State of research: Where does Corona come from and what happens next?

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The American science magazine nature has summarized the state of research on corona viruses in an overview article.

According to this, the virus probably got from bats to humans via an intermediate host. The mechanism of action of the virus in the human body is now also relatively well understood.

With regard to the future developments of the virus, there is a realistic, an optimistic, and a pessimistic forecast.

108 years ago, German veterinarians examined a cat with a fever and a swollen stomach. At that time, the scientists could not diagnose what the animal was suffering from. However, based on the examination protocols that have been handed down, doctors today can say that this was possibly the first documented case of a coronavirus disease.

At the time, little research was being done on animal diseases in particular. Whole livestock died again and again and showed the most varied symptoms: chickens seemed to suffer from bronchitis, piglets from persistent diarrhea.

It was only in the 1960s that US researchers and their British colleagues were able to isolate two viruses that had caused cold symptoms in humans. Observed under the microscope, however, they showed great similarities to the unknown viruses that the various animal diseases had caused.

Their spherical surface is studded with “spikes” made of proteins. They are reminiscent of the sun’s corona, which looks like a wreath of rays when viewed from Earth. The virus type was therefore christened Corona, according to an overview article in the US science magazine nature, which summarizes the current state of research on corona viruses.

Science is only slowly beginning to understand these viruses

It quickly became clear that the viruses could develop very dynamically and, for example, suddenly jump from dogs to cats, only shortly afterwards to cause particularly bad symptoms in pigs. For a long time, however, it appeared that this virus type caused at most mild symptoms similar to colds.

Only the outbreak of Severe Acute Respiratory Syndrome (SARS) in 2002/2003, which killed 800 people worldwide in a short time, showed that these viruses can also mutate in such a way that they become dangerous to the human organism.

Many different strains of corona are known today, but only seven of them can also infect humans. Four of them cause the typical cold symptoms that scientists have observed for a long time. The other three, on the other hand, sometimes trigger serious to fatal diseases: SARS, the Middle East respiratory syndrome MERS and currently Covid-19.

The coronavirus SARS-CoV-2, which has killed 318,596 people to date (May 19, 2020), is by no means fully understood. The global scientific community is researching the virus at high pressure, but neither its biological origin, the mechanism of action of the virus on the human body and the expected future developments have so far been fully understandable for science. But slowly the pieces of the puzzle come together.

Origin: The virus must have come to humans through an intermediate host

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What is certain is that SARS-CoV-2 shares 69 percent of its genome with an animal corona virus that was found in bats in a cave in Yunnan, China. This suggests that the virus may have come from there – but there must have been an intermediate host. The virus must have been mutated. How exactly that happened and who was the intermediate host is still unclear.

Because the virus found in the bats is harmless to humans: the cells of bats differ from human cells, and the original virus cannot penetrate human cells. The so-called spike proteins of SARS-CoV-2, on the other hand, have a section – the so-called receptor binding domain (RBD) – that enables the virus to penetrate human cells particularly effectively.

Mechanism of action: The course of the disease depends primarily on where the virus enters the body

For a long time it was puzzling why SARS-CoV-2 causes so differently difficult courses in humans: From those who do not even notice the disease to those who die of it within days. However, science now understands this better.

With its sting proteins, the virus binds to a biomolecule called ACE2, which is located on the surfaces of almost all body cells from the lungs to the blood vessels. Once it has entered the cell, the virus forces the cell to reproduce its genetic make-up. This creates new virus particles that again infect new cells.

The decisive factor for the course of the disease is how many of these pathogens the body has to deal with at the same time. “If ten virus particles reach us from the cough of a person further away, they could trigger an infection in the throat,” explains pathologist Shu-Yuan Xiao from the University of Chicago in the science magazine nature. “However, the cilia found there will probably do their job and quickly eliminate the intruders.” However, if a person infected from close up coughs 100 virus particles in the direction of another, some of them may make it directly to the lungs.

Read also: Not only cough and fever: the virus is able to attack almost every area of ​​the body – what doctors now know about Covid 19 symptoms

This also explains how the disease can paralyze the sense of taste and smell: in these cases, the infection begins in the throat and nose. The saliva produced there is then contagious and can be transferred to others by droplets or from there it reaches your own lungs.

However, the body manages to stop the infection in the throat in some cases, so that in these cases the disease proceeds without other typical symptoms such as difficulty breathing. In yet other cases, however, the pathogen reaches the lungs directly at the beginning and causes dangerous breathing problems there at an early stage.

