Part 3 Review of the year of the coronavirus: the genetics of the disease, its effects and the search for its origin – knowledge

Twelve months in which we got to know the virus: Never before has science learned so much about a new type of pathogen so quickly. But we still know far too little. In a three-part chronicle, we trace the progress made in knowledge about the Sars-CoV-2 and Covid-19 coronavirus.

In this third part you will read the months from September to December in which important progress was made in the fight against the pandemic. Part one with the months from January to April can be found here. Part two with May to August here.

SEPTEMBER: Genes help determine who is seriously ill with Covid-19

With Covid-19, it became apparent early on that, in addition to old age, there are other risk factors for a severe course: male gender, obesity, the previous illness diabetes and high blood pressure. These characteristics have foundations in the human genome. And there are other genetic factors that are less obvious, but can make the difference between a mild and a fatal course.

At the end of September, researchers reported in the science journal “Science” that severe courses can be related to weak points in the patient’s immune system. A number of genes are involved in the reactions that take place when pathogens attack the organism.

This includes genes that contain the building instructions for interferons. These substances are involved in the control of the body’s defenses. When pathogens are detected, they call the immune system on the scene. Two research teams led by Jean-Laurent Casanova from Rockefeller University will start looking for young people around the world who are seriously ill with Covid-19 as early as February. They examine the genetic make-up of more than 3,000 people affected for changes in interferon genes.

Read our other parts of the review of the year of the coronavirus:

It turns out that at least 3.5 percent of those severely infected with Covid-19 have altered, mutated variants of interferon genes. Genetic traits can determine the clinical course of the infection, the researchers conclude.

Models: The shell of Sars-CoV-2 is covered with spikes with which the virus docks on human cells. The spike or …Photo: AFP

The fact that the lack of interferons can make the organism more susceptible to Sars-CoV-2 leads to the assumption that other seriously ill people also do not have interferons, even if the coding genes work. In more than ten percent of the study patients, the team found antibodies in the blood that are directed against the body’s own substances.

The antibodies block two types of interferons and are undetectable in patients with mild courses of the infection and in healthy people. Almost all of the patients with the harmful antibodies are men.

Causes could be changes in genes on the X chromosome, of which men only have one copy. Women have two, so if one chromosome is defective, the other can take over. The study also explains one reason why men are more likely to become seriously ill than women.

OCTOBER: The constantly mutating virus

Since the beginning of the pandemic, researchers have been tracking how Sars-CoV-2 is gradually changing. As with every virus, new variants are constantly being created, with every multiplication in an infected person. They differ through mutations in the virus genome. Researchers use this fact like a genetic fingerprint.

Using the genetic signature of the viruses that were circulating in the Austrian ski resort of Ischgl, for example, they can track the countries to which they were taken with the returning ski vacationers. If the “Ischgl signature” suddenly appears in Norway, it is clear where the virus comes from, even without the ski holidaymaker’s knowledge.

Most mutations do not change the properties of the virus. So the variants do not infect people more easily or make them sicker. But in October researchers became nervous for the first time when it became known that Sars-CoV-2 had jumped from humans to minks in the Netherlands and Denmark. There the animals are kept for fur production and probably got infected by their breeders.

Interactive map

Mutations accumulate in the course of such host changes. In fact, five changes were found in the genetic make-up, including two in the gene for the important S protein – the “sting” with which the viruses penetrate the cells. But experts ruled out that this virus variant, which is no longer circulating, is more infectious or otherwise more aggressive for humans.

This is apparently different with virus variant B.1.1.7, which has been circulating in Great Britain since at least September 20. Within a few months, it has spread faster than other varieties in Greater London and the south and south-east of Great Britain. This can also be the result of a series of superspreading events. However, according to analyzes, it could also be related to an actually increased infectivity of the variant. The variant has now also been proven in Germany.

A higher infectiousness can lead to more diseases and thus more deaths. But the British virus variant – and a similar but unrelated one in South Africa – can be contained using the same hygiene and distance rules as the original Sars-CoV-2. In addition, the vaccine manufacturers Biontech and Moderna assure that their vaccines also protect against this virus variant.

First vaccinations: In the USA, an emergency doctor is vaccinated with the preparation from Pfizer-Biontech.Foto: Brian Snyder/Reuters POOL/dpa

NOVEMBER: What the vaccines target

In November something is becoming more and more likely that was still considered almost impossible in April: Vaccines tested according to the highest standards – unlike the early use of the Russian “Sputnik V” – could be approved this year

Warnings had been heard over and over again over the year. Despite all the pressure, no shortcuts should be taken in clinical trials. In addition, even in the early test phases, promising vaccines could disappoint in the crucial phase 3 of the clinical trial or show unacceptable side effects. In addition, there was mixed skepticism in view of the rather one-sided molecular objectives of the vaccine inventors.

