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An infection with a pathogen usually triggers a well-coordinated choreography of the defense: natural killer cells become active, T helper cells support B cells in the formation of antibodies, T killer cells begin to destroy infected cells, and in anticipation of blood and oxygen loss, more platelets are formed for blood clotting.
In the case of a serious illness from Covid-19, the complex choreography seems to derail: “Usually an infection or a virus defense is a self-limiting course: We know that certain messenger substances are released between the cells and certain cell types occur at certain times. For some However, something happens to patients, especially those at risk, which can be severe or even fatal. All of a sudden, the patients turn the wrong way, “says Philip Rosenstiel. The molecular biologist at the University of Kiel has worked with various research teams to investigate when this happens and which processes indicate early on such a “turning” towards a potentially fatal course.
Not like the flu
Worldwide, over 115 million people were infected with the new coronavirus within one year. 2.66 million people have died from or with the virus so far, 519,519 in the United States alone. The reasons why some people die of Covid-19 and others do not, some have to be ventilated and others do not, are still largely unanswered questions.
Covid-19 seems to be particularly easy to get people to “turn around”: The risk of pulmonary embolism, cardiac arrhythmias, kidney failure and multiple organ failure is higher in Covid-19 patients compared to influenza patients, as is mortality. People with obesity, diabetes or cardiovascular disease are particularly at risk, as are men. “Covid-19 is not comparable to other serious lung diseases. We have never had so many patients with severe lung failure in our intensive care unit for weeks, that is no comparison to the flu,” reports Arshang Valipour, head of the department for internal medicine and pulmonology at the Floridsdorf Clinic in Vienna.
The lung specialist observes that increasingly younger patients are in his intensive care unit, people in their thirties, forties and fifties. He suspects that this could possibly have something to do with the British variant of the coronavirus. What all intensive care patients in his department have in common is that they belong to at least one of the top 3 risk groups: They suffer from obesity, have diabetes or some form of cardiovascular disease. “Every patient has at least one risk factor, many have several,” says Valipour.
In order to understand what happens in patients when they go through an infection, the cellular processes of the immune defense come into the focus of the researchers. Together with others, Rosenstiel succeeded in identifying markers for a severe course by observing the ebb and flow of cells of certain types and of certain messenger substances during an illness.
Over time, the scientists observed that the immune reaction is sometimes excessive, up to a tipping point at which the virus defense turns against its own body.
Unfinished platelets
So-called megakaryocytes seem to play a special role. These are immature cells that are formed in the bone marrow and that are actually supposed to become mature blood platelets. Platelets help blood to clot. With Covid-19, the unfinished platelets are flushed out of the bone marrow in large quantities at once. This also happens with other serious illnesses, such as blood poisoning. With Covid-19, the megakaryocytes appear early, although there is still no acute emergency. Your appearance, Rosenstiel noted, is a sure sign of a very difficult course. “The megakaryocytes outside the bone marrow indicate that the body interprets the Sars-CoV-2 infection as an absolute emergency at an early stage,” said Rosenstiel.
The coagulation cells also explain why Covid-19 patients ultimately die of thrombosis, pulmonary embolism and numerous blockages of many small vessels. Rosenstiel hopes to find possible approaches for therapies by analyzing the coagulation, among other things. It may be that the immature platelet progenitor cells are not the same under Covid conditions as under influenza conditions or in other infections: “We have seen that these megakaryocytes clot more because their energy metabolism is different from the normal megakaryocytes. We’re trying to track that, because we can use that to treat the long-term consequences of Covid-19. “
There are many indications that the fight against a difficult course is a fight that will be decided early on with Covid-19. Antiviral drugs or high-dose antibody therapy with the blood plasma of people who have already suffered an illness and who also have a lot of antibodies – a very high titer – only work if they are used before the severe course begins: ” Only if you discover the disease early and treat it early will you be lucky in an accident, so to speak, “explains Valipour. “If you only come after seven to ten days, when the initially mild complaints have turned into severe complaints, you can neither treat with antiviral drugs nor with antibody therapy. Then it is usually too late, there are already so many mechanisms in place Bodies have been triggered that are difficult to stop. “
Elisabeth Puchhammer-Stöckl, a virologist at MedUni Vienna, is looking for therapeutic approaches that prevent the virus from multiplying in the body. “We have to identify the genetic markers or other situations in the interaction between the virus and human cells that ensure that the virus can reproduce better or cause more damage,” she says.
Puchhammer-Stöckl has recently come one step closer to this goal. She was able to show that the lack of a certain receptor on the natural killer cells (NK cells) favors a severe course. The NK cells are among the first to respond to infection. If their receptors are impaired, this first immune reaction is already too weak. For genetic reasons, 34 percent of the Austrian population have the receptor insufficiently or not at all.
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