The coronavirus epidemic develops into a pandemic

Here are all the latest scientific data about this in recent days

The number of cases of infection with coronavirus infection is growing. The number of sick outside China catches up with the indicators in the country where the virus arose. The medicine and the vaccine have not yet been found, but scientists managed to find out more about the source of the virus, its internal device, potential mortality and asymptomatic transmission cases. Medusa says that it has become known about coronavirus in recent days.

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What has become known over the past month

Pandemia: Already or not yet

The main thing that happened with the new coronavirus infection in recent years is the transition from the local to the global level: the number of cases outside of China rapidly catching up with the number of cases in China itself, and this happens in various countries. All this causes debate about whether the outbreak of infection has passed to the pandemic stage.

At the press conference held in Geneva on February 24, the head of the near Tedros Gebreisus stated that it was too early to call the outbreak of a new coronavirus infection, that is, the global epidemic. “Now we do not see evidence of the uncontrolled distribution of coronavirus, as well as we do not see a significant number of heavy and lethal cases on a global scale,” he explained his position. - Does the virus have the ability to cause pandemia? Absolutely. Is this already happening? According to our estimates, not yet. ”

The press conference took place just after information on large-scale outbreaks of coronavirus infection in Italy and South Korea, as well as several deadly cases in Iran. After that, new countries began to appear in each of the daily WHO reports, where cases of disease were recorded. At the moment, the episodes of infection with a coronavirus infection have been registered on all continents except Antarctica, and the recorded number of new sick people outside China for the first time exceeded Chinese values.

Neither the Epidemic nor the Pandemia have unambiguous formal criteria, but against such an information background, refusal to call the global spread of pandemia's infection does not seem quite sincere. In any case, many scientists believe that the outbreak has already passed into the global stage, and it will not work to restrain it. This was most clearly expressed in a conversation with Nature by a Harvard epidemiologist Mark Lipsich: “Whatever WHO says, I believe that all epidemiological conditions for the pandemic are met. Whatever reasonable definition of this concept we accept, we will have to admit that we are now observing the pandemic. ”

Source

In disputes about the natural source of the virus, scientists today were at the same point with which they started two months ago. The performances passed a full circle: from bats , which were originally considered the most likely natural tank, through snakes and Pangolinov , and back to bat.

"Medusa" already wrote that the snakes were called as a source of the virus as a result of a rough error. A similar, but another story happened with the Malaysian Pangolins: scientists correctly determined that the Pangolin coronaviruses are quite similar to the new Sars-Cov-2 virus (it used to be called 2019-NCOV). They also found that one fragment of the viral S-protein (with which the virus is connected to the owner of the owner) in the Pangolins viruses almost coincides with the human virus, differing in one single amino acid replacement. However, one group of co -authors of this loud article, as it turned out later, misunderstood another group - as a result of which almost complete similarity in a particular fragment of one protein turned into an almost complete similarity of two different viruses. And, as a result, in a pangoline theory. In fact, the RNA of Pangolin coronaviruses coincides with human only by 90.3%, which is significantly less than 96% of the similarity of coronavirus of bats and those 99.8% of the similarities that allowed to determine the intermediate host in the case of the torso/SARS (“atypical pneumonia”).

The existence of very similar coronavirus among the steamed people and even the infection of people living in the habitats of these animals does not cause scientists in doubt. This is a well -known fact, carefully studied by Chinese virus, primarily Shi Jenley from the Ujan virology Institute. The disputes that lasted for two months concerned not so much this natural hearth as the nature of the direct carrier in the Ulyan market - the very animal that infected the first patient. In the case of the previous coronavirus epidemic, the torso/sars (“atypical pneumonia”) turned out to be wild cetettes by this intermediate host, although bats were the main natural reservoir, as well as for the new virus. The determination of the intermediate host can help prevent the re -transfer of the virus from animals, although it may no longer make sense: on the wave of an epidemic of the coronavirus, China prohibited the sale of all wild animals.

Virus

The main data that were known about the biology of the virus itself by the beginning of February, when there were only three dozen genomes, remain correct today, when there are already 119 .

All the isolates of the virus are very close - which means the transition of the virus from animal to a person, with a very high probability, happened only once. It occurred, as far as the speed of mutations allows us to judge, in late November - early December 2019.

According to reports, it can already be said that the speed of the evolution of SARS-COV-2 is quite high, which is typical for RNA viruses : on average, about one year in the genome in the genome in the year changes about one ( more precisely 0.8 × 10⁻³ replacements/site/year). This means that it will be quite difficult to develop a universal effective vaccine.

