"This is not even a pre-pandemic situation"

When will the coronavirus epidemic end?

Vadim Bondar, "BUSINESS Online"

"There are no specific drugs against the Chinese coronavirus yet. Doctors use approaches to treating people with pneumonia in the form of complications after the flu," says virologist, member of the working group on vaccines of the International Federation of Pharmaceutical Manufacturers and Associations IFPMA Yuri Vasiliev.

He told BUSINESS Online about the time in which the Russia will create a vaccine against the virus, why everything is not easy with the way of its transmission, who decides on quarantine and how scientists in the United States and Europe almost published instructions for creating a new bird flu.

"It looks like ARI, and it's not a fact that it's of viral origin"

– Yuri Mikhailovich, to begin with, how do the symptoms of coronavirus differ from the symptoms of influenza or acute respiratory infections? Can they be confused? For example, not the most experienced doctor can make a wrong diagnosis?

– To simplify, they are no different. It looks like an acute respiratory infection, and it is not a fact that it is of viral origin. What we call ARI. If in dynamics, then one of the manifestations is pneumonia. Accordingly, all the recommendations – both the WHO and the Ministry of Health of the Russian Federation – boil down to the fact that it is necessary to take appropriate samples and send them for analysis. This is a molecular virological diagnosis, in particular a polymerase chain reaction, which allows us to confirm very quickly, highly sensitively, and specifically that this is a Chinese coronavirus. Or, if it is the flu, it will be possible to confirm with the help of appropriate kits that it is him, taking into account serotypes, and so on.

– As a person connected with this problem, tell me what about the vaccine, when will it really appear?

– There is a certain nuance here. There are approaches, in particular peptide vaccines, where the vaccine itself, the antigen (active ingredient), can be developed within days. But, unfortunately, such vaccines are very expensive and, in terms of their effectiveness, in light of the features that have not yet been resolved, are clearly insufficient. The working option, which, by the way, does not imply the presence of the virus itself, which can be started with a genetic sequence (which many institutes around the world, including in our country, are actively engaged in), is the so–called vaccines based on recombinant proteins. They are made by analogy with the vaccines being developed against the Middle East coronavirus (MERS), as well as SARS 2002-2004 (SARS). Since the virus is new, of course, the vaccines that will turn out may have a suboptimal ratio of efficacy and safety. Only research will show this. But in general, I would say one and a half to two months, taking into account the fact that they started working already about two weeks ago, it will take to get the first milligrams of the active substance - recombinant protein. But it will not be a vaccine yet, because each country has its own characteristics. In general, in order for the drug to become a full-fledged vaccine, it is necessary to test it on animals by conducting so-called preclinical studies. The first results of these tests will appear in a few months. In particular, in the Russian Federation, certain safety indicators according to an officially published methodology, which everyone follows, takes up to six months. And then, when there is already a candidate vaccine with data on efficacy and safety in animals, appropriate formal procedures are carried out, all this is done through the ethics committee and so on, and then everything goes to the stage of clinical trials with the participation of volunteers. This will also take some number of months. Therefore, the first doses are one and a half to two months, and the first vaccine registered in the Russian Federation, of course, may take a time interval of one year.

But there is experience, for example, in the USA, just for such situations – as a result, a drug that can be used will be obtained faster. What is this experience? They have a procedure when, in the case of a biological threat or some other threat, some stages are not carried out, and permission is given, in particular, to conduct clinical trials with an incomplete dossier for preclinical trials. At one time, in 2009, during the outbreak of swine flu, when the situation began to escalate in April, the first results of studies involving volunteers were published in July – August of the same year. Thus, it took only three to four months to assemble and test the experimental vaccine, and it became possible to switch to volunteers almost immediately. But this is America, it has its own procedures that allow you to do this.

– If there is no vaccine, what is the coronavirus being treated in China and what will be treated in Russia, if the disease begins to spread actively in our country?

