Blood protein changes offer clue to solving long Covid riddle

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Changes in blood protein have been found in people suffering with long Covid, according to research that will boost efforts to diagnose and devise treatments for a debilitating condition affecting tens of millions of people worldwide.

The research adds to the growing mix of factors that appear to contribute to long Covid months or years after initial infection. An estimated 5 per cent of people who contracted the virus are thought to have the condition, creating a growing burden on public health systems that have struggled to recover from the demands of Covid-19’s pandemic phase.

The central finding of the research, published in Science on Thursday, is the importance of the “complement system” — a group of proteins that collectively helps the body fight off infections, but whose localised activation was seen as a potential cause of increased inflammation.

“This was a piece of the puzzle that has been missing that explains so many different manifestations of long Covid,” said Onur Boyman, a University of Zurich professor and leader of the research. “This provides an opportunity to better diagnose and potentially even treat the condition.”

Boyman’s team measured the levels of more than 6,500 blood proteins in 113 people who had either fully recovered from Covid or developed the long form of the respiratory disease. The 40 long Covid sufferers exhibited effects including abnormal activation of the complement system, the researchers found.

The latest study is important because it “nails the role” in long Covid of the complement system’s inflammation of blood vessel walls, according to Eric Topol, director of the Scripps Research Translational Institute in California. 

It raises the prospect that blood protein changes might serve as one of the biological indicators or biomarkers that will help medical practitioners identify patients’ susceptibility to long Covid.

“[This] new data . . . could help develop a diagnostic biomarker, which could also be used to follow patients with long Covid to see if there is reduction of inflammation,” said Topol, who was not involved in the study.

Long Covid has emerged as a lingering destructive effect of the pandemic; symptoms include acute fatigue, shortness of breath and cognitive impairment — often referred to as “brain fog”. People lost more “healthy life years” to the syndrome in the first two years after infection than they would to cancer or heart disease, according to a study published in August.

Previous research has found how long Covid — defined as symptoms or conditions that last 12 weeks or more after diagnosis — is associated with problems including abnormalities in vital organs, microclots, reduced serotonin and persistent levels of the Covid-19 virus.

The complement system’s significance is another sign of how the syndrome shares traits with autoimmune diseases such as multiple sclerosis. In these complex conditions, many of which have yet to be comprehensively explained, the defensive response to pathogens ends up damaging the body itself.

Long Covid’s causes appeared to be similarly “heterogeneous” and bigger studies would be needed to tease out how they interact with each other, said Aran Singanayagam, a respiratory physician at Imperial College London. 

“It’s a really frustrating condition to try and treat,” said Singanayagam, who welcomed the latest research. “It’s one of the most difficult — if not the most difficult — thing that we see currently.”

Claire Steves, professor of ageing and health at King’s College London, said larger studies were needed into the significance of blood proteins for prolonging Covid symptoms. “This study includes a very small number of individuals living with long Covid.”