Many of the severe courses of Covid-19 are associated with thrombosis and pulmonary embolism. Apparently, the coronavirus mainly attacks the inner walls of the blood vessels. With extremely far-reaching consequences.
Patients who have difficulty breathing due to lung damage and whose blood oxygen saturation is well below the normal values of 94 to 98 percent: At first glance, it seemed logical to see Covid-19 as a respiratory disease. But after more than a year of a pandemic and millions of sick people worldwide, it is clear that this disease cannot be categorized that easily.
“Even in the first phase of the pandemic, publications came out that many of the severe courses are associated with the occurrence of thromboses and pulmonary embolisms,” remembers Markus Steinbauer. “That prompted us to say back then that we do not have a respiratory illness here, but that we probably have an illness that leads to damage or thrombosis in the vascular system via unclear mechanisms,” says the chief physician at the Clinic for Vascular Surgery at the Barmherzige Brüder Hospital in Regensburg in conversation with ntv.de.
Only which mechanisms these are was still quite unclear in spring 2020. In many Covid 19 patients, the treating doctors saw complications in the blood vessels, such as pulmonary embolism, severe circulatory disorders in the legs and arms, or strokes. “As early as April 2020, for example, the D-dimer was an important prognostic parameter for a severe course of the disease,” says Steinbauer. This is a laboratory test that usually indicates the occurrence of vascular disease or thrombosis. “We already knew that when the D-dimer is high, the patient goes to the inpatient more often and needs intensive treatment more often,” says Steinbauer. As a result, anticoagulants were included in the medication. Since the summer of 2020 there has been a recommendation to use thrombosis prophylaxis even in patients who are already showing a more severe course on an outpatient basis. These drugs were given in higher therapeutic doses for those patients who had to be hospitalized because of severe symptoms. Among other things, these measures, which are otherwise taken in cardiovascular diseases, according to Steinbauer, reduced patient mortality considerably.
Inflammation in children
Another lead pursued by the doctors came from special disease developments in children. They showed vascular inflammation in the skin, heart, gastrointestinal tract, mucous membranes, lungs, liver or kidneys, which are otherwise more likely to occur in autoimmune diseases. Initially, these symptoms were linked to Kawasaki syndrome. They are now classified as MIS-C, derived from the English term “Multisystem Inflammatory Syndrome in Children”.
In the meantime, the corona viruses have also been detected in the endothelium, i.e. the inner skin of the blood vessels. The endothelium fulfills an important protective function. It produces necessary components that are needed for human blood clotting, plays an important role in inflammatory processes and helps to form new blood vessels. In addition, endothelial cells regulate the exchange of substances between vessels and tissue as well as the vessel width, which influences blood pressure, writes vascular medicine Sven Hausen in a specialist article. According to Steinbauer, this was the point at which it became clear: “The virus does not only work in the lungs, but in the entire body.” And it can be extremely destructive.
The knowledge gained up to then mostly had an impact on the treatment of Covid 19 patients, which has been continuously optimized over the past few months. In the Barmherzige Brüder hospital in Regensburg, this has reduced the mortality rate of patients treated in intensive care units from around 50 percent to 25 to 30 percent of patients, Steinbauer estimates. The findings also changed our understanding of the disease. This also makes it clearer why smokers, people with high blood pressure or poorly adjusted diabetics belong to the special Covid risk groups. They all already have a basic risk for vascular health.
The initially puzzling symptoms that occurred in all parts of the body can also be explained by the findings, because the blood vessels run through the entire body. If the virus spreads along the endothelium, it can lead to generalized vascular inflammation in patients: endotheliitis. It is possible that some long covid symptoms can also be explained by damage to the vascular system. This conclusion is made by a Study by scientists working with Florence WJ Chioh from Singapore close, which demonstrated increased levels of circulating endothelial cells, so-called CECs, in the blood of recovered Covid patients. They suspect that an overactive state of the immune system that persists even after recovery may be the reason. CECs are a sign of the endothelial dysfunction that is associated with many vascular diseases, such as myocardial infarction, stroke, the accumulation of plaques in the inner walls of the blood vessels and vascular inflammation.
