Why Covid-19 hits some Sick heavier than the other, is still a mystery. A decisive role could play in the immune system. German scientists show that Chaos can cause the Virus in it.
Already in April, an international researcher noted group to Carly Ziegler from Harvard Medical School in Massachusetts, that the immune system plays during the course of a disease with Covid-19 a crucial role. The researchers described in the journal “Cell” has published a study of how the Virus throws with the help of so-called ACE2 receptors, which seizes it, the immune system completely.
Coronavirus hijacks the receptors, forcing them to replicate and multiply so infinitely
Normally, ACE2 is involved in the regulation of blood pressure. However, in the case of Covid-19 it serves as a gateway for Sars-CoV-2 into its target cells. The pathogen binds with its “barbed molecule” to the Receptor, splits the shell of the cell, and penetrates into it. Now he is hijacking the genetic material of the cell and forces it to produce countless viral copies.
This mechanism is found to be a vicious circle: In the infested tissues, Interferon is secreted, which in turn stimulates the production of ACE2. Now, more receptors are available to the Virus, so that it may intensify his attack, and also more cells affected.
The molecule prevents the blood vessels are permeable to
As if that were not insidious enough, attack of Sars-CoV-2 by ACE2 to a second Front. The Receptor not only helps to stabilize blood pressure, but also prevents the blood vessels are permeable. Both for the normal function of the lungs is essential.
- All the information from the "Cell"-Study you can read here.
Also, a German team of scientists from the Berlin Institute of Health (BIH), the Charité Berlin, as well as other researchers from Leipzig and Heidelberg, has recently shown that the immune system influences the course of Covid-19 critical. They observed that the Virus infected epithelial cells, “call the immune system to help”. However, the subsequently immigrating shoot immune cells occasionally over the target and to align with their exaggerated response partially greater damage than the Virus itself. Their findings have described the researchers in the journal “Nature Biotechnology”.
Each cell shows a different response
Roland Eils, founding Director of the Digital Health Center of BIH, and his Team relied on the so-called single-cell analyses on each individual cell, which was obtained from the respiratory tract of Covid-19 patients, examine. Because each cell responds differently to the infection, and provides individual information about the disease process, as reflected in the individual response of thousands of genes in every cell.
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In total, samples from 19 Covid-19-patients and five healthy control subjects were studied. Eight of the Covid-19-patients showed a more moderate, elf a critical course of the disease. “The samples came from the nasopharynx, of the two patients in addition to out of the bronchi. Of the five patients, we were able to repeatedly samples to win, so that we had the opportunity to follow the course of the disease in the same patient,“ says Leif-Erik Sander, the treated at the Medical clinic with focus infectiology and pneumology at the Charité, the Covid-19-patients.
More than 160,000 cells sequenced Sars-CoV-2 attaches itself to ACE2 receptors
“From the sample material we have isolated in the S3 laboratory of the Institute of Virology of the Charité under the highest safety conditions of the cells and a total of 160.528 cells sequenced,” explained Robert Lorenz Chua and Soeren Lukassen from the Digital Health centre of BIH. “In the samples we found, in addition to immune cells, especially cells from the top layer of the respiratory tract, so various epithelial cells. From these we have isolated the RNA, which contains genetic material of the Virus, but also the copies of the active genes of human cells. Based on these data and clinical information we were able to trace the infection process at the single cell level of precision.“
- All the news about the Coronavirus pandemic, you read in the News-Ticker of FOCUS Online.
Also the German scientists found that Sars-CoV-2 enters the cells it attaches itself to the ACE2 Receptor. “We have seen that the ACE2 Receptor in the epithelial cells of the Covid-19-is expressed in a patient twice to three times as much as in the epithelial cells of the non-infected control subjects,” says Christian Conrad, one of the authors of the study.
The infected cells send out a “call for help” to the immune system that attract immune cells, which help fight the infection by killing the infected epithelial cells and the Virus to neutralize it.
Unholy Alliance between Coronavirus and immune system
The immune messenger substance Interferon, which is actually a key defense strategy of the immune system against viral infections, helps in the case of Covid-19, the epithelial cells form more ACE2, and thus more vulnerable to a virus infection, explains Immunologist and head of the research group Molecular epidemiology at the BIH Irina Lehmann: “In the case of Covid-19 the immune system, thus helping the Virus to infect other cells and thus enhances the disease.” In addition, the scientists observed that, in particular, in the case of seriously ill patients, the immune cells with excessive inflammation respond.
“The single-cell analyses have shown very clearly that the Virus enters into an unholy Alliance with the immune system of the patient,” says Roland Eils. “Especially in the case of seriously ill patients, we have observed that the over-reacting is pushing the end of the immune system, the destruction of the lung tissue progressing. This could explain why these patients are more affected by the infection than patients in whom the immune system is responding appropriately.“ Why the immune system is, however, in some patients, so very out of control and not in others, remains also in this study, open.
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Results as an approach for potential therapies against Covid-19
Leif-Erik Sander adds: “These results suggest to aim our treatments at Covid-19-patients not only against the Virus itself, but also to therapies into consideration the the immune system in its place, how this can be done now with dexamethasone. You may even already at the beginning of the disease, in order to prevent an Overshooting of the immune system.“
Even before the first Covid-19 patients have been treated in the Charité, Roland Eils, and Irina Lehmann initiated this study to explore the molecular and cellular causes of Covid-19. “We suspected that the different disease, the body curves of its own immune system plays a role. And we wanted to understand in more detail“, says Irina Lehmann.
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