Other Viruses Offer Hints Toward the Mystery of Long COVID

Aug. 18, 2022 – Researchers are chasing a spread of potential culprits within the race to seek out the causes of lengthy COVID. Some issues they agree on: There will likely be quite a lot of completely different causes, and the signs will differ wildly from case to case.

The two main theories: The persistence of the coronavirus that causes COVID-19, and an overactive immune response.

There’s proof the SARS-CoV-2 virus – or at the least items of it – can conceal out and linger within the physique, and it’s doable that is feeding an ongoing, over-the-top immune response.

Other viruses are recognized to do that. Epstein-Barr virus is seen as the reason for most instances of a number of sclerosis. Chronic fatigue syndrome, lengthy a medical thriller, has additionally been linked to viral infections.

With a fired-up immune system assembly up with a lingering virus, the causes of lengthy COVID promise to be as quite a few because the vary of signs it produces – 62, in response to a current U.Ok. examine.

Long COVID is a syndrome – a cluster of signs that may be pushed by various things in numerous individuals – says Michael VanElzakker, PhD, of the Division of Neurotherapeutics at Massachusetts General Brigham Hospital in Boston.

“So, it doesn’t have to be one cause, one symptom, one diagnosis, one treatment,” he says. “It’s a convergence of mechanisms that can drive subjective symptoms in different ways in different people.”

VanElzakker teamed up with microbiologist Amy Proal, PhD, to create the PolyBio Research Foundation in Washington state. It focuses on complicated power inflammatory ailments like myalgic encephalomyelitis/power fatigue syndrome (ME/CFS). They have been taking a look at lengthy COVID, additionally.

Writing in June within the journal Frontiers in Microbiology, they are saying lengthy COVID is usually described as uncommon or mysterious, nevertheless it shouldn’t be. It can take months or years for an individual to clear the Ebola virus, for instance. Other syndromes which may be sparked by viruses, like ME/CFS, have been related to long-term well being results and produce signs matching lengthy COVID.

VanElzakker thinks persistent virus performs a key position, however he says skeptics argue that checks that discover items of genetic materials often called RNA are simply discovering innocent remnants. Researchers are going to have to make use of a number of strategies to point out that precise leftover virus generally is a trigger, he says.

“Which is fair,” he says. “Bold claims require lots of evidence.”

While a affected person might check damaging for COVID, these bits of virus could also be lurking in different organs or methods. At the identical time, they might additionally trigger your immune system to sign a false alarm response. Data suggests the immune system could also be overresponding to residual virus.

Akiko Iwasaki, PhD, of the Department of Immunobiology on the Yale School of Medicine, and colleagues discovered proof the immune methods of lengthy COVID sufferers are reacting to one thing.

In a preprint examine that has not but been peer-reviewed, they reported they discovered proof that COVID-19 an infection had reactivated herpes viruses – Epstein-Barr virus and varicella-zoster virus, which causes chickenpox and shingles. These herpes viruses by no means depart the physique, and Iwasaki’s workforce discovered proof the immune methods of lengthy COVID sufferers is likely to be responding to those reactivated viruses.

They additionally discovered proof of exhausted immune cells often called T cells, and located that the only most evident distinction within the blood of lengthy COVID sufferers versus individuals who didn’t have lengthy COVID was the extent of the stress hormone cortisol.

Cortisol ranges “alone were the most significant predictor for long COVID classification,” they wrote.

Attacking Lung Cells

At the University of North Carolina School of Medicine in Chapel Hill, researchers have been wanting on the lungs of mice after they clear the virus to seek out out what’s driving the illness.

A workforce together with Richard Boucher, MD, director of UNC’s Marsico Lung Institute, checked out mice between 15 and 120 days after the virus had cleared and located it had contaminated cells deep within the lung. These cells have two key roles: they lubricate lungs and trade oxygen for carbon dioxide.

“So, you get a double hit early on,” he says. “You don’t have enough of these cells, so they don’t produce the lubricant that you need. Your lungs can get stiff, and it gets very difficult to breathe.”

The immune system is then triggered to assist clear up the viral an infection. In the mice, it stayed activated for as much as 4 months, their analysis discovered. “That’s probably the majority of what goes on in the lung with people post-COVID, and that will show up as shadows on a CT scan,” Boucher says.

But he and others suspect the immune response to COVID-19 can set off processes just like these seen within the early levels of pulmonary fibrosis, a progressive scarring of the lung.

“You have a lot of extra immune cells in the lung that shouldn’t have been there, and the immune cells began to put down fibrous tissue, or scar, because they couldn’t repair things,” Boucher says.

His workforce handled the mice with nintedanib, a comparatively new drug for idiopathic pulmonary fibrosis, and it seems to assist, Boucher says. The FDA accepted the drug in 2020 to deal with power fibrosing (scarring), one of many first remedies for the situation.

In earlier work, Iwasaki and colleagues, together with epidemiologist Mady Hornig, MD, of Columbia University, additionally checked out unexplained post-infection syndromes.

“Certain acute infections have long been associated with an unexplained chronic disability in a minority of patients,” they write in Nature Medicine. “These post-acute infection syndromes represent a substantial health care burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine.”

That could also be altering with analysis into lengthy COVID, Hornig says. “The pandemic is one of those turning points,” she says.

The sheer variety of sufferers and the prospect to observe them will supply solutions about these syndromes, she says. “We have at least some acknowledgment that there is the possibility of a range of disabling features that can affect a wide range of organ systems,” she says.

What stays unknown, Hornig says, is the diploma to which particular pathogens create crucial variations within the particular person’s persistent signs.

For instance, she believes that ME/CFS has a number of causes, and he or she has been investigating the issues which may be at play. While about 75% of sufferers with ME/CFS report a triggering an infection, the remaining don’t.

Another principle is that small blood clots – blood clots are an indicator of extreme COVID-19 an infection – is likely to be the foundation of among the signs of lengthy COVID.

VanElzakker from Mass General Brigham says analysis into that principle nonetheless must be repeated, however he could be shocked if the blood clots weren’t concerned.

For now, at lengthy COVID clinics nationwide, well being care professionals are treating the signs with out ready for proof of a trigger. Research into precisely what triggers the cascade of occasions affords the hope of latest remedies. Studies are underway worldwide. The Biden administration pledged assist for expanded analysis in April.