– Unfortunately, there are no specific drugs against the Chinese coronavirus with proven safety and effectiveness yet. And there are corresponding entries about this in the temporary recommendations of the Ministry of Health of the Russian Federation on how to act in the case of this infection, which have already been issued, in my opinion, by the second edition. There are even the first scientific publications about modeling, about laboratory data on which drugs from the already available, either from experimental or already registered, may have activity against coronavirus. According to this strategy, it is possible that drugs will appear in the near future, in respect of which specific activity against coronavirus will be shown. I emphasize: it is possible. Then it will be possible to proceed to preclinical and clinical studies. But even with this outcome, the time horizons will be at the level of months.

– And what are the patients being treated with now? After all, people are hospitalized, something is done and people recover? We have two Chinese, according to official sources, cured.

– What we have just discussed is called etiotropic drugs in medicine, that is, those that affect the causes of the disease (in this case, the virus). There is a pathogenetic direction of therapy that affects the mechanisms, how the infection, the pathological process develops. And there are symptomatic approaches – to alleviate, so to speak, the manifestations of the disease. The latter are used. They are also included in the temporary recommendations, including the Ministry of Health of the Russian Federation. If you give examples, then breathing difficulties (certain functional indicators) – this is the use of artificial lung ventilation. Some violations of the water, electrolyte balance – the corresponding intravenous infusions. Conditionally, supportive therapy. This does not mean that no one knows what to do. Doctors in the field who have experience in the treatment of pneumonia, regardless of the cause of this pneumonia as a clinical condition, apply the approaches that they use in the treatment of people who have, for example, pneumonia in the form of complications after the flu.

– What precautions should Russian citizens take? Are there any regional differences?

– There are no regional differences. Here, all approaches to non-specific prevention are, in general, the same. This is, first of all, hand washing. Respiratory hygiene, if a person sneezes, coughs; use disposable napkins, handkerchiefs, which are then immediately thrown away, and hands are washed. And with regard to the Chinese coronavirus, since the natural source of its origin is not excluded, interaction with domestic and wild animals should be minimized as much as possible. In the case of eating animal products – heat treatment. It is necessary to refrain from prolonged communication with people with obvious signs of respiratory diseases. These are the recommendations that we always issue at the peak of the epidemic season, for example, influenza.

– A separate question is how to protect children, because they literally pull everything into their mouths, actively contact each other and with different adults?

– Just the other day I came across an article on epidemiological data of the first thousand cases of diseases in China. So, there the authors write that the median age is at the level of 50 plus. By the way, it is also very interesting why this is so. That is, the data currently available do not reveal any additional risk factors. For example, when there was an outbreak of the Zika virus, which took place in South America a few years ago, the fact of the greatest severity of the disease in pregnant women, especially with regard to the health of the child, almost immediately surfaced there. Here we do not see any such factors, and here, as the latest rechecked data indicate, it is rather the average age and older. As a result, the risks for children are somewhat lower. And from a scientific point of view, it's very interesting why this is so. We will sort it out, communicate with colleagues. I think we will get answers to all these questions in a few months.

"The number of really sick and infected may be underestimated"

– Who decides whether to quarantine a person, family or other group of people or not? What is quarantine, how long does it last?

– There is a consensus opinion on the duration: the incubation period is from 2 to 10 days. What is applied in practice, including in our country, in the Russian Federation, to evacuated citizens and in the case of a cruise liner off the coast of Japan, is a two–week quarantine period.

Then the specific situation on the spot and the degree of risk minimization matter. A similar situation can be considered on the example of a cruise ship in Japan. There, the authorities of the country make the appropriate decision, since the ship is in their territorial waters, and I understand that the shipowner company is also Japanese. There it was decided to quarantine all participants for two weeks. Further, if someone gets sick, the quarantine is extended only for those persons who have been in direct contact with the sick person or the sick. To minimize the risk as much as possible, if possible, as was done with our citizens evacuated from China and located near Tyumen, where, as far as we have seen, read, looked at photos, they took this issue very seriously.

