Deciphering the molecular signature of long-Covid

For this reason, Gyöngyösi’s team is currently looking for molecular biological markers, such as certain microRNAs, so-called cell-free DNA in body fluids or protein signatures. “We analyzed the proteins in the blood of 100 patients, for instance, and found that some were boosted and others declined. These proteins can act as biomarkers pointing to an immune system that is out of kilter,” says the cardiologist. The results are currently being verified in a larger patient cohort, but the initial findings have already been honored with an award from the American Society of Cardiology.

Diagnostic approaches are now to be interlinked

“Long-Covid is a multi-organ disease, which is why it is difficult to find a single biomarker that is specific for all organs or all symptoms. What we need instead is network medicine, i.e. we need to look at the entire system of many different, small alterations,” says Gyöngyösi. This is the approach she now wants to take so as to raise the research project to a new level. To this end, the clinician is collaborating with experts from the fields of bioinformatics and molecular biology with a view to combining diagnostic data. This includes techniques such as magnetic resonance imaging, traditional clinical examinations and new molecular biology approaches.

“It is essential that we combine these levels – imaging, clinical data and molecular biology. That may help us find a set of parameters that enables us to determine whether a person has long-Covid and to estimate the course of the disease. This is important from a diagnostic point of view, but also because it can inform research for a therapy,” Gyöngyösi notes.

No specific therapy to date

Over 600 patients have already been registered in the long-Covid study outpatient clinic. Their data provide important insights, with one publication from the project showing that a Covid-19 vaccination reduces the severity of multi-organ symptoms in long-Covid. The reactivation of other viruses dormant in the body is also likely to play a role – a study from Gyöngyösi's team showed that vaccination also helps in this respect.

Apart from this preventive effect, the therapy has so far remained purely symptomatic and correspondingly complex: “There are over 200 documented symptoms for long-Covid. One patient may have a problem with blood clotting, another has residual abnormalities in the lungs, a third patient has muscle pain and a fourth has a psychosomatic illness,” Gyöngyösi notes, reporting on her experiences from the outpatient clinic. The most common symptoms affect the nervous system, followed by the cardiovascular system and the lungs. Around 60 to 70 percent of those affected are women.

Exercise intolerance, for example in the form of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is typical of long-Covid. Circulatory problems are also common. “In general, we speak of long-Covid when patients still experience symptoms three months after an infection or new complaints have developed,” explains the doctor.

Knowledge gained since the pandemic

When Gyöngyösi started the research project in mid-2022, over 100 million people worldwide were infected with the Covid-19 virus. “Back then, there were only a handful of publications on cardiological treatment in the databases. Three years later, there are over 20,000 specialist articles and we know much better how we can alleviate patients' symptoms,” says Gyöngyösi. In addition, more and more research results indicate that the symptoms do not occur only as a result of a Covid-19 infection, but generally after viral infections, for example influenza viruses. “We call this 'post-viral syndrome'. With long-Covid, the post-viral symptoms last longer – years, in some cases – and are more severe than with influenza,” explains Gyöngyösi.

In spite of all this, the doctor is optimistic: “I see good chances of recovery, especially in patients where we can't pin down any objective findings. In many cases, we see that they suddenly feel better again after two or three years. We have to give those affected this hope.”