A Swiss researcher gives hope in the fight against the pandemic

As of Friday evening in Germany are around 4200 People died who were diagnosed with Sars-CoV-2 infection. It is known that mostly older patients, who already had previous illnesses such as chronic high blood pressure, other cardiovascular or respiratory diseases, have a severe, life-threatening course of Covid – 19 – disease.

But what is the cause of death in the end?

And why do young, healthy people die from the consequences of the infection?

At present, there is growing evidence that not only the so-called “shock lung”, the acute respiratory distress syndrome (ARDS), is causing death, but rather pulmonary embolism – that is Blockage of vital pulmonary vessels with blood clots.

That is a “hard-founded suspicion”, says Nils Kucher, angiologist and cardiologist at the University of Zurich and specialist in thrombosis and pulmonary embolism.

What are the indications that Covid – 19 – Deaths caused by pulmonary embolism?

“The first time I stopped when we had to find out that from the over 1200 Deaths in Switzerland with eight million inhabitants, the vast majority, probably 75 percent, not at the hospital, but at home dies, ”says Kucher.

Many Covid – 19 – Diagnosed patients sent home in quarantine due to an initially harmless or mild course, would at best get a few pain and antipyretic medications.

But apparently many would no longer be able to trigger the emergency call if the Covid – 19 – disease suddenly worsened and led to severe inflammation of the pulmonary vessels, blood coagulation and ultimately fatal pulmonary embolism. “In New York many Covid die in the clinics – 19 – patients, but most of the dead will probably be picked up from home. ”

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Whether there are more people in domestic quarantine with Covid in Germany – 19 die than in intensive care units, is unclear. “We cannot say with certainty whether the patients died at home or in the hospital,” Susanne Glasmacher, spokeswoman for the Robert Koch Institute, answered a Tagesspiegel request. Information was only available for “a part” of the deaths as to whether they were hospitalized on the day of death. The ScienceMediaCenter Germany counts in this category 1806 deceased.

For some deaths, the RKI spokeswoman said that they had not been hospitalized, “but this information is not very reliable, because the patient may be admitted to the hospital When the report was not hospitalized, but were later hospitalized, which was not recorded in the reporting system. ”

What is known about Covid's causes of death – 19 – Victims?

Neither has the RKI known until now what is decisive for the death of the Covid – 19 Patient was. “Nor can we provide detailed information on the cause of death,” says Glasmacher. The health authorities get the mortuary certificates of the deaths, but it is not easy to determine the exact cause of death.

“The doctors determining death form a causal chain of the causes leading to death on the mortgage certificates. These will be validated later and evaluated in the cause of death statistics. ” According to this, the course of the disease is different – for some the infection leads to acute lung failure, shock lung, for others to myocarditis, for others to multi-organ failure.

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But according to Kucher, one cause of death has so far hardly been considered: pulmonary embolism. This is because patients with Covid – 19 are rarely examined using imaging techniques such as computed tomography (CT).

“Die Covid – 19 – Patients who are already in the intensive care unit are only rarely scanned because of the risk of infection, ”says Kucher. So of around 1000 patients who were in Wuhan treated and described in one study, only 25 get a CT. But if this was done, pulmonary embolism would be discovered in many cases. In the Chinese study it was 10, almost half of the patients examined.

In a study at two university clinics in Holland, the researchers found 18 percent of Covid – 19 – patient clot. In a clinic in Milan under 388 Covid – 19 Patients discovered in almost eight percent pulmonary embolism. But there are certainly a lot more because in the Milan clinic it is only in 10 percent of all Covid – 19 – patients who gave examinations for the detection of embolism , says Kucher.

“If you only look at the cases in which such imaging diagnostics were carried out , then found themselves in 36 Percent pulmonary embolism – and that's a lot, ”says Kucher. The study, in which the specialist originally from Brandenburg is involved, is expected to be published in the Thrombosis Research Journal next week.

Ein behandelnder Arzt zeigt auf die CT-Aufnahme der Lunge eines Patienten, der sich mit dem Coronavirus infiziert hat.

A treating doctor points to the CT scan of the lungs of a patient who has become infected with the corona virus. Photo: dpa / Remko De Waal

Beyond reporting the doctors in Milan and meanwhile also some press reports in the Italian fields of young Covid – 19 – Patients who died in quarantine at home and whose autopsy showed they had fatal pulmonary embolism, says Kucher.

