Long Covid: a step towards a blood test to facilitate diagnosis

While most of the Covid-19 pandemic is in the past, many patients around the world are still dealing with the virus in its persistent form. It is estimated that between 4% and 10% of people infected with Sars-CoV-2 will suffer from long Covid, with symptoms lasting several weeks or even several months after initial contamination. In France, 2 million patients are affected. But from chronic shortness of breath to memory, muscular or digestive problems, the symptoms remain very diverse. Which makes his diagnosis particularly tricky.

In the absence of specific medical criteria, doctors often proceed by elimination, excluding all other possible causes of the symptoms experienced. A laborious process, which leaves many patients in the dark for some time. However, advances in research have taught us that these patients present with immune and hormonal dysfunction. Hence the idea of ​​looking for “markers” of long Covid directly in the blood of patients. A team of Swiss and American researchers managed to identify new specific molecules that could help with diagnosis.

Also read: Long Covid, a new chronic disease

In this study published in Science, scientists screened blood samples from 113 patients infected with Sars-CoV-2 and 39 healthy controls. All participants were followed for one year. After 6 months, 40 of the infected patients had persistent symptoms and were therefore diagnosed with long Covid. Using a proteomic approach which consisted of comparing the levels of 6,596 proteins in the blood serum of all participants, the authors sought to identify potential blood markers in these patients with long Covid.

It emerged that these patients presented specific changes in their serum protein levels, indicating increased activation of the complement system, a component of the immune system involved in the fight against pathogens. “The complement system has a dual role, on the one hand in regulating the immune system, and on the other hand in interfering with coagulation factors and the blood vessel. Usually, this mechanism is activated during the acute phase of the disease but returns to normal once the infection has passed,” explains Professor David Smadja, hematologist at the Georges-Pompidou European Hospital (AP-HP and university Paris-Cité) and researcher in the therapeutic innovations in hemostasis unit at Inserm.

However, in long Covid, the complement system “goes into overdrive” chronically, promoting tissue damage. Such hyperactivity was specifically correlated with a variation in some of the proteins that make up the complement system (increase in C5b-C6, decrease in C7). The researchers therefore suggest that these proteins could serve as markers for long Covid.

Also read Can the vaccine relieve the symptoms of long Covid?

But that's not all. This abnormality in complement system activity was also coupled with signs of persistent thromboinflammation, a pathophysiological mechanism that results in the formation of blood clots (thrombosis) combined with a chronic inflammatory response.

In the patients in the study, this thrombo-inflammatory signature was characterized by an increase in the level of the protein thrombospondin-1 and von Willebrand factor, two players promoting the coagulation of blood cells (platelets) and damage to blood cells. blood vessels. “These results confirm that the complement system and the blood vessel are two parameters which appear to be dysfunctional in long Covid, and which would a priori be detectable by a simple blood test,” underlines Professor Smadja.

Also read: Post-infectious syndrome, a long-known phenomenon

Be careful, however, because researchers doubt that we will one day be able to identify a universal biomarker for long Covid. “The different symptoms show very clearly that there are very different clinical forms,” insists Professor Jérôme Estaquier, Inserm research director in the environmental toxicity, therapeutic targets, cell signaling and biomarkers unit at Inserm. “In reality, we should rather talk about “long” Covids, adds Professor Smadja. This is important because it suggests that there are several biological markers, probably specific to each clinical form. »

Other work has already reported a certain number of blood biomarkers for long Covid, in particular the presence of persistent antibodies to the virus, vascular proliferation or even unusual activity of a subpopulation of T lymphocytes. (CD8). It is therefore very difficult to know whether the newly identified biomarkers can be used routinely. “For this, the results will have to be replicated and differentiated according to the main categories of respiratory, neurological, digestive, and cardiac symptoms of long Covid,” indicates Professor Estaquier.

Another limitation is that the identification of biomarkers for long Covid could depend on other parameters, such as sex or age. “We know that long Covid tends to appear more often in women and that age can influence the differential activation of the complement system. Future studies will therefore have to be very attentive to these parameters,” concludes Jérôme Estaquier.