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Scientists have linked high levels of an antiviral protein to long Covid, boosting efforts to detect the debilitating condition and develop therapies to treat millions of sufferers worldwide.
Patients showed persistently elevated readings of interferon-gamma (IFN-γ), which is associated with fatigue, aching muscles and depression, according to research published in the journal Science Advances on Wednesday.
The findings suggest the protein could be used to detect long Covid and investigated as a possible therapy for sufferers who report extreme fatigue.
“The presence of interferon-γ could be used to diagnose long Covid in some patients,” said Benjamin Krishna, co-author of the paper and a Cambridge university researcher. “In addition, it could be targeted to then treat their symptoms.”
Researchers have highlighted the need to find “biomarkers” for long Covid — biochemical changes that are a signature of the condition. A study published last month pointed to changes in the “complement system”, a group of proteins that help the body fight infections.
Long Covid — defined as symptoms or conditions that last more than 12 weeks after initial infection with Covid-19 — has become a growing burden for public health systems since the emergence of the coronavirus pandemic four years ago. Sufferers report an array of symptoms including acute fatigue, shortness of breath and cognitive impairment or “brain fog”.
The study followed patients from a long Covid clinic at Addenbrooke’s Hospital in Cambridge, England, including cases from 2020. It tested the blood of 55 people who were experiencing symptoms — predominantly fatigue — at least five months after contracting Covid-19.
The researchers found that Covid-19 infection triggered IFN-γ production by white blood cells — and this persisted in the long Covid patient cohort. More than 60 per cent of the sample group reported a reduction in at least some of their symptoms during the study, with their IFN-γ levels also falling.
IFN-γ plays an important role in regulating the body’s response to pathogens. It is used clinically to damp infections in people whose immune systems have been compromised by chronic granulomatous disease, a genetic disorder that makes people susceptible to dangerous bacterial and fungal infections.
The discovery of a biomarker to confirm the prevalence of long Covid would offer hope to patients who worry that their condition may be dismissed by doctors, scientists say.
“When the clinic started, a lot of people didn’t even believe long Covid was real,” said Nyarie Sithole, who set up the Addenbrooke’s long Covid facility.
Long Covid’s causes are yet to be well established but is estimated to affect 5 per cent of people who contract the virus. It is associated with problems including abnormalities in vital organs, microclots, reduced serotonin and persistent levels of the Covid-19 virus.
The Addenbrooke’s research is an “interesting study proposing a new mechanism for long Covid”, said Aran Singanayagam, a respiratory physician at Imperial College London. Evidence that IFN-γ levels fell as symptoms eased was a particular “strength” of the paper, said Singanayagam, who was not involved in the study.
Further work would need to look at patients with a wider range of symptoms than fatigue since it seemed unlikely that a single mechanism such as raised IFN-γ “would be responsible for driving all forms of long Covid”, said Singanayagam.
He also noted that the study did not confirm whether the protein was a “causal driver” of long Covid — and thus a good target for potential treatments.