The immune system sometimes reacts appropriately, sometimes not at all, and sometimes it overreacts

After infection, most people automatically form antibodies that connect to the virus and prevent it from entering new cells. If this happens quickly, these people will show little or no symptoms.

However, the immune system of some people is apparently unable to produce sufficient antibodies. In these cases, SARS-CoV-2 destroys the alveoli – the tiny sacs in the lungs that carry oxygen from the air we breathe into the blood. This leads to the severe and potentially fatal course that requires ventilation.

At this point, too, a targeted immune response from the body can often stop the disease on its own. But in some people the immune system then overreacts: it causes a so-called cytokine storm, which exacerbates the tissue damage.

The cause of death is usually a pulmonary embolism, but the virus can damage almost all organs

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However, only a few die immediately from this inflammatory reaction. Pulmonary embolism appears to be the cause of this much more frequently: a blood clot in the lungs.

The researchers suspect that the organs infected by the viruses excrete blood-clotting substances in an overreaction. These clump the blood and create dangerous clots that often initially appear in the veins of the legs (thrombosis).

At some point, however, they can detach themselves there and are pumped with the blood into the heart and lungs, where they clog small vessels. The result is chest pain and shortness of breath. In extreme cases, such a clot then causes the organs to fail and ultimately leads to death.

Most of the time, the lungs or heart fail, but because the ACE2 molecules are found in almost all oranges and the virus circulates throughout the body through the blood, damage to the kidneys, liver, spleen, brain and intestine can also occur. The pathogen has now even been discovered in sperm. Read Too

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Future developments: from optimistic to realistic to pessimistic

However, the more important question is what the future looks like with the virus. There are three options: realistic, optimistic and pessimistic. The realistic possibility is also the most probable: people learn to live with the virus by fighting it either with vaccinations and medication – or with their own immune system.

However, science faces challenges in drug development. Coronaviruses have a peculiarity: Antiviral drugs such as ribavirin, which are often used, stop the spread of viruses by causing mutations that deactivate the pathogen. But corona viruses have a kind of correction mechanism that in turn deactivates such mutations. Therefore, many otherwise effective drugs are probably useless with SARS-CoV-2.

Does the human immune system automatically develop adequate protection against the virus?

But people could also win the fight against the virus through their own immune systems. In conversation with nature, epidemiologist Klaus Stöhr from the World Health Organization (WHO) outlines this scenario as follows. “The most likely scenario is that the virus will spread further and will affect most of the world’s population in a relatively short time.”

So many people worldwide will get the virus and also die from it, but soon enough people will have developed enough antibodies against the pathogen as a result. Like the four mild coronaviruses, SARS-CoV-2 would then become a permanent companion for mankind, but which would then only cause cold-like diseases, Stöhr continued.

For this reason, he believes that a vaccine will not be necessary. However, this theory is contradicted by many other experts who believe that only a vaccine can end the pandemic.

The optimistic forecast assumes that the natural mutation of the virus could weaken it

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The optimistic prognosis assumes that the natural mutation of the virus could play into human hands. Viruses often rearrange their genetic material and exchange pieces of their RNA with other corona viruses. When two viruses meet, new types of variants can emerge that can infect new cell types – or else other species.

Some researchers are now hoping that SARS-CoV-2 will adapt better to humans through such natural mutations – and weaken itself in the process. While there is a risk that the virus will become more contagious and can dock onto new cells even more easily, it could be less fatal.

This probably already happened in a similar way with the so-called OC43 corona virus. Today it is one of the four corona strains that cause mild cold-like symptoms in humans. But that was not always the case, as virologists at the Belgian University of Leuven found out.

At first he mainly affected cows, but he mutated around 1890 and suddenly became infectious to humans. In the years 1889 to 1890 there was a worldwide pandemic with more than a million deaths. At that time, science suspected that it was a particularly severe outbreak of influenza.

From nature’s point of view, however, there is no evidence that something similar could happen with SARS-CoV-2, so that this optimistic future version is rather unlikely.

In the worst case, the natural mutation of the virus could also harm humans

There is still a danger in the case of immunity due to the formation of antibodies as well as in the development of a drug or a vaccine: In principle, the virus can mutate to our disadvantage.

If it mutates too quickly, protection against renewed viral disease with antibodies – which those who have already had an infection have so far enjoyed – could lapse.

Above all, however, the history of corona viruses shows that the innumerable strains of the virus that occur naturally can, at least in theory, mutate at any time and spread to humans. Corona viruses of one form or another will therefore continue to accompany people for a long time.

“More will happen,” predicts evolutionary biologist Andrew Rambaut from Edinburgh University in an interview with nature; “Either it’s already doing it out there, or it’s in the making.” Read Too

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