Aug. 18, 2022 – Researchers are chasing a variety of potential culprits within the race to seek out the causes of long COVID. Some issues they agree on: There will likely be various totally different causes, and the signs will fluctuate wildly from case to case.
The 2 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 cover out and linger within the physique, and it’s potential that is feeding an ongoing, over-the-top immune response.
Different viruses are recognized to do that. Epstein-Barr virus is seen as the reason for most instances of a number of sclerosis. Continual 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 accordance to a recent U.K. study.
Lengthy COVID is a syndrome – a cluster of signs that may be pushed by various things in numerous folks – says Michael VanElzakker, PhD, of the Division of Neurotherapeutics at Massachusetts Normal Brigham Hospital in Boston.
“So, it would not need to be one trigger, one symptom, one analysis, one remedy,” he says. “It’s a convergence of mechanisms that may drive subjective signs in numerous methods in numerous folks.”
VanElzakker teamed up with microbiologist Amy Proal, PhD, to create the PolyBio Analysis Basis in Washington state. It focuses on advanced persistent inflammatory ailments like myalgic encephalomyelitis/persistent fatigue syndrome (ME/CFS). They’ve been taking a look at lengthy COVID, additionally.
Writing in June within the journal Frontiers in Microbiology, they are saying lengthy COVID is commonly described as uncommon or mysterious, nevertheless it shouldn’t be. It will probably take months or years for an individual to clear the Ebola virus, for instance. Different 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 referred to as RNA are simply discovering innocent remnants. Researchers are going to have to make use of a number of strategies to indicate that precise leftover virus could be a trigger, he says.
“Which is honest,” he says. “Daring claims require a lot of proof.”
Whereas a affected person might check unfavorable for COVID, these bits of virus could also be lurking in different organs or methods. On the identical time, they could additionally trigger your immune system to sign a false alarm response. Information suggests the immune system could also be overresponding to residual virus.
Akiko Iwasaki, PhD, of the Division of Immunobiology on the Yale College of Medication, 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 found evidence 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 group discovered proof the immune methods of lengthy COVID sufferers could be responding to those reactivated viruses.
In addition they discovered proof of exhausted immune cells referred to as T cells, and located that the one most blatant 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 have been essentially the most vital predictor for lengthy COVID classification,” they wrote.
Attacking Lung Cells
On the College of North Carolina College of Medication 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 group 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 do not have sufficient of those cells, so they do not produce the lubricant that you just want. Your lungs can get stiff, and it will get very troublesome to breathe.”
The immune system is then triggered to assist clear up the viral infection. Within the mice, it stayed activated for as much as 4 months, their analysis discovered. “That is most likely nearly all of what goes on within the lung with folks post-COVID, and that may present up as shadows on a CT scan,” Boucher says.
However 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 could have quite a lot of further immune cells within the lung that should not have been there, and the immune cells started to place down fibrous tissue, or scar, as a result of they could not restore issues,” Boucher says.
His group handled the mice with nintedanib, a comparatively new drug for idiopathic pulmonary fibrosis, and it seems to assist, Boucher says. The FDA authorized the drug in 2020 to deal with persistent fibrosing (scarring), one of many first remedies for the situation.
In earlier work, Iwasaki and colleagues, together with epidemiologist Mady Hornig, MD, of Columbia College, additionally checked out unexplained post-infection syndromes.
“Sure acute infections have lengthy been related to an unexplained persistent incapacity in a minority of sufferers,” they write in Nature Medicine. “These post-acute an infection syndromes characterize a considerable well being care burden, however there’s a lack of know-how of the underlying mechanisms, representing a major blind spot within the area of medication.”
That could be altering with analysis into lengthy COVID, Hornig says. “The pandemic is a kind of turning factors,” she says.
The sheer variety of sufferers and the possibility to watch them will provide solutions about these syndromes, she says. “Now we have at the least some acknowledgment that there’s the potential of a variety of disabling options that may have an effect on a variety of organ methods,” 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. Whereas about 75% of sufferers with ME/CFS report a triggering an infection, the remainder don’t.
One other idea is that small blood clots – blood clots are a trademark of extreme COVID-19 an infection – could be the basis of a number of the signs of lengthy COVID.
VanElzakker from Mass Normal Brigham says analysis into that idea nonetheless must be repeated, however he can 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. Analysis into precisely what triggers the cascade of occasions affords the hope of latest remedies. Research are underway worldwide. The Biden administration pledged support for expanded analysis in April.