Studies of the differences between the new human coronavirus and coronaviruses of bats discovered at least two interesting facts that could explain how the virus managed to change the owner and become so contagious. It turned out that the s-protein, which forms spikes on the surface of the virus (thanks to them, the viruses received the “crown” in their name), in SARS-COV-2 has an additional website to cut the spike with one of the human enzymes. Neither SARS nor the nearest coronavirus bats have such a site. In addition, scientists managed to reconstruct the atomic structure of the S-White using cryoelectronic microscopy, and then, using modeling, establish that its affinity to the human target is much higher than that of the pathogen/SARS (“atypical pneumonia”). The stronger the virus binds to the target, and the easier then the s-protein cuts, the more likely, infection occurs. Such a double change in the viral “spike” was probably an important stage or even a condition for the transition of SARS-COV-2 from bat to a person.

A little details

The cutting of the spike is the necessary stage for the penetration of coronaviruses into the cage: first they attach to its surface behind the protein-target (in the case of both the new virus and the causative agent of atypical pneumonia, this is the ACE2 protein-it is found on the surface of the epithelium of the lungs and intestines), then the cell captures viral particles, forming membranes bubbles, forming membranes, Endosomes. However, in order to complete the process of infection - to get out of the bubble directly into the cytosol, you need to drain the viral membrane with the membrane of the cell. A separate S-protein domain is responsible for this, but it begins to work only after the S-White is cut with cell protease and, thus, is “activated”.

Different coronaviruses use different proteases of their owners, and the contagence and specificity of infection depend on this choice. The new coronavirus contains the site of cutting of the cell prosthesis Furina , which is present in a large number of human tissues. This does not mean that scientists reliably know that this enzyme really works in the process of infection - perhaps the same site is recognized by another protease. For example, there may be a TMPRSSS2V protease, the inhibitors of which, it turns out, can suppress the infection.

Disease

Three features of coronavirus infection were the subject of the most close research by scientists over the past month: the ease with which the disease is transmitted from person to person, the proportion of severe and lethal cases from all cases of infection and the possibility of asymptomatic transmission.

A conservative assessment of the indicator Rₒ (he indicates how many people infected on average one infected in a population, which does not have immunity to the disease) remained about the same as it was : about 2-3 people. One of the latest works on this topic suggests that the true assessment can be slightly higher (3.28), which was considered until some time (1.95), however, it is very difficult to get the exact number now, and in any case it will not be more than 1. That is, the epidemic itself will not stop, at least until a significant part of the population is vaccinated.

However, it should be borne in mind that Rₒ is an average indicator. As the case of the Diamond Princess liner shows or the flashes of incidence in South Korea, in some cases, “super-pronounces” may occur, for which Rₒ will be extremely high (with close contacts, up to 35% of people are infected). Secondly, this indicator depends not only on the properties of the virus itself (that is, stability in the external environment, the type of transmission, and so on), but also on the effectiveness of the deterrence measures that doctors take. And also from the structure of the population - the latest models show that in countries with a high share of older people, for example in Europe, Rₒ can be significantly higher than the average in the world.

Over the past month, the first reliable information about the mortality of infection appeared. Until now, it was considered a simple division of the number of deadly by the number of confirmed cases, which, as the Medusa already wrote , in the case of the developing epidemic, can give both overpriced and low significance. Preliminary data obtained by researchers at the London Imperial College based on modeling indicate that the proportion of deaths from all the ill -willed can be about 1% - this is significantly higher than the usual seasonal flu (~ 0.1%), but significantly less than the torso/SARS (“atypical pneumonia”) (9%). It should be remembered that this is preliminary data based on a very small number of deaths outside of China, and they can significantly change now that the disease is approaching the threshold of the pandemic. In addition, this is an average value, and for different groups of patients it can change greatly: in men, people over 60 and patients with concomitant diseases, the share of lethal cases may differ at times in the direction of increase.

Finally, clarity also appeared about the possibility of asymptomatic transmission of the virus. The first message about this, which concerned the case of the transmission of the disease in Germany from a woman who arrived from China, was not conscientiously verified - the carrier actually had symptoms. However, in recent weeks, the certificate of asymptomatic transmission of the disease has been confirmed in at least two cases in China. In one of them, a girl who came from Ujan to relatives to another city, five people infected. At the same time, she had no symptoms. She could not find signs of the disease even with the help of a tomographic study. However, the laboratory test showed the presence of a virus. In a similar situation was a family where only a 35-year-old man fell ill, and his wife and child did not demonstrate any signs of the disease, although the test results were infected.

