"The isolation regime may last 12-18 months": the medical director of the pharmaceutical company - on the treatment of COVID-19 and vaccines

- Let's talk about what is being treated or trying to treat coronavirus around the world. Here is a famous tweet from Donald Trump, the best therapist on planet Earth, that they found a cure: hydroxychloroquine, azithromycin. Hydroxychloroquine is a known cure for malaria 70 years ago. Azithromycin (sumamed) is a wonderful antibiotic, invented by our Yugoslav friends back in 1980, in the Pliva Zagreb laboratory. Is it really effective against coronavirus?

- I can note a number of factors that influenced this trend. That is, why Trump reproduced this information, why Ilon Musk originally tweeted ...

- Also, of course, the main therapist on the planet, the main virologist ...

- The main innovator. All this was based on a small publication, which was posted in an accessible public publication. She summarized a small pilot study that was conducted in France. 26 patients with coronavirus received hydroxychloroquine. And the result of this study was evaluated: the effect of taking this drug on the timing when the patient stops secreting the virus. That is, the dates when it can hypothetically cease to be considered a carrier and distributor. This study showed that by the sixth day, most of these patients, 57% who received only hydroxychloroquine, stopped giving it away.

- Without sumamed.

- Without sumamed. With the addition of sumamed, the number of patients who stopped giving out reached 80 percent. This is a very good result, in fact, and it inspires certain optimism, from the point of view of the further use of this drug, but not in treatment.

- And what?

- I will make a reservation, why not in treatment. This study has a definite drawback - it did not evaluate the clinical outcome. That is, what happened to patients who took this drug. That is, they recovered, did not recover, from what cohort the patients were, how much they went to intensive care ...

- Understood nothing. So people got this hydroxychloroquine.

- Yes.

- Other people received hydroxychloroquine with sumamed.

- And the third placebo.

- And the third received a placebo. And they all recovered the same way?

- It was a very short study. It evaluated the results in just a few days. The sampling of patients was minimal, of the 56 planned, most were eliminated. And, actually, until the end of the study, until the moment when it was possible to take these results and somehow interpret them, a relatively small number of patients reached. That is, all these results have lost their statistical significance.

- That is, we do not really understand if hydroxychloroquine is so good, sumamed, right?

- That's right. In reality, we cannot now reliably and unequivocally state that yes, this is it.

- But at the same time, I saw Belgian recommendations yesterday: yes, give everyone hydroxychloroquine and in six days you will all be healthy.

- Here we turn to a situation where in the instruments of doctors, in principle, there is no treatment for certain diseases. And when, in general, any medicine that shows at least signals or trends that it can be effective in severe patients, it is used by doctors. Provided that we know reliably its security profile.

- Here, this is the most important question. How do doctors decide which medicine to use? Why hydroxychloroquine? There was some cure for malaria. Malaria is generally caused by some kind of microorganism that enters the human body. Why did people suddenly come up with the idea that it could help against the virus?

- The process is long, capital-intensive, and it usually does not happen all of a sudden. Chinese scientists drove a large number of molecules through a specific panel of coronavirus infected cells. Known molecules for the purpose of repositioning them. The discovery of new properties in them, which in the future will allow them to be used according to new indications. This is a universal tactic for a very large number of companies in the Western world - re-positioning drugs in order to open a new market niche for this drug.

- So, for example, the first cure for HIV infection was discovered - zidovudine, which was invented in 1968 as a cure for cancer .

- That's right. And this very run showed that it was hydroxychloroquine, in their study it was chloroquine, which significantly reduced the rate ...

- They differ? Are chloroquine and hydroxychloroquine different?

- Slightly. There is a question in metabolism. The active component is the same. As a result ... but they showed that hydroxychloroquine is several times more effective in terms of ...

- Than just chloroquine.

- Yes, in suppressing virus replication than just chloroquine. They built a model that allowed them to assume that if you use this drug in a certain dosage regimen, it will be three to four times more effective than taking chloroquine in patients infected with coronavirus. Based on these data, they launched two clinical trials. At least two that appear in official sources that are now coming. These are hydroxychloroquine perse and hydroxychloroquine in combination with another drug.

“Perse - that means on its own.”

- By itself, monotherapy, yes. And the second is a combination with caletra, lopinavir-ritonavir.

- Does coronavirus look like HIV, and are HIV drugs, in particular, a protease inhibitor, really effective for treating coronavirus infection?

- Coronavirus is an RNA-containing virus, and it is included in a large family of viruses that contain exactly RNA - ribonucleic acid, a chain as a carrier of genetic information. This also includes hepatitis A, all the rare African diseases, this is Ebola virus, Nile fever, and so on. HIV conditionally refers to RNA-containing viruses, because for its reproduction it requires some stage when its DNA is transformed. He requires an intermediary. That is, he must synthesize DNA, and RNA will be read from it again. Reverse polymerase ... revertase. Therefore, it does not apply in its pure form to RNA-containing viruses.

- In general, we know quite a lot about diseases caused by viruses of this kind, acute respiratory viral infections. What is the difficulty? Why is monotherapy not used? Why is it necessary to mix all these drugs with each other, torment people with these jars?

