Scientists from the UK's University of Cambridge have found that persistently high levels of the immune molecule interferon-gamma are associated with a subgroup of patients with long-term Covid.
Scientists from Great Britain believe they have discovered valuable new evidence that could help in the diagnosis and treatment of long-term covid sufferers.
Around the world, at least 65 million people are still living with long-term covid - that's about one in ten people who had covid-19, according to the World Health Organization (WHO).
WHO describes long-term covid as the continuation or appearance of new symptoms three months after the original covid infection, and that these symptoms last for at least two months without any other explanation.
Scientists are investigating many different aspects of long-term Covid, but one of the most important things they are looking for is a measurable biomarker - a biological molecule in blood, other body fluids or tissues that can be reliably taken as a sign of a condition or disease.
The discovery of biomarkers for long-term covid would represent a significant advance in the diagnosis and follow-up of the treatment of patients and to dispel the theory that long-term covid is a psychological disease.
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Identification of long-term covid
Dr. Njari Sithol, an infectious disease clinical scientist at the University of Cambridge, opened one of the first long-term covid clinics back in May 2020.
A clinic at Addenbrooke's Hospital in Cambridge tried to discover potential biomarkers in people suffering from long-term covid - or some subgroup of them.
In operation published in the journal Science Advances (Science Advances), the clinic announced this week that there was an important development in their studies.
Collaborating with colleagues Dr. Mark Willis and Dr. Benjamin Krishna, Dr. Sithole divided the studies into subgroups because long-term covid is believed to be a disease with multiple syndromes.
This means that it is not a single disease process, but rather a number of conditions grouped together under the same umbrella name, making it unlikely that a single biomarker can be found to cover all patients with long-term covid.
In one subset of patients, scientists discovered a protein known as interferon-gamma (IFN-γ), which produces a type of white blood cell to help fight the bacteria and protect you from disease.
This protein initially produces immune reactions when the patient is first infected with covid.
Almost all patients infected with covid-19 produce interferon-gamma, as well as other immune molecules or cytokines.
Researchers have found that in patients who recover from covid, their interferon-gamma returns to pre-infection levels within a few weeks.
However, in patients with long-term covid, interferon-gamma levels remain above normal for more than 12 weeks, and in some patients even two years later.
On average, patients with long-term covid had interferon-gamma levels at least 10 times higher than unexposed controls.
"In patients with long-term covid, there is a dysregulation of the immune system," explains Dr. Sithol.
"The immune system does not 'reset' to normal levels or normal functional status after covid and remains in a heightened state of alert - as if it is still at risk."
These increased levels of protein can also cause inflammation and because they are released into the bloodstream it can spread to various organs.
One hypothesis for elevated levels of interferon-gamma, Dr. Sithol suggests, is that there could be viral fragments or viral proteins in the body of patients with long-term covid.
"Some research groups are looking at biopsies of the colon and other areas of the body to see if they can detect the virus in those locations," he says.
"There could be a very small level of virus that is still replicating, or these proteins are still circulating and tricking the immune system into constantly thinking that a pathogen is present in the body."
Another hypothesis is that the results are caused by autoantibodies.
Normally, human immune systems make antibodies to fight disease.
But sometimes the body turns against itself, creating autoantibodies that attack healthy cells.
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Is an elevated level of interferon-gamma a biomarker for long-term covid?
There is evidence that persistent release of interferon-gamma occurs after other diseases such as infectious mononucleosis, and in other diseases interferon-gamma is known to cause symptoms including fatigue, joint and muscle pain, and fever.
Dr. Sithol and his colleagues were able to analyze various cytokines (immune molecules) in the blood of patients before vaccination began in the UK, and compared them with their blood after vaccination.
Some patients with increased levels of interferon-gamma returned to normal baseline levels after vaccination (however, not all).
In addition, a significant number of patients with long-term covid noticed that their symptoms weakened after vaccination.
Further research on larger groups is needed, but this study shows a link between interferon-gamma reduction and improvement in symptoms, and therefore gives hope that interferon-gamma could be used to diagnose and monitor some patients with long-term covid.
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