The existence of a large number of incredible cases of infection is confirmed not only by individual diseases of the disease, but also by the results of mathematical modeling of the spread of infection. According to the latest calculations based on the data of the global air traffic, about ⅔ of all cases of infection imported from China, they remained non -cojected , despite the presence of checks at the airports.

Difficulties with detection are only aggravated by the fact that Chinese doctors several times changed the rules by which diseases are recorded. Including at some point they stopped taking into account the asymptomatic infections, which caused sharp criticism from scientists from other countries.

Treatment

For a disease, known for less than three months, there can be no medication with proven effectiveness. Conducting clinical research takes time: from several months to a year or two for each of the three phases of the study. This, however, does not mean that doctors are not trying to use what is already in their arsenal for treatment. In application to the Covid-19, two main strategies are most widely discussed: the creation of a vaccine and the use of antiviral agents-already past clinical trials, but in diseases caused by other pathogens.

As for vaccines, at least Chinese doctors and two American companies have already announced work on them: Moderna and Novavax. The first is engaged in the creation of drugs based on RNA - instead of inactivated viruses or their proteins, it uses a specially stabilized nucleic acid. This is a new approach, the effectiveness of which the company has not yet demonstrated not only on coronavirus infection, but also on other diseases. NOVAVAX is going to use a more traditional approach using recombinant viral proteins in the vaccine.

In any case, the development and testing of vaccines will take many months, and during this time the situation with the Covid-19 epidemic may radically change. This is how many scientists think, including the head of one of the US food control and medicine control department (FDA) Peter Marx. In a conversation with journalists of the relevant publication, he admitted that, according to the agency, the appearance of such a vaccine is extremely unlikely and no vaccine “will prevent a pandemia”.

Another strategy can be more realistic - the use of already known and tested antiviral drugs. At the moment, scientists are considering the potential effectiveness of many such substances . Here you can look at the overall spectrum of all known antiviral agents, and here to find out which of them are already included in clinical trials. Most often, the most promising of them are called the following:

• Remesivir is an antiviral agent of wide action, a synthetic analogue of one of the “letters” in the composition of nucleic acids developed by Gilead. It has already been tested on the Ebola virus and showed good results in the case of some other coronaviruses and in individual cells infected with a new virus. It is believed that the abodezivir inhibits the SARS-COV-2 replication due to the fact that it makes the RNA polymerase make many errors. In the informal guide of WHO, created on the basis of consultations with specialists, it is called the most promising of antiviral drugs. It was also used in the treatment of the first case of the disease in the United States. However, the authors emphasize that a single case of recovery does not say anything about the effectiveness of the medicine.
• Favipiravir is another inhibitor of viral RNA polymerase. It is used in one of the clinical studies in China, but laboratory tests did not show it sufficient efficiency against SARS-COV-2.
• Ritonavir and Lopinavir - Protease inhibitors developed to combat HIV. Since part of the coronavirus proteins is initially synthesized as a single polypeptide chain, for functioning it requires cutting with proteases - and these substances just suppress the work of such enzymes. The drugs were studied on the pathogens of SARS and Mers and showed some positive results. They are already used in several clinical studies for the treatment of COVID-19.
• As well as many other substances , including those found using machine learning .

The first results of the starting clinical studies can be expected in May 2020.

That is still unknown

As before, the exact mechanism of transmission of the virus and the share of asymptomatic cases, the rate of spread of infection and possible treatment options remain poorly known. The assessments of mortality are still very approximate.

In addition, due to the fact that the spread of the epidemic has passed into the new phase, measures such as temporary closure of schools are considered. However, it is poorly known how the Covid-19 transfer children. Apparently, the course of the disease occurs in a less pronounced form, but it is not clear how this affects their ability to spread the infection.

Where to follow the news

All there

• Special page of the World Health Organization (WHO). Here they publish daily reports on the development of the situation. Since the number of infected ones is constantly changing, specific numbers in the reports can be somewhat outdated compared to other sources.
• The centers for the control and prevention of US diseases (CDC) also started a page dedicated to the epidemic in the country.
• The interactive card that is supported by the GISAID international research project. Data is collected from several sources: WHO messages, CDC and the National Health Commission of China.
• The aggregator, collecting the latest information about the sick, which is published by the Chinese authorities and local media.
• Page about coronavirus on the Rospotrebnadzor website
• Several resources for doctors and specialists: one , two , three , four .

Alexander Ershov