However, according to the RKI, “only a few deaths are autopsied”. If so, then Kucher's suspicion is confirmed: “Unusually many thromboses and pulmonary embolisms”, Klaus Püschel, for example, discovered the director of the Hamburg Institute for Forensic Medicine at the Eppendorf University Hospital.

How could pulmonary embolism in Covid – 19 – Patients prevented?

Kucher now wants to start an “emergency study” at the end of next week, which has already been submitted to the Ethics Committee of the University Hospital Zurich and has been classified as urgent.

The half of 1000 Covid – 19 – patients over 50 Years who are sent into quarantine due to mild or mild symptoms should inject a blood thinner (Clexane) every day for two weeks to prevent blood clots, the other half will get it usual treatment without thromboprophylaxis.

So far, such an outpatient thrombosis prevention with Covid – 19 – patients without additional risk factors not recommended and probably not administered in most cases , since there is a certain (albeit slight) risk of bleeding, which is why blood thinners are practically only given in the clinic. Clexane, an inexpensive blood thinner based on heparin, can reduce the risk of thrombosis by 70 Reduce percent.

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Kucher is convinced that “if we get Clexane early that we can then prevent the severe coagulation disorder that triggers this virus and possibly reduce mortality ”. According to previous experience in Switzerland, 15 percent, every eighth study patient with severe complications from home quarantine are transferred to the clinic or (6.5 percent) die.

It is still no more than a “reasonable suspicion” that Covid – 19 – Patients also or especially die from pulmonary embolism and patients could escape this fate with early administration of blood thinners. The reason is at least plausible.

Because the viruses primarily attack lung cells because they usually get into the body via the lungs and their natural docking points, the ACE-2 receptor, are the most common on the lung cells are represented. But the gateway ACE-2 can also be found on the inner skin of blood vessels, the endothelial cells.

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Once the virus has damaged the alveoli to such an extent that it gets into the bloodstream, it also infects the endothelium and inflames the blood vessels yourself strong. This leads to the release of large quantities of messenger substances, cytokines, which on the one hand alarm the immune system but also activate the blood coagulation cascade. And extremely.

“We measure high concentrations of blood coagulation factors such as fibrinogen and its cleavage products, the D-dimers,” says Kucher. This ultimately leads to thrombosis and pulmonary embolism. Block important vessels.

The patient dies. And quickly – just as a stroke or heart attack can quickly lead to death. “My hypothesis is that many are no longer able to start the emergency call because they are suddenly feeling so bad,” says Kucher.

When should the results of the study be expected?

Kucher would also like to examine the genetic makeup of patients or other biomarkers to finally be able to say whether some of them are more prone to pulmonary embolism than others because of their genetic predisposition. Especially with the genes that control the blood coagulation cascade, there are many variants that sometimes lead to faster, sometimes to slower coagulation.

This could not only explain why some young, apparently healthy infected people suddenly die, while some 80 – year-old shakes off the viruses harmlessly. Knowledge of such biomarkers could also tell doctors in advance which patients should take blood thinners and which should not.

“But unfortunately we have to do without that,” says Kucher. For lack of money. There is no public research funding. The Swiss National Science Foundation, the equivalent of the German Research Foundation, has the money for Covid – 19 – Research already distributed at the end of March.

And the requested pharmaceutical companies that manufacture these blood thinners have shown no interest in the emergency study to support financially. In addition, many approved blood thinners such as Clexane are no longer patent-protected. “This means that we largely pay for the study from our own research funds,” says Kucher.

But it was worth it: “The most important task now is to find out whether we have the rate of hospital stays and the high mortality rate from Covid – 19 with a simple measure, ”says Kucher. “It would be possible that if we prevent these thromboses, the coronavirus is no longer as dangerous, that's my hypothesis.”

So the specialist for pulmonary embolism and thrombosis is convinced of it, so clearly warns against it, already with all outpatient Covid – 19 – patients to perform thrombosis prophylaxis. “We have to study safety and effectiveness first.” So whether the blood thinner at Covid – 19 – Patients may trigger undesirable side effects such as bleeding or reduce mortality too little for side effects to be acceptable.

And it may also be that the current Clexane dosage is not sufficient because Covid – 19 the blood clotting so intensified. All Swiss university clinics within 12 hours of your study participation. “That has never happened before,” says Kucher.

And if German clinics would also participate, the study could produce valid results in a few weeks. Ideally, the world could then quickly have a cheap, already approved agent available that a large part of the Covid – 19 – could prevent death and curb fear of the pandemic.