The abnormal activation of a part of the immune system, called the complement system, is at the origin of persistent covid, according to international research led by the University Hospital of Zurich. Research has identified biomarkers that can improve the diagnosis of the disease and pharmacological targets that can improve its treatment by modulating the immune system.
According to the results presented today in the journal Science, deregulation of the complement system leads the immune system to attack cells of the endothelium, which is the inner wall of blood vessels. This inflames the endothelium and increases the tendency of the blood to form thrombi. In this process, the complement system itself is reactivated, thus creating a feedback loop that makes it difficult to resolve the disease.
“In light of our data, early cardiovascular evaluation of patients with persistent Covid should be considered,” the researchers write in Science.
In the research, 6,596 proteins have been analyzed in the blood of 152 people, of which 113 had Covid in the first year of the pandemic and 39 were healthy volunteers. Among those who contracted the infection, 50% still had symptoms a month after the initial diagnosis of covid, so they were classified as cases of persistent covid. Most recovered in the following months, but 42% still had at least one symptom at six months and 19% at twelve months.
Proteomic analysis has detected 570 altered proteins in people with persistent covid. Those that have turned out to be most important are the proteins that are part of the complement system, which “may be useful to develop a diagnostic test, which is urgently needed for optimal medical care,” declares Carlo Cervia-Hasler, first author of the investigation, in an email to La Vanguardia. “There is currently no persistent Covid diagnostic test available.”
The complement system is a part of the immune system that helps eliminate pathogens and complements the action of antibodies and immune cells. It is made up of more than thirty proteins that are activated one after another by a domino effect.
In patients with persistent covid, researchers have detected excessive activation of the complement system from the acute phase of the infection. This hyperactivation is maintained in people who continue to have symptoms but not in those who recover.
In order to develop a diagnostic test based on a blood test, the most informative biomarker of persistent covid is the relationship between the C5bC6 proteins (which increase) and C7 (which decreases). The higher the level of C5bC6 and the lower the level of C7, the more the immune system attacks the endothelial cells and the more likely it is that the person will have persistent covid.
“The test could also have prognostic value,” states Cervia-Hasler. “After six months we were able to distinguish, based on markers of complement activation and thromboinflammation, between patients who were going to recover within a year and those who were not going to recover.”
After discovering that the complement system is hyperactivated in people with persistent covid, researchers have wondered why it had been activated in the first place. This has led them to track more than 80,000 antibodies against viruses, since antibodies have the ability to activate the complement system.
They have thus discovered that people with persistent covid have a high level of antibodies against viruses of the herpes family, especially against cytomegalovirus and against the Epstein-Barr virus. These extremely common viruses usually hide in the human body for their entire lives without causing symptoms. “The antibodies suggest that the viruses have been reactivated, which may have caused or maintained the activation of the complement system,” says Cervia-Hasler.
These results suggest two options to search for effective treatments against persistent covid, the researchers highlight. On the one hand, “existing therapies that act on the complement system could offer new treatment strategies for persistent covid and possibly for other post-infection syndromes,” they conclude in Science. One of these post-infection syndromes may be chronic fatigue syndrome, the cause of which has not been established but which possibly develops from an infection.
On the other hand, the researchers add, antiviral treatments against herpesviruses and against the covid virus deserve to be studied.
Before these therapies can be applied on a large scale, Cervia-Hasler warns, their effectiveness and safety will have to be studied, in which patients they are most useful, and at what point in the course of the disease they should be administered.