Again new questions
Researchers from the United States and China are therefore in one place Article published in the journal “Circulation Research” on the assessment that Covid-19 is a vascular disease. Because Sars-CoV-2 attacks the vascular system at the cellular level and damages it. Many vascular experts, including Steinbauer, share this classification.
However, as is so often the case with Sars-Cov-2: Every clear finding is connected with further questions to which there is still no answer. In the case of the US and Chinese researchers, it is the fact that the “pseudovirus” they created was surrounded by the classic Sars-CoV-2 crown of spike proteins, but did not contain an actual virus. Nevertheless, it led to damage to the lungs and arteries in the animal model. Tissue samples also showed inflammation in the endothelial cells. Scientists see this as evidence that the spike protein alone is enough to cause disease.
According to Steinbauer, the paper primarily provides an answer to how the inflammatory processes in the endothelium come about – apparently through the action of the spike protein, which damages the cells by binding to the ACE2 receptors. The angiotensin-converting enzyme 2 is mainly produced by cells in the lungs, where it can serve as an entry point for the virus on the cell surface. That would explain why the damage was first visible primarily in the lungs of Covid 19 patients.
The physiological function of ACE2 is to break down the blood pressure-increasing hormone angiotensin I. By damaging the binding to the ACE2 receptor, the spike protein disrupts the corresponding signal transmission. The information about which vessel widths have to be regulated is no longer correctly passed on. It seems to behave in a similar way with the coagulation parameters in the blood.
Different coagulation parameters
For Steinbauer, however, it is still unclear whether the thromboses in Covid patients “can now be attributed to disorders of the plasmatic coagulation or are to be sought on the cellular level with an effect on the endothelium”. Existing study results also come into play here. For example, patients who were already taking ASA as an anticoagulant because of cardiovascular diseases showed less severe courses of Covid than those who did not take ASA.
However, ASA acts on the platelets in the blood, i.e. influences the cellular blood coagulation response by attaching and sticking the blood platelets to a damaged endothelium. “The clinically more frequent thromboses and embolisms in veins, however, are to be assigned to the plasmatic side,” observes the Regensburg vascular expert. The coagulation is controlled by proteins that are in the blood. And there is still insufficient research into how the coronavirus intervenes in this process.
“We have to find out what happens at the molecular level. If you find out, you may have clues as to how certain signal chains are triggered and possibly trigger the onset of the disease,” says Steinbauer. After further research, this could be interrupted with drugs or molecular biology.
Consequences for vaccination?
And one more question arises after the study. If spike protein alone can cause harm, what does that mean for vaccines that use spike protein to “teach” the human body about the coronavirus? Georg-Christian Zinn, director of the Bioscientia hygiene center, said at ntv: “Of course, there is still a virus attached to these spike proteins, which together with the spike proteins causes cell damage.” It normally only takes “a few hours to days” for these spike proteins to be broken down. In addition, the proteins were only distributed relatively locally in the puncture site. Sometimes there is also a transport to the adjacent lymph nodes. “You can tell after the vaccination by the swellings, which are a little painful.” However, it is not intended that the spike proteins scatter throughout the body. And that is also not necessary to induce an antibody response, explains the infectiologist.
So far it is only certain that the spike protein already causes damage. But it is still unclear what these are. The Chinese and US scientists hope to be able to next examine the mechanism by which the destroyed ACE2 protein damages the mitochondria, the organelles that generate energy for cells, and causes them to change their shape. Then they want to gain new knowledge about the infectivity and severity of mutated coronaviruses with further studies on mutated spike proteins.
Researchers around the world are now entering the next round with their questions. “The question is, which problems are most relevant for patients in the long term,” says Steinbauer. In a patient with lung failure, the respiratory problems would be in the foreground. Patients with pulmonary embolism or problems with blood vessels should be provided with the best possible vascular medicine.
– .