Usually, in such situations, what do they do? This is a screening for fever, a questionnaire, and the medical professional who analyzes it all already makes a decision about further actions – to send a person for diagnosis or somewhere else. Express diagnostics is fast enough, and thanks to it you can get an exhaustive answer to the question whether a person has a coronavirus infection or not. Further, if there is an infection in someone who arrived, say, by plane, then people are either interviewed again, examined, or a decision is made and they are quarantined. In general, it all depends on the specific situation at a particular point. China, for example, has taken this issue very seriously in order to minimize the risk of infection by using all available forces and means. Other countries, at least, are not doing so yet.

– The London School of Hygiene and Tropical Medicine has made a forecast: the epidemic of coronavirus infection will reach its peak in the second half of February. The forecast was made based on the method of mathematical modeling (combined information about the spread of the coronavirus that caused the SARS epidemic in 2002-2003, and data on the current situation). According to scientists, about 500 thousand more people may get sick. Do you agree with such calculations?

– The data on the dynamics that is available (there are, however, not very many of them) indicate a certain slowdown, reaching a plateau or at the peak of the spread of infection. Separately, I would like to note that the actual epidemic process may differ from what we see. In particular, not all people, even after the appearance of the corresponding symptoms, seek qualified medical care. Therefore, the number of really sick and infected people may be underestimated. But, on the other hand, due to this fact and the fact that all cases of severe infection with suspected pneumonia are carefully analyzed, the number of deaths, if not overstated, then let's say, is at the highest possible level. Taking all this into account, the forecast that the peak of morbidity will be in February – March, then it will decline, is quite realistic. God grant that it will be so.

As for the total number of cases, it seems to me that it looks unnecessarily pessimistic in this forecast. Where, with the current dynamics, half a million will come from at the end of February, it's hard for me to say. I think that in March the situation will begin to come to naught, and in April we, as virologists, will be able to calmly understand the situation and prepare for possible new outbreaks, which will certainly occur in the near future.

– Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, said in an interview with The New York Times that the virus is very, very contagious. "It's almost certainly going to be a pandemic." Do you agree with this assessment? What will happen if WHO declares a global pandemic? How will our epidemiological and medical authorities, the authorities in general, react?

– If the situation was close to the pre-pandemic, then over these two months, and maybe more (there is an opinion of scientists that the first cases of coronavirus were not even in December, but in November), we would have a completely different story and picture. There would be a meeting of the World Health Organization with completely different solutions.

I would especially like to emphasize that the term "pandemic" in the classification of those definitions that appear in the WHO is currently developed only for influenza viruses, because they still have the highest pandemic potential. There is no longer a single infectious agent for which the WHO currently uses the term "pandemic". It was for influenza that a six-stage system of pre-pandemic and pandemic danger levels was developed at the time.

The 2009 swine flu outbreak, which many experts do not consider a pandemic, but which the WHO still declared a pandemic and which stopped at the fifth level out of six, had a completely different dynamic. There were days when dozens, if not hundreds of thousands, of cases of infection around the world were confirmed and uploaded to the WHO system. Then there were thousands, and sometimes more, who died every day. It really was a pre-pandemic situation. The dynamics with coronavirus are a little different now.

"We do not know the confirmed ways of transmission of this virus"

– Our doctors have arrived in China, but the doctors there do not give them a strain of the virus. Why?

– In a crisis situation, it is best to operate only with official sources, and such information on them is very limited. I can only say that in any case, the virus can be obtained through WHO, as it was in previous cases, in particular during the outbreak of swine flu in 2009. Then WHO, through its system, took on this task. Thus, getting a virus is a solvable issue.

In general, it is not very clear how the situation will develop. Most likely, it will slowly come to naught. In our country, coronaviruses, according to the standards of technical documentation, belong to the pathogenic biological agent of the second group. These are dangerous infections, and you need to immediately understand that there must be appropriate logistics for their transmission, and you should take into account which organization all this will come to in the Russian Federation. To summarize, our Vector Institute, located near Novosibirsk, was included in the promptly created group of centers cooperating with WHO on coronavirus. That is, there are by and large no significant obstacles to the transmission of the virus, but some technical issues are possible.

– To the question of logistics. A lot of very different products manufactured in China, including food, are still coming to our country. In the Far East, according to a temporary scheme, cargo checkpoints were even opened for vegetables and fruits from The Celestial Empire. What is the probability of getting infected through these products and goods? Fruits and vegetables, after all, can have the smallest damage, into which many dangerous microorganisms fall. In this case, is it not scary?

