Understanding Long COVID: Study Finds Biological Difference In People With Prolonged Infection

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University of New South Wales (UNSW) researchers have discovered that people who develop long COVID are biologically different, with their immune systems uniquely responding to the virus.

UNSW’s ADAPT study was intended to observe the mental health and neurological, respiratory and cardiac functions of patients that had contracted COVID-19 to determine how the body was affected by the virus. However, the study also found that those with symptomatic long COVID still had activated immune cells.

“The long COVID patients were showing abnormal immune signals at about eight months post-infection,” Prof. Gail Matthews, co-author of the paper, said in a UNSW news release. “We wouldn’t expect to see that in somebody who had recovered from a viral illness.”

“So this was an important finding because it showed unequivocally that biologically, people who had long COVID were different from those who'd had COVID and fully recovered,” she explained.

“This is only one piece of a big puzzle,“ Matthews said. ”We haven’t found the answer to long COVID, but what we have found is a signal.”

Long COVID is a term coined on Twitter in May of 2020 by Dr. Elisa Perego, from Lombard, Italy, who was taking a long time to recover from COVID, having on and off symptoms. Dr Perego used the term to describe her symptoms of a cyclic and progressive COVID-19 infection that had multiple phases.

The condition is now recognized by the World Health Organization (WHO), which refers to it as “post-COVID-19” and defines it as a condition that usually arises three months after the onset of a COVID infection and lasts at least two months. The WHO estimates that around 10-20 percent of people who contract the virus develop post-COVID-19.

In the largest study of its kind, published recently in the journal BMJ, researchers estimated that 32% of older adults in the U.S. who survived covid infections had symptoms of long COVID up to four months after infection—more than double the rate an earlier study found in adults ages 18 to 64. (Other studies suggest symptoms can last much longer, for a year or more.) ShutterStock

Matthews explained that the immune system, when the body has caught any viral illness, produces several signals called cytokines, and they are markers in the blood that inform the immune system that the body has a virus.

“And that’s often what’s responsible for some of the symptoms we get when we’re sick such as fever or feeling unwell.”

But she noted that after the infection is resolved, the immune system usually settles down to its “resting state.”

“And that’s what we saw in the people who recovered from COVID. But in the people who had long COVID, the signals from the immune system suggested it was still trying to activate,” she explained.

“It was still trying to get rid of something that shouldn’t be there eight months after having had the initial infection.”

She said that while there had scepticism about the existence of long COVID initially, she believes that her research now proves it is a real syndrome.

Inflammation around the lining of the heart (pericarditis) and the lining of the lungs (pleuritis) may also occur in long COVID.wavebreakmedia/Shutterstock

For Matthews, the ADAPT study is crucial because it was established around April 2020, just after the pandemic began.

“We started following people who had COVID-19 infections at the time, but we didn’t know there was anything like long COVID,” she added.

Through following their patient’s progress, the researchers soon determined that 30 percent of people managed in the community had not yet recovered four months after their initial COVID-19 infection.

“And in fact, that group had still not recovered at eight months post-infection. So, that was the first important recognition of long COVID occurring in Australia,” she said.

“We were seeing similar reports coming out of the US and the UK, but ADAPT was the first Australian study to really document very clearly that this was an issue.”

The most common symptoms of long COVID are persistent fatigue, brain fog and concentration difficulties, respiratory symptoms such as an incessant cough, and shortness of breath. Some people suffering from prolonged infection also experienced a high heart rate that did not settle.

“In fact, up to 100 different symptoms have been described as part of the long COVID spectrum,” she said. “Some of our patients who’ve been very unwell when they’ve been in hospital with COVID-19 have certainly taken a long time to recover.”

“It could be because they’ve got scarring in their lungs, or just because they’ve been very sick in hospital. And that’s not too surprising.”

However, Matthews said that there are many people who have developed long COVID, despite never being hospitalized.

“They may have had some symptoms at home, but they were managed in the community. It was not severe enough to go to hospital, but they still have symptoms some months afterwards,” she explained.

The CDC says long COVID is a wide range of new, returning or ongoing physical and mental health problems people can experience four or more weeks after first getting infected with SARS-CoV-2, the virus that causes COVID-19. Shutterstock

Mathews believes, though, that despite the extended healing time for many long COVID patients, there will be a recovery.

“The data suggests that even if you develop long COVID, most people will improve over time.”

“We’re about to do a two-year follow up of people who were infected in March 2020, and what we hope to see is that most people have recovered without significant long term impacts to their health.”

“I think we’re still learning a lot about long COVID,“ she said. ”But we’ve come a long way from where we were in mid-2020, which is when long COVID first started to be talked about, especially among patients themselves to start off with.”

The results of the ADAPT study were published in the scientific journal Nature.