Almost all of them concentrate on a single characteristic protein in the virus envelope. That “spike” – or “S-protein” for short, is only one of four such protein structures that give Sars-CoV-2 an appearance that is potentially recognizable for the immune system. Against another of these four, called N-protein, even significantly more antibodies are usually produced, although it is actually more hidden in the virus envelope.

This mystery is also a reason why almost everyone is concentrating on the comparatively huge S protein – despite isolated warnings from experts that the virus could mutate precisely on the S protein. Vaccines that were based only on its originally known versions could thus be less or no longer effective.

Now, towards the end of the year, it turns out that the focus on the large molecule, which is clearly visible to immune cells and antibodies, was apparently justified. The data from the most advanced studies with vaccines from AstraZeneca, Moderna and Biontech-Pfizer show high protective effects.

Nevertheless, the fear that mutations could affect the spike protein is also confirmed. This is because, even without a vaccine, this is crucial for the ability of the virus to infect cells. A viral “innovation” that makes the S protein more effective and the virus more infectious has a good chance of catching on. The new variants, which will be known from Great Britain and South Africa in December, differ precisely here, among other things.

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There is currently much to suggest that the vaccines will remain effective against these as well. However, this does not necessarily have to apply to other mutations that may occur or have long been in circulation. This is one of the reasons why, despite the vaccine, attempts must continue to be made to hinder the spread of the virus as much as possible.

Because even a highly dangerous mutated virus only has a chance of spreading if you give it the chance. If it only sits in people who are well insulated and who do not infect anyone, it can completely disappear again. And even if a variant against which the vaccines are less effective should spread, it would be possible to adapt the vaccine. And with the N-protein, for example, there are now new findings that could help develop vaccines that are not solely dependent on that one molecular target.

This now-closed seafood and wildlife market in Wuhan is believed to be the origin of the pandemic.Foto: imago images / Kyodo News

DECEMBER: The origin of the pandemic

The tracks lead to Wuhan. The health authorities of the capital of the Chinese province of Hubei reported an accumulation of pneumonia on December 31, 2019. The World Health Organization (WHO) picks up the news and on January 5th, the virus, later known as Sars-CoV-2, is on the growing list of new pathogens that can infect people with a publication in the specialist journal “Disease Outbreak News”.

Some of the first to fall ill are people who regularly visit or work at the Huanan wholesale market. At the market, seafood, but also wild and farmed animals, are sold live or slaughtered or prepared for consumption. The virus could have jumped from one of the animals to a human in the market. Samples taken on the premises as late as December will test positive for Sars-CoV-2, which is another clue to the market as the source of the outbreak.

But there were early doubts about this theory because not all patients were on the market. In addition, genetically different variants of the virus are described as early as January, the common ancestor of which must have existed earlier. It seems plausible that someone who was infected elsewhere first brought the virus to market. Further search for clues on site would be helpful. But the market will be closed on January 1, 2020, and the site will be cleared and disinfected.

Knowing where a pandemic started is important in order to prevent further contagion from people down the same path. It also helps to understand how outbreaks develop and how best to respond to them.

Genetic research shows that Sars-CoV-2 is closely related to coronaviruses that are common among horseshoe bat bats. A large number of variants have now developed through mutations, but originally the viruses are very similar to one another. This points to a single event in which it jumped to the new host human at the end of 2019. The carrier was probably not a bat, but an intermediate host such as larvae roller or raccoon dog.

A WHO expert commission is to investigate further exactly how it happened. But due to political tensions between China and the USA, a lot of time is wasted. The team, with expertise in epidemiology, virology, and veterinary medicine, will begin in Wuhan and then expand its search to include, for example, the routes by which wild animals get to the market. The first lesson from the venture should be to confirm that it is helpful to start searching early.

Another finding: in order to limit the risk of zoonoses – i.e. animal diseases that spread to humans – people have to be more careful in their dealings with animals and their natural habitats. The closer the contact between humans and wild animals, the further people penetrate into the habitats, the more likely it is to jump over.

In the last few decades the WHO has recorded an increasing number of new zoonoses, two out of three new diseases belong to this group. Bird flu, Ebola, influenza, leprosy, Lassa fever, Mers, rabies, Sars, tuberculosis, Zika fever are well-known representatives. At the end of the year, WHO chief Tedros Adhanom Ghebreyesus issued another urgent warning: If we continue as before, Covid-19 will only be the beginning.

Part one with the months from January to April can be found here. Part two with May to August here.

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