– Again, so far we do not know the confirmed ways of transmission of this virus. But what I want to say from a scientifically sound standpoint: the first signs of infection were in China in the first decade of December last year. Two full months have already passed, and the dynamics of the spread of the disease in China, and mainly in the province where the city of Wuhan is located, as well as the small number of cases that occur around the world, suggests that if there were any suspicions that there is such a risk - and Chinese goods they are coming not only to us, but also to almost all countries of the world, including a huge mass of them in the USA – then we would already know about it. This would be included in WHO circulars, in the recommendations of our Ministry of Health, and so on. To date, it is known that the Chinese coronavirus persists in the environment for up to 9 days. For viruses, this is not so little. But even with the hypothetical consideration of contamination logistics, customs clearance usually take more. On the other hand, the risk that a person infected with this virus will transmit it to a manufactured product at the current level of automation is minimal. It's just hard to imagine how he can get there and stay there. This is unlikely. And now it is at least premature to say that there are any risks of this kind.

Here you can also give an example of a cruise ship off the coast of Japan. If the virus was so actively transmitted by airborne droplets or some other way, then during the period that the liner is there in almost complete isolation, there would be significantly more people infected with coronavirus than now. This story once again emphasizes that, yes, in general, a difficult situation, yes, the virus poses a threat, but this is not even a pre-pandemic situation. This is an outbreak of a new virus mainly on the scale of one region of one, albeit a large country.

I would like to emphasize that WHO has declared the situation with the Chinese coronavirus relevant for international health because only after such an official announcement can international organizations, starting with WHO and ending with the UN, begin to provide the country with the necessary assistance and participate in the situation. This is implied by the relevant programs of the mentioned international organizations. Currently, such assistance to the People's Republic of China through various international organizations and sponsors is being provided quite actively. It is already planned to allocate about $ 675 million from various donors for three months for operational measures to combat coronavirus. All this would have been impossible if WHO had not declared the situation relevant for international health.

– There was already an incident in St. Petersburg with the Chinese who tried to enter the music salon without a mask. People began to fear contacts with Asians, Chinese tourists complain that the locals shy away from them. Does all this have any grounds? Should we be afraid of people who may be from Southeast Asia, and not approach them?

– Even at the very beginning of the development of the situation, namely during our wonderful New Year holidays, when the media had not yet picked up the whole story, one of the first WHO circulars described the situation with a confirmed coronavirus disease outside the PRC. There is a very interesting situation there. An elderly woman was flying on a plane from Wuhan to Bangkok, Thailand. There's a four-hour journey. She was flying with an organized tour group. It is clear that they were all in very close contact with each other, it was in this tourist group. Upon arrival, the passenger was found to have an elevated temperature. Accordingly, events were held, and the entire board was subjected to a thorough diagnosis. As a result, it was determined that no coronavirus was detected in any passenger who flew for four hours in a confined space with a patient. The fact that one of the passengers was diagnosed with another respiratory virus speaks in favor of the fact that the diagnosis was carried out qualitatively. This is another example of the fact that coronavirus is ineffectively transmitted from person to person. Yes, the thousands of cases we see today are large numbers. I agree. Unfortunately, there are fatal outcomes. But taking into account these facts, taking into account the fact that the situation is already in its third month of development, it all looks not as alarmist as it might seem, relying on some unprofessional publications in the information space. For comparison: a few weeks ago, the American CDC published preliminary results of the flu epidemic season, the data speak for themselves: 15 million people who were ill in The United States of America and about 8 thousand deaths. I think the nuances are clear.

"There is no information on reliable identification of the original source. So far, everything is at the level of hypotheses and speculation"

– Yuri Mikhailovich, China seems to be a fairly advanced country in medical terms – why did such sensational diseases as SARS in 2002-2003, avian flu, swine flu, and now coronavirus appear there?

