Immune system failure found to cause persistent Covid

According to an international study conducted by the University Hospital of Zurich, abnormal activation of a part of the immune system called the complement system is the cause of persistent coronavirus. Research has identified biomarkers that can improve 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 The scienceDeregulation of the complement system causes the immune system to attack endothelial cells, which are the inner wall of blood vessels. This inflames the endothelium and increases the blood’s tendency to form blood clots. In this process, the complement system itself is reactivated, thereby creating a feedback loop that makes it difficult to treat the disease.

Immune proteins attack the blood vessels, which increases the immune response and makes healing more difficult.

“In light of our data, early cardiovascular evaluation of patients with persistent Covid should be considered,” the researchers wrote in The science .

The study analyzed 6,596 proteins in the blood of 152 people, of whom 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 their initial covid diagnosis and were therefore classified as persistent covid cases. Most recovered in the following months, but 42% still had at least one symptom after six months, and 19% after twelve months.

Proteomic analysis identified 570 altered proteins in people with persistent Covid. The most important were proteins that are part of the complement system, which “may be useful for the development of a diagnostic test that is essential for optimal medical care,” says Carlo Cervia-Hasler, first author of the study, in an email to Vanguard . “There is currently no consistent diagnostic test for Covid.”

Persistent Covid increases the risk of blood clots; Researchers advocate for patients’ cardiovascular control

The complement system is part of the immune system that helps eliminate pathogens and complements the action of antibodies and immune cells. It consists of more than thirty proteins that are activated one after another in a domino pattern.

In patients with persistent Covid, researchers found excessive activation of the complement system during the acute phase of infection. This hyperactivation persists in people who continue to have symptoms, but not in those who recover.

For the development of a diagnostic test based on a blood test, the most informative biomarker of persistent covid is the relationship between the C5bC6 (which increases) and C7 (which decreases) proteins. The higher the C5bC6 level and the lower the C7 level, the more the immune system attacks endothelial cells and the more likely a person is to have persistent Covid.

“A diagnostic test is urgently needed,” says the study’s first author.

The test may also have predictive value, says Cervia-Hasler. “After six months, we were able to distinguish, based on markers of complement activation and thromboinflammation, between patients who were expected to recover within a year and those who were not expected to recover.”

After discovering that the complement system was hyperactivated in people with persistent Covid, researchers wondered why it was activated in the first place. This allowed them to track more than 80,000 antibodies against viruses, since antibodies have the ability to activate the complement system.

The results show how persistent Covid can be treated by modulating the immune system.

Thus, they found that people with persistent Covid have high levels of antibodies against viruses of the herpes family, especially against cytomegalovirus and against Epstein-Barr virus. These extremely common viruses usually hide in a person’s body throughout their entire life without causing symptoms. “The antibodies suggest that the viruses were reactivated, which could cause or maintain activation of the complement system,” says Cervia-Hasler.

These results suggest two options for finding effective treatments for persistent coronavirus, the researchers emphasize. On the one hand, “existing therapies targeting the complement system may offer new strategies for treating persistent coronavirus and possibly other post-infectious syndromes,” they conclude. The science . One of these post-infectious syndromes may be chronic fatigue syndrome, the cause of which has not been established, but may develop against the background of infection.

On the other hand, the researchers add, antiviral treatments for herpes viruses and the covid virus are worth exploring.

Before these treatments can be used on a large scale, Cervia-Hasler warns, their effectiveness and safety must be studied, to determine which patients benefit most from them and at what point in the disease course they are appropriate to use.

Unknown

How many victims are there?

About 5% of people infected with the Covid virus go on to develop long Covid, researchers from the University of Zurich report using data from 2020 and 2021. But because long Covid is associated with the immune system’s response to infection, and this response was different in the population without covid immunity in the early months of the pandemic than in the current population, data from 2020 and 2021 cannot be extrapolated to the present. “Although the risk of persistent Covid is now lower than at the start of the pandemic, it is not zero and millions of people are still affected; Vaccines are the most effective way to reduce the incidence of disease,” says Roger Paredes, head of the infectious diseases service at the Can Ruti Hospital in Badalona. It is unknown what exactly this risk is and how many people are currently affected.

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Joseph Corbella