Study identifies potential biomarker for detecting persistent coronavirus | Health and wellness

It has been four years since the outbreak of the pandemic that rocked the world, and although the Covid virus is now under control, its hangover still lingers on millions of people. Persistent Covid, which manifests itself as a set of symptoms that last over time (more than 200 different ones have been identified), after the coronavirus infection has passed, affects every eighth person, and scientists are still trying to decipher what is behind this diverse illness. . Some studies indicate immune dysfunction; others – for the presence of a hidden reservoir of the virus; There are also those who indicate persistent inflammation; but the fundamental mechanism remains unclear. A study published this Thursday in a prestigious journal The science sheds light on this issue by identifying a potential blood biomarker for detecting persistent Covid: the researchers note that in people who become ill, there is deregulation of proteins in the component system, a network of molecules that is involved in killing pathogens. This discovery addresses the key role of the immune system in the development of persistent coronavirus and opens the door to the development of drugs aimed at eliminating this dysfunction in one of the body’s lines of defense.

By this point in January 2020, SARS-CoV-2 was already spreading silently across the globe, and the first cases of Covid began to break out everywhere. Four years later, the pandemic has claimed an estimated 778 million infections and seven million deaths, according to the World Health Organization. But there are also thousands of people in limbo, whom statistics do not take into account: these are those people who do not have active infection, but are sick; for fatigue, brain fog, muscle pain, breathing problems, or all three. “Currently, there are no diagnostic tests or therapeutic solutions for affected patients,” admit the study authors. The science. There are no treatments or tests because persistent Covid is still an unsolved mystery for scientists.

However, researchers from the University of Zurich (Switzerland) have now managed to piece together another piece of the puzzle and characterize a general pattern in persistent Covid. Scientists followed 39 healthy participants and 113 Covid patients for over a year and took blood samples from all of them at different times to identify common biomarkers among people with persistent Covid. The cohort included people infected with coronavirus but who did not have persistent covid; others who experienced symptoms for several months after infection, and people who developed post-Covid syndrome and persisted for a long time. “We took blood from patients and studied more than 6,500 different proteins. We then asked ourselves what the biggest difference was, and it lay in the proteins belonging to the complement system,” summarizes Onur Boyman, study author and head of the Department of Clinical Immunology and Allergology at the Faculty of Medicine at the University of Zurich.

Scientists found that all people with persistent Covid had dysfunction in this mechanism, which is part of the innate immune system, which is the body’s first line of defense. The complement system is a network of proteins that work in cascade, activating each other, helping to recognize and destroy harmful elements. The problem is that if this mechanism is not regulated, it can cause harm to the body. “This study showed that the complement system was active in persistent coronavirus: when patients have this disease, they also have this system active. And what’s interesting is that in the group of patients with persistent Covid there were also those who were lucky and recovered. And in these cases, the complement system also returned to normal,” explains Boyman.

The scientist explains that the complement system interacts not only with the body’s defense army, but also, for example, with the blood coagulation system. In fact, the researchers found that patients with persistent Covid had markers of impaired coagulation and tissue damage, which could explain the presence of small blood clots, Boyman suggests. And he gives an example: “The complement system also interacts with many different cells, such as blood vessel cells. If the complement system is active, these cells can be damaged. So, in a person with this damage to their endothelial cells (the ones that line the inside of the blood vessels), if they exercise, their heart pumps harder, their blood pressure increases, and this puts stress on those endothelial cells. “So these cells are under double stress, and this may explain exercise intolerance.”

The study does not specifically analyze whether deregulation of this immune system-related mechanism justifies such a varied combination of symptoms associated with persistent Covid, but Boyman emphasizes that this network of proteins is in contact throughout the body. “The complement system is made up of small proteins that can travel in the blood to all organs: the brain, lungs, intestines… and these organs can interact with all types of cells. So, in a normal situation, the complement system is fully active, not because we have a viral infection, but because this system has many different functions, such as removing dead cells. However, if you have a dysregulated complement system, it can cause damage, and the degree of damage can be very individual. For some it may be the brain, for others it may be the lungs, the intestines… It depends on the person.”

Unknowns to be solved

The study does not reveal all the unknowns associated with persistent Covid, but according to outside experts interviewed, it supports evidence about the role of the immune system in the disease. “I wouldn’t say that (complement deregulation) is a cause, but rather a factor that may explain the symptoms that people with persistent Covid experience. We don’t know if there are any other things that could predict long Covid. This condition has always been proposed with different hypotheses: due to extensive tissue damage, a viral reservoir, or due to autoimmunity and inflammation. This work shows that the immune system has a lot to do with persistent Covid,” defends Natalia Egri, an immunologist at the Hospital Clínic who was not involved in the study.

In this regard, Jeremy Nicholson, professor of medicine and director of the Australian National Phenomenology Center at Murdoch University, emphasizes that this study “helps identify some fundamental immune changes that help to understand thromboinflammatory effects (which affect the lining of blood vessels). , for example), which may lead to more generalized systemic problems (all organs have blood vessels),” but at the same time “still does not explain the diversity of symptoms of persistent covid or their differential expression between individuals.” “This article is another brick in the wall, but a complete integrative immunometabolic picture of persistent Covid has not yet emerged and requires even more comprehensive studies on a larger number of people,” the scientist adds in a statement to Scientific media center.

For his part, Marcos López-Hoyos, president of the Spanish Society of Immunology, also notes that this study demonstrates that persistent Covid is “more associated with changes in the regulation of the immune response.” The expert, who was also not involved in the study, emphasizes that it is a “robust” paper that analyzes many proteins and has a very well-controlled cohort,” but also acknowledges that the complement system “may not be the most important.” only one “factor” associated with persistent covid. Boyman admits that one of his main goals is to figure out “what keeps the complement system active” and why some patients with persistent Covid recover over time and others do not.

therapeutic target

The authors suggest that their discovery could serve as a biomarker for identifying persistent coronavirus, as well as a potential therapeutic target. “There are companies that are developing complement inhibitors. Currently, they are used for very rare immune diseases that affect, for example, the kidneys or muscles. But this study could encourage these companies, including big pharma, to pursue long-term coronavirus treatments,” Boyman agrees.

The researcher clarifies, however, that although the samples obtained, according to the patient, are somewhat similar to taking a routine blood test, the subsequent research is more complex. “We use very complex and sophisticated methods. You can’t take our method and use it in any hospital to detect the differences we find. More development will be needed, but we have shown that it can be measured, and a diagnostic company could develop a simpler test that could then be used in hospitals to more accurately diagnose persistent coronavirus,” he says.

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