Scientists are getting closer to classifying long COVID as an autoimmune disease

• Long COVID increasingly looks like an autoimmune disease.
• Research suggests that one auto-antibody in particular may lead to harmful inflammation in long COVID patients.
• These antibodies attack the body's own proteins and are a hallmark of many autoimmune diseases.

Long COVID patients may finally get an answer as to why they're still sick.

The National Institutes of Health announced Wednesday that it's kicking off a $470 million study to figure out why COVID-19 symptoms persist for so long among many patients.

Already, research has started to coalesce around a theory: The virus may set off an autoimmune reaction that causes lingering symptoms such as fatigue, shortness of breath, loss of smell, muscle aches, or brain fog.

"We can't say for sure that it's an autoimmune disease now, but it's really starting to look like it," John Arthur, a researcher at the University of Arkansas for Medical Sciences, told Insider.

In a study published this month, Arthur and his colleagues suggested that some people who get COVID-19 develop "auto-antibodies" that attack their own proteins - a hallmark of many autoimmune diseases. That process leads to inflammation that could trigger long COVID.

"Everything is sort of fitting together so far - we're just not quite totally there yet in terms of our understanding," Arthur said.

If the theory proves true, it would have implications for COVID-19 treatments. Certain blood-pressure medications, for instance, could be used to stifle the harmful cascade of inflammation. And there's already some evidence that vaccines help alleviate long COVID symptoms - perhaps because the shots help regulate the antibody response.

One particular auto-antibody could lead to inflammation in long COVID patients

One-third of coronavirus patients have at least one persistent symptom for 12 weeks or more, according to a recent study that hasn't yet been peer reviewed. Scientists have wrestled with the mystery of why that happens for more than a year.

"I see a lot of younger patients with chronic COVID symptoms and many of them have not even had any lung problems before COVID," Dr. Dixie Harris, a pulmonary physician at Intermountain Healthcare in Utah, told Insider. "They go from totally active, running marathons, to now on oxygen."

What scientists do know is that when a person gets infected, their body develops antibodies to neutralize the coronavirus. But some people's immune systems mistakenly identify those antibodies as a foreign threat themselves, so they produce auto-antibodies to fight them. That appears to be the case for many long COVID patients.

Arthur's team analyzed blood samples from 32 COVID-19 patients who donated plasma to the University of Arkansas, and another 15 who'd been hospitalized there. Around 81% of the plasma donors and 93% of the hospitalized patients had developed a particular auto-antibody that inhibited their ACE2 enzymes. These enzymes serve as ports of entry for the coronavirus to invade our cells - but they're also vital to calming the immune system down.

When not enough ACE2 is present, the immune system can produce too much inflammation.

"It's the inhibition of that ACE2 enzyme that basically is plugging up the system," Arthur said. "It's like if you've got a bunch of hair in the drain and the water starts to accumulate on top."

But more research is needed to determine for sure whether these ACE2 antibodies cause long COVID. Researchers also aren't sure yet whether severe infections produce more auto-antibodies than mild ones. A May study found that to be the case, but Arthur noted that long COVID is also common among people whose infections were initially mild.

Scientists are eyeing blood-pressure medication as a potential treatment

Arthur's study offers some evidence that medications used to treat high blood pressure could be effective as long COVID treatments.

ACE2 normally helps regulate blood pressure by a converting a chemical that raises blood pressure into one that enhances blood flow. Long COVID may prevent that conversion process, allowing that first chemical to produce harmful levels of inflammation. But high blood pressure medications can blunt this inflammatory response.

Arthur's study also suggests that vaccines could balance the levels of coronavirus antibodies and auto-antibodies among long COVID patients. A UK survey from March that hasn't been peer reviewed found that 57% of people with long COVID saw their symptoms improve after getting vaccinated.

"That's one of the things that we're going to look at in the next stage," Arthur said, "to see what vaccine status does to the abundance of these ACE2 antibodies."