– In fact, this is not quite true. It just so happened that China was not the most hyped in this regard for specialists, or something. Here are some examples. So, last year, according to the reports that we receive through the World Health Organization, the second of the three coronaviruses was the Middle East. These are countries such as Qatar, Saudi Arabia, and other states in the region where the virus is released and this story continues. Let me remind you that the Ebola outbreak in West Africa was mainly in the Democratic Republic of the Congo. As you can see, this is not China either. Other infections that the world community has also been paying attention to over the past year are outbreaks of yellow fever, outbreaks of Dengue fever. We all know that measles, despite the availability of effective vaccines, due to the low level of vaccination, anti-vaccination movements, is beginning to recapture the positions that humanity has managed to achieve in the fight against this infectious disease. Therefore, I do not quite agree with the postulate that all infectious diseases from China. Such outbreaks occur all over the world.

In terms of scientific advancement, yes, indeed, I can say that the People's Republic of China invests a lot. In recent years, the number of publications in respected peer-reviewed journals has been growing and, of course, their level of development is quite high. There are also opportunities to diagnose viral diseases, including new ones. It was the Chinese who published the genome-wide sequence of the new coronavirus on January 12, which were then also published in other countries.

– Some conspiracy theorists claim that this is all for a reason. For example, as soon as China began to actively develop its own poultry farming and intensively reduce purchases of poultry meat in the United States, avian flu began there. To justify their theories, conspiracy theorists say that Cambodia, Haiti, India and a number of other countries have terrible poverty and unsanitary conditions. There they eat much bigger rubbish in the form of insects, snakes, marine life, which are not eaten by other peoples, even poor Chinese, and no epidemics are born there. And in China, which is getting richer and gaining strength, they are literally one by one. Why?

– In fact, infections occur there and in other places. I have already said a few words about Ebola, which is transmitted almost exclusively through direct contact of biological fluids. This means that their national characteristics contribute to the fact that it is not yet possible to completely extinguish this outbreak. Again, what have we seen in other countries in recent years? It's polio. There is a global polio eradication program under the auspices of WHO, which is now in its final phase and there are several hotbeds of wild polio virus circulation, these are some regions of Central Africa, and the hottest region in this regard is the border of Afghanistan and Pakistan. There, the quality and standard of living are appropriate. Plus, security conditions prevent UN missions from working calmly and promptly, detecting cases of the disease and conducting vaccination campaigns. Therefore, the source of viruses dangerous to the whole world is not only China, but also other regions around the world. I would even like to emphasize that not only countries with low and average living standards. Because of the anti-vaccination movements, there is a big problem characteristic of the most developed countries, Europe, the USA. Unfortunately, in our country such a problem also manifests itself. The low level of vaccination against diseases such as measles leads to a high increase in the number of cases in developed countries. Viruses and other dangerous infections know no borders, and outbreaks can occur almost anywhere in the world, as well as spread in any region.

As for China and the market of live animals and seafood, from which the current coronavirus epidemic allegedly originated, then, unfortunately (despite the first publications in peer-reviewed scientific journals, where specific scientists report specific facts that reviewers checked), we do not have information on reliable identification of the primary source from where exactly this virus appeared. So far, this is all at the level of hypotheses and speculation. It is possible that all the information related to this market and specific animals, bats, and so on, that the virus has mutated somewhere, crossed the interspecific barrier and got to a person, will not be confirmed. This is the most likely hypothesis, but it has not yet been confirmed.

– And why are interspecific transitions of diseases from animals to humans becoming more frequent? Avian flu, swine flu, and now, presumably, coronavirus? Will this happen more and more often?

