Four years are regarding to pass since the outbreak of a pandemic that shook the world and although the covid virus is now controlled, its hangover still weighs on millions of people. Persistent covid, which manifests itself with an amalgam of lasting symptoms over time – there are more than 200 different ones identified – following passing the coronavirus infection, affects one in eight people, and scientists are still trying to decipher what is behind this heterogeneous ailment. Some studies point to immune dysfunction; others to the presence of a hidden viral reservoir; There are also those who point to persistent inflammation; but the fundamental mechanism remains unclear. A study published this Thursday in the prestigious magazine Science sheds light on this point by identifying a potential blood biomarker to detect persistent covid: researchers point out that affected people present a deregulation in the proteins of the component system, a network of molecules that participates in the destruction of pathogens. The finding affects the key role of the immune system in the development of persistent covid, and opens the door to designing drugs aimed at reversing this dysfunction in one of the body’s lines of defense.
At this point in January 2020, SARS-CoV-2 was already spreading silently around the globe and the first cases of covid were beginning to break out everywhere. Four years later, the pandemic has left, according to the World Health Organization, around 778 million infected and seven million dead. But also thousands of people in a limbo that the statistics do not count: they are those individuals without active infection, but sick; with fatigue, brain fog, muscle pain, breathing problems or all at once. “Currently, there are no diagnostic tests or therapeutic solutions for affected patients,” admit the authors of the study. Science. There are no treatments or tests because persistent covid is still, for scientists, a half-finished puzzle.
However, researchers from the University of Zurich (Switzerland) have now managed to put another piece of the puzzle together and characterize a common pattern in persistent covid. Scientists followed 39 healthy participants and 113 Covid patients for more than a year and took blood samples from all of them at different times to identify common biomarkers of people with persistent Covid. In the cohort there were people infected with coronavirus, but who did not have persistent covid; others who suffered symptoms for a few months following infection and individuals who developed this post-covid syndrome and maintained it over time. “We took blood from patients and looked at more than 6,500 different proteins. Then we asked ourselves what the biggest difference is and that was in the proteins that belong to the complement system,” summarizes Onur Boyman, author of the study and head of Clinical Immunology and Allergology at the Faculty of Medicine of the University of Zurich.
The scientists detected that people with persistent covid all had a dysfunction in this mechanism that is part of innate immunity, which is the body’s first line of defense. The complement system is a network of proteins that work in a cascade, activating each other to help recognize and destroy harmful elements. The problem is that if this mechanism is deregulated, it can be harmful to the body. “This study showed that the complement system was active in persistent covid: when patients have this condition, they also have this system active. And what’s interesting is that in the group of patients with persistent Covid, there were some who were lucky and recovered. And in those cases, the complement system also returned to normal,” explains Boyman.
The scientist explains that the complement system not only communicates with the body’s defense army, but also with the blood coagulation system, for example. In fact, researchers found that patients with persistent Covid had markers of impaired coagulation and tissue injury, which might explain the presence of small blood clots, Boyman suggests. And he gives an example: “The complement system also communicates with many different cells, for example, the cells found within blood vessels. If the complement system is active, those cells can be damaged. So, in an individual who has such endothelial cell damage [las que recubren el interior de los vasos sanguíneos]If you exercise, your heart pumps more, blood pressure increases and that puts stress on those endothelial cells. So, these cells have double stress and this may explain exercise intolerance.”
The study does not specifically analyze whether the deregulation of this mechanism associated with the immune system justifies this varied mix of symptoms linked to persistent covid, but Boyman emphasizes that this network of proteins is in contact with the entire organism. “The complement system consists of small proteins that can go with the blood to all the organs: the brain, the lungs, the intestine… and these organs can interact with all types of cells. So in a normal situation, the complement system is fully active, but 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 extent of the damage can be very individual. In some people it can be the brain, in others the lungs, the intestine… It depends on the person.”
Unknowns to be resolved
The research does not resolve all the unknowns surrounding persistent covid, but, according to the external experts consulted, it does support the evidence on the role of the immune system in the condition. “I wouldn’t say that [la desregulación del sistema del complemento] It is not the cause, but a factor that might explain the symptoms that people with persistent covid have. We don’t know if there are other things that might predict long Covid. This condition has always been proposed with different hypotheses: due to a lot of 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 has not participated in the research.
Along these lines, Jeremy Nicholson, professor of Medicine and director of the Australian National Phenome Center at Murdoch University, highlights that this study “helps identify some fundamental immune alterations that help to understand the thromboinflammatory effects (which affect the lining of blood vessels). , for example) that can give rise to more generalized systemic problems (all organs have blood vessels)”, but at the same time, “it still does not explain the diversity of the symptoms of persistent covid or their differential expression between individuals.” “This article is another brick in the wall, but the complete integrative immunometabolic picture of persistent covid has yet to emerge and requires even more exhaustive studies in a larger number of people,” adds the scientist in statements to Science Media Centre.
For his part, Marcos López-Hoyos, president of the Spanish Society of Immunology, also points out that this study demonstrates that persistent covid “is more linked to an alteration in the regulation of the immune response.” The expert, who has not participated in the research either, highlights that it is a “robust” article, where many proteins are analyzed and there is a very well-controlled cohort,” but also admits that the complement system “may not be the only one.” factor” associated with persistent covid. Boyman acknowledges that one of his great concerns is to find out “what keeps the complement system active” and why some patients with persistent covid recover over time and others do not.
therapeutic target
What the authors do suggest is that their finding can serve as a biomarker to detect persistent covid and also as a potential therapeutic target. “There are companies that develop complement inhibitors. Currently, they are used for very rare immune diseases that affect the kidneys or muscles, for example. But this study might motivate those companies, which include big pharma, to address the treatment of long covid,” agrees Boyman.
The researcher clarifies, however, that although the samples obtained are, in the patient’s view, something similar to taking an ordinary blood test, the subsequent study is more complex. “We use very complicated and sophisticated methods. You cannot take our method and use it in any hospital to detect the differences that we detected. More development would be needed, but we showed that this can be measured and a company that is dedicated to diagnosis might develop a simpler test that might then be used in hospitals to make a better diagnosis of persistent covid,” he says.