- It sounds dramatic. I will explain why. The unique ability of RNA viruses is that they mutate very quickly. There is not a single virus replication cycle that reproduces the same virus. Each cycle is a mutation, each cycle is a mutation. And, in fact, during the generation of the nth number of viral particles in the cell, there is not a single similar particle. When the Chinese transmitted the same 30-60 strains isolated during the epidemic, it already had 149 mutations.

- 60 strains. 149 mutations.

- Yes.

- For two confirmed months of the Chinese epidemic.

- That's right. There was one strain, but there were subspecies.

- For the entire HIV epidemic, for comparison, this is 40 years of almost confirmed - 72, in my opinion, strain.

- Yes. Coronavirus has a great many of them. Several hundred circulate in the animal population, the so-called wild virus. And about a dozen, from ten to 30-40, are among the people. Coronavirus is a common causative agent of acute respiratory infection. In fact, seasonal infections, spring-autumn, 15% are coronavirus. But it proceeds quite easily. Runny nose, cough - and went.

- As usual.

- Yes.

- Like 80% of the course that is with this coronavirus.

- That's right. But the coronavirus has the ability to exchange its genetic material between particles. This is the so-called recombination. Moreover, it can exchange not only between coronaviruses of a human strain, it can exchange them with wild species of animals, what happened, in general, in China, is the very coronavirus that went further from the bat and caused everything, what caused. Here is a unique property of coronaviruses.

“Can we say that now there is, in fact, no effective cure for coronavirus?”

- We can say that today there is no drug with unequivocally proven effectiveness. All we have is fragmentary data, which are now received literally in the fields, from individual clinical centers, they simply aggregate this data and send signals: we did it, but we did it, and it seems to have worked for us. And so on. The problem with this data is that the patient pools are very small. They do not allow them to be uniformly aggregated and to conduct statistical analysis.

- Why did this happen in Italy?

- Definitely no explanation. We can only say that now, according to statistical reports, a more mature patient population is affected in Italy. This is a 50-60 plus. And these are patients whose initial prognosis is worse. 10% of them develop severe complications, even more, their mortality rate is 10%. The young population has a mortality rate of about 2-3%. The elderly - 10%. There are still gaps, risk groups. There are about 5-6%. It is this pool of elderly patients for no apparent reason that no one can explain; it is now concentrated in Italy. Therefore, such a high mortality rate. And, apparently, late anti-epidemiological measures were launched. Because literally an epidemic instantly swept the entire peninsula. There was not a single province that would not have been infected.

- At the same time, the main burden fell on the northern rich provinces, where just the elderly and very elderly people live in a concentrated manner.

- By the way, Italy and Spain belong to the category of countries where one of the highest life expectancies.

- Let's talk about the vaccine. In general, we understand the technology for producing vaccines for respiratory diseases. She has been known for a long time. It differs only in details, depending on what kind of disease it is. Why isn’t she?

- Vaccines for RNA-containing viruses are very difficult to develop. There are viruses more or less stable. For example, hepatitis A virus. There is a vaccine for them. There are viruses that are very unstable in terms of mutation frequency. As I talked about coronavirus, each new replication generates an already mutant virus particle. They are not similar to each other.

- That is, they are not copies. He does not redo himself.

“These are not absolute copies, yes.”

- That is, it enters a cell, it produces a large number of viral particles, this cell breaks down - and these are not exactly the same viruses that were before.

- That's right. Therefore, before you begin to develop a vaccine, you must identify some unique common parts of this virus, on the basis of which you can create some kind of vaccine. Usually these parts are few. And in order to calculate these parts, you need to analyze the nth number of hundreds of strains of this virus, including wild strains. Just the very materials that the Chinese transmitted, the information somewhere on 200+ wild strains and 30+ human, and now allowed to highlight ...

- The vaccine, what's wrong with the vaccine? When it is?

- The problem with coronavirus is that even when you create a vaccine strain, relatively speaking, it can still exchange its parts with a wild virus. And the vaccine that you created now, relatively speaking, in the fall or next January, will no longer be effective.

- And how then do we develop population immunity?

“We need to wait for the development of the vaccine.” Those same, relatively speaking, the isolation regime in all countries will last 12-18 months.

- That is, we all that you really want to say should sit under house arrest for a year?

“In the saddest scenario, yes.” That may be so.

- I do not believe in that.

- I did not believe in much before the start of this epidemic. I did not believe that there would be more than 100 thousand people infected, focusing on SARS-1, where there were only 8 thousand.

- That is, the task is not so as not to get sick, but the task of making sure that everything is at the same time, as now in Italy ...

- To not get sick at the same time.

- Yes.

- Sooner or later, almost everyone will get sick.

- Here. And so that everyone wouldn’t be in intensive care at the same time, they would not occupy all the corridors, all the toilets, the public spaces of these hospitals, so that everyone would not have to take these IVL devices from China or, God forbid, Ekmo, right?

- Already there are publications that some of our comrades buy mechanical ventilation for themselves, at home ...