– Yes, you have correctly noted and highlighted the problem. There are two factors here. Firstly, the objective situation presented in the form of globalization, intensification of all processes, urbanization, and so on. People live more massively and cohesively in cities. There is an intensification of animal husbandry, poultry farming. Contacts of pigs, cows, birds with people on farms are accelerating and the transition of viruses from animals to humans is possible. Secondly, perhaps even more important, is the development of science and technology, in particular related to the possibilities of molecular virological diagnostics. That is, today it is possible to very sensitively, very specifically identify, in minimal quantities of samples, quite reliably what kind of virus it is. If this is some kind of new one, as was the case with the Chinese coronavirus, then you can quickly make a genome-wide sequence, decipher it and understand what kind of organism it is, and how it relates to others. Therefore, yes, the dynamics that we have observed in recent years is possible – avian flu, swine flu, coronaviruses – this is from what can be heard. Now we all know that. 50-60 years ago, before the era of molecular diagnostics, this outbreak would have been designated as atypical pneumonia of an unexplained nature, and they would not have been able to decipher that it was a coronavirus. It would be considered simply that it was some kind of bacterium. Unfortunately, this trend is likely to continue, and in the coming years we will increasingly encounter outbreaks that we can now characterize very quickly and accurately.

– It turns out that although people lived side by side with animals before, but "interspecific diseases" were simply not diagnosed?

– Yes, on the one hand, there were no opportunities for diagnosis. Plus, the dynamics of life, the mobility of citizens was not as high as it is now, when in 20 hours you can fly to almost anywhere in the world. On the other hand, the evolutionary process is still going on and accumulating. A few years ago, there were not yet so many mutations and adaptations of animal coronaviruses that one of them could pass to humans and began to infect them. A curious work on the analysis of the Chinese coronavirus with other coronaviruses came out here the other day, and it was revealed that somewhere 70 percent of the Chinese coronavirus is identical to the SARS virus of 2002-2003, and somewhere about 30 percent, I don't remember exactly now, is identical to the Middle East coronavirus. They calculated that about 380 mutations had to be accumulated by the Chinese coronavirus in order to become the virus it became. Accordingly, it takes biological time.

– In any case, so far most of the data suggests that people of the Mongoloid race mainly get sick and suffer the disease in the most severe form. This may indicate an increased susceptibility of representatives of this race to a certain strain. After all, the coronavirus can be artificially removed or become a side result of human activity, some kind of hybrid of human activity and a natural factor?

– Regarding the fact that this virus was artificially created: again, we have a genome-wide sequence of this Chinese virus, which was isolated from patients in different countries. There are already several dozen sequences, they are in various open databases, very intensively analyzed, including for possible sources of origin for the development of drugs for therapy, diagnostics, vaccine creation, and so on. Therefore, I will say this: if there were any concerns that there are some mutations that fall out of the natural biological process, and there are appropriate bioinformatics specialists in the world to identify and identify them, then people would definitely pay attention to this. It is worth giving such an example here. Five or seven years ago, even before the publication of the articles, two teams of scientists in the USA and Europe, in Holland, as far as I remember, simultaneously identified point mutations that could allow the avian influenza virus to be transmitted more effectively from person to person. That's where the animal model was used. And even before the publication, those reviewers who watched it, let's say, raised the alarm about the possible double use of these results, and so on. The situation has been made public. As a result, the articles were published, but with the exception of technical details that would allow it all to be reproduced. Why this example? To the fact that the international scientific community is now open and transparent. All these sequences are there. If there were any concerns, I'm sure we would have known about it by now. After January 12, literally in a few days, someone would have found some analogies, links to articles cited how something like this could be. This is about the artificial origin of this virus.

I can also say that it is very difficult, even hypothetically, to create mechanisms, approaches that could be used to construct and modify a virus so that it has a selective capability against people. Then there are many more moments. In particular, it should be understood that the PRC is a multinational country in which a lot of ethnic groups and nationalities live. And even taking into account this factor, the hypothesis that the virus acts selectively against a certain type of people does not stand up to criticism.

On the other hand, if this is selective for residents of Southeast Asia in a broad sense, then we see fresh data, from which it follows that the absolute majority of cases are in China and a relatively small number outside the PRC, including in countries such as Hong Kong, where a lot of Chinese live. In general, it is almost impossible for someone to artificially create this situation. Moreover, why exactly did this outbreak occur in the Wuhan region? Now the scientific community is increasingly discussing the topic that the virus is not as effectively transmitted by airborne droplets as it is by contact, which explains the dynamics of the spread around the world that we are observing. That is, we see tens of thousands of cases in China and several hundred confirmed cases around the world. Either airborne transmission is very inefficient, or other transmission methods are connected.

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