, which seems to help some long-term COVID patients. Researchers think that drugs that weaken the immune system may also help.
“We need to understand what’s going on with each patient — because the treatment option will be very different depending on what they actually have,” Iwasaki says.
Still more questions than answers
But others aren’t so sure that the evidence produced so far linking subtle changes in lab tests to physical problems in patients with long-term COVID is very convincing, including any signs that the immune system is the problem — what’s known as a car -immune disease.
“What has struck me most in a year and a half of seeing these patients and testing them extensively is that we find little to no abnormalities,” said Dr. Michael Sneller, who conducted a battery of detailed tests on hundreds of long-term COVID patients at the National Institutes of Health.
“Echocardiogram, lung function tests, X-rays, brain MRIs. You name it. Laboratory markers of organ dysfunction. We don’t see any of that,” Snelr says about the patients in his study. “And very little evidence of immune activation just looking at the kind of standard markers of inflammation. I’m running out of tests to do.”
But Sneller says his team hasn’t ruled out anything and continues to analyze immune system data. His team also conducts psychological tests on their study subjects, but not because he has doubts about their symptoms.
“It’s 100% real. These people have these symptoms. Absolutely. The question is what’s causing them,” he says. “Anxiety can cause real symptoms.”
For her part, LaDue hopes researchers will eventually figure out what’s going on with her and other patients.
“I want to feel normal and I hope to be normal again someday,” she says. “The hardest part, of course, is to look and be normal — but not feel normal.”