- I think that they also hire, naturally, some junior medical personnel, of course.

- For this there should be a support team, not only a junior, but also a senior. Therefore, I do not know how much this ...

- Still need a resuscitator in the team. It’s necessary to immerse you in sedation.

- That's right. Plus maintenance therapy. Therefore, most likely, this is just a panic. Because the ventilator at home is unlikely to help for this particular owner of the ventilator. But this is so, marginal notes ... Lost the thought.

- The idea was very simple, about vaccination, about what we are waiting for ... On the one hand, you say that it is very difficult to make a vaccine, because the virus mutates so quickly. We’ll do it now from one of these two strains, probably from the aggressive one itself. And on the other hand, you say that we must wait for this vaccine, despite such a rapidly mutating virus. And I say: maybe we won’t wait and maybe we won’t observe this quarantine, but let’s say frankly: let the old people observe the quarantine, because they will be massed in these intensive care units. And young people will not be. This is a question of China.

- This simulation included such a scenario. And he estimates a 75% reduction in the burden on the healthcare system. As a result, it is isolation of risk groups and elderly patients. At the same time, a parallel scenario, namely, large-scale measures to limit movement, isolation, and so on, is more effective in terms of reducing the load on the general population. Because young people also get sick.

- And also difficult.

- According to Chinese statistics, 80% of patients fell into the “plug” from 25-30 to 60. Children practically do not get sick, there were less than 1%. There was an American article on the fair allocation of resources in conditions of shortage ... And there was a suggestion that vaccination should be done first of all for risk groups and the elderly. I doubt the appropriateness of this approach, because they are not carriers.

The carriers are those same 80% of the young, active.

- Well, that's good. Still, it is a matter of the fact that someone is a carrier, and someone will die. There are people who will suffer this disease, and will not even notice. Here, the granddaughter is 10 years old.

- 25%.

- Oh sure. But, you say, the children do not get sick. Children under two years old do not get sick. So, maybe, really, still the grandmother needs to be vaccinated, and not the child in this situation?

- Here comes the second moment. We are talking about unexplored products. Accordingly, we do not fully realize how safe they are for the same grandmother. All studies that are ongoing are clinical, they have an upper cut-off of either 50 or 60 years. You do not know how this product will behave in the elderly population. It hypothetically can increase mortality, as the product itself. And no one will give you an answer to this.

- And the second recommendation. I am just a man, I am not a doctor. What should I do? How can I support myself, how can I not die? I’m not going to sit at home for 18 months.

- Concentrate on preventive measures, but not treatment. Until it is clear that there are validated treatment measures that will help not to acquire the virus, or will help get rid of it quickly.

- That is, what should I do?

- That is, wash your hands, do not contact with others, keep a distance of two meters, do not visit crowded places, and so on. At the first signs of the occurrence of acute respiratory viral infection, which are progressing and burdened, consult a doctor.

- Well, that is, when you have shortness of breath ...

- Runny nose, cough, shortness of breath ...

- 38.5.

- Yes.

- Do not drink aspirin, but you need to call an ambulance.

- If you had suspicions of contacts.

- What do the contacts mean? With anyone already contacts, that's all. The virus in the population. Let's be honest about that ...

- To a certain degree of certainty, there is. But imagine, we are now in a season that, in principle, is overloaded with ARVI. That is, it is not a fact that the symptoms that you have, and most likely it will not be a fact, are associated with a coronavirus.

- That is, it can be any other ...

- Calling an ambulance for every case of acute respiratory viral infection - it is unrealizable, impractical for infrastructure.

- So, how should I understand if I have a coronavirus or have parainfluenza?

- Let's just say if a fever, and this is 38+, does not stop with routine methods for three days ...

- Ibuprofen.

“Ibuprofen, for three days, or you feel a progressive growing deterioration, that is, the cough is getting worse, it is still dry, maybe shortness of breath appears, and so on, then yes, ambulance.” Because the appeal is just to the doctor in the clinic ...

- It will lead to the fact that you will infect another 20 people around in this clinic.

- Yes Yes. And do not leave the house with these symptoms, preferably, of course. In general, one caregiver is recommended, in this case.

“That is, let him die with you.”

- That is, the sick person should contact only with one person. Everyone else should stop all contact with the sick.

- That is, do you think that all summer Russia will suffer from coronavirus or what?

- So shows the dynamics of the Chinese epidemic. And we cannot yet evaluate another dynamics, because the Chinese epidemic is the only epidemic that has reached that very recession and plateau, yes. In Italy everything is at its peak, everything is at its peak everywhere, we don’t know ... We have no other predictive models. We can appeal so far only to the Chinese.

- Thank you.

- Let's hope that everything will be fine. Take care of yourself. I did not voice another sad point.

- Which one?

- Coronavirus does not provide immunity. The property of a coronavirus is that, having been ill with a coronavirus ...

- No, I understand, you will get sick with it again.

- Yes.

- And why are we then talking about population immunity?

- There is hope. The summary is as follows. That still you need to follow the recommendations for self-isolation.