Dr. Botev, you are part of the team testing a new treatment for COVID-19 with surfactants. First, please explain how you came up with the idea to treat the coronavirus in this way?
- As a matter of fact, we came up with this idea quite by accident when I was in "Sofiamed" hospital and we had to transfuse a patient with convalescent plasma.
He was in extremely serious condition. While discussing with Dr. Vasilka Zarcheva how effective a plasma transfusion would be for this patient, she suddenly thought that surfactant therapy could help this person.
I supported Dr. Zarcheva's idea and after making a bibliographic reference, we found out that this method is already used to treat the coronavirus infection in several countries and gives exceptional results.
There is also a comment from my colleagues from Russia who also apply it and share that they also achieve such good results. It is mainly applied in England, France and the USA. It is now being done in the form of clinical trials because all the therapies are new for this disease. The results of surfactant application have been very good so far.
We decided to go in this direction and apply surfactant in the treatment of this patient due to the fact that the mortality rate is very high in people who reach respiratory failure.
Regardless of the relevant apparatus ventilation, their condition does not recover. As a result, other organs and systems are damaged. These patients are only 5%, but their mortality is 100%.
After we applied it, there was an improvement in respiratory function. It has been established that even if the alveolar cells are damaged by the virus, when surfactant is applied they improve their functional activity.
What are surfactants? How exactly do they turn into medicine?
- Surfactant is a protein, lipid mixture that is produced in the pneumocytes of the lung. They are made of 23-pentapeptides, and the virus has 13 pentapeptides that match them.
Surfactants are generally substances that reduce the surface tension and destroy the envelope of the virus - they work this way. For example, few people know that soaps with surfactants are therefore able to wash hands.
But in the case of the coronavirus, the surfactant has another advantage - it exhibits very strong antiviral properties. It consists of four parts, peptides A, B, C and D, with A and D being fat soluble and binding it, effectively killing it.
Separately, there are three proven mechanisms by which this product destroys the coronavirus. One is with macrophages, the second is direct killing, and the third is interacting with other cells.
Are there surfactants in our body?
- There is a surfactant in every person. It helps the lung to breathe. In fact, surfactant is what keeps us safe from various viruses. In children, they are in a much larger amount, but it decreases with age. And this is one of the reasons why older people get sick more severely from any viral diseases.
They exist, of course, in other forms - one is synthetic, and the other is obtained from animals - from pig or beef lung.
Surfactant treatment is very expensive. Therefore, together with the National Patient Organization and their program for the treatment of the coronavirus with convalescent plasma, for which I am a consultant, we will try to help the sick by collecting donations.
One vial costs BGN 1,050, and the standard treatment includes three to five vials.
In fact, until the condition improves, more may apply. So far, it has been found that only cases with sepsis do not respond to this therapy or if the treatment is given too late.
Our team has also developed an algorithm of tests with which we can prove whether the patient has a surfactant deficiency. And if the surfactant is included within 24 hours of placing the patient on mechanical ventilation, improvement can be achieved after only three applications.
What stage of the trials are you at and when do you expect the new therapy to begin?
- It is already applied in many places, even at home. There is also a part that takes the form of a clinical study, where the problem is that every patient must go through a committee on medical ethics.
There are two preparations that increase surfactant and a clinical trial is currently underway to treat the coronavirus. And these are well-known preparations - bromhexine and ambroxol. The results we are getting so far are very good.
Otherwise it is very easy to tolerate. Especially in the earlier stages when it is used, the effect is immediate. I have done research on the patients in whom I applied surfactant treatment.
One can see how immediately the virus load decreases, the antibodies begin to fall and the entire process asset decreases. That is, we have also studied people in whom the effect of the treatment is clearly visible.
- You say that the treatment of the coronavirus is complex. Which methods have been approved to date?
- To date, there is only one approved drug for the first phase of development of the coronavirus infection - remdesivir.
The second one is with convalescent plasma, approved in principle for emergency use in such a crisis situation. Once more data is collected on it, it will be fully approved. There are six other antiviral drugs, but some of them are very weakly effective, and others shorten the hospital stay by only one day.
Do you find that 80% of patients are treated incorrectly with plasma therapy? What are the main mistakes that are made when applying it?
- Basically, regarding plasma therapy, when the most important clinical trial of the “Medical Mile Clinic” was performed in the USA, they did not know and did not report the antibody titer. It is now known that for the therapy to be effective, it must be applied from the first to the third day, when the condition worsens, in order for the patient to receive a high titer of antibodies.
And the other big mistake that is already observed is the application of the convalescent plasma during the second stage of the development of the infection, when there are coagulation changes. There is a complement in this plasma that gives very good results.
The problem is that it overflows without needing it. In these cases, ordinary plasma can also be used, which is much more affordable and has much greater qualities available.
How affordable is plasma treatment outside of Sofia? Can every patient in Bulgaria indicated for this treatment actually receive the therapy?
- Treatment is affordable and easy to find even outside of Sofia, the problem is that it is poorly organized and ambulances travel alone.
And there should be a depot for receiving plasma in every blood center, so that the ambulance does not have to travel from one city to another. It's a huge waste of time because sometimes it's a life saver.
In case of rapid involvement of the lung, as was the case with a colleague from the Black Sea, who unfortunately died, it must be transfused immediately - within 24 hours for the treatment to be effective. This colleague was for treatment with surfactant and such plasma - high titer.
In 20% of patients with this disease, the infection continues down to the lung. And it is good to treat these patients with plasma, especially for the risk groups - the earlier, the better. But due to the shortage of the product, it has become customary to apply it when the patient shows signs of deterioration.
After the avalanche of people infected with the coronavirus every day, is the number of people willing to donate plasma increasing?
- Yes, there are more and more people who want to donate. The problem in this regard is that there are only two centers where convalescent plasma can be donated, and they are in Sofia.
If they wish to do so, patients from the country must travel to the capital. Fortunately, there are now non-governmental organizations that say they will cover the travel expenses of such donors. But it definitely makes it difficult to donate.
I want to point out one more advantage of donating plasma, apart from the desire of those affected by the coronavirus to help.
Those who donate plasma are also cleared of antibodies that can cause autoimmune diseases. It has already been proven that 40% of severely ill patients then develop autoimmune diseases within two years - autoimmune bodies appear.
Which autoimmune diseases do you mean exactly?
- For example lupus, multiple sclerosis. There are anti-brain, anti-mitochondrial and anti-muscle antibodies… In general, very severe and unpleasant diseases.
Generally, when one autoimmune disease occurs, it is always easier for the second to develop. The severe reaction to the coronavirus infection is autoimmune. Antibodies are formed against the compliment.
How is convalescent plasma different from regular plasma?
- COVID-19 should be considered in several stages. The first is prophylactic, with a certain approach. In the second case, the viral disease must be treated.
Next comes the autoimmune or coagulation stage and finally the late effects. Regarding the first step, it is clear that plasma that contains antibodies is effective and many other therapies are based on it. There are 30 types of virus-neutralizing bodies in plasma.
There are already two types of plasma therapies for coronavirus. The first type - the so-called ordinary plasma, kills the virus, and the second solves the coagulation problem because it adds complement. And basically, when plasmapheresis is done, one of the complements damages the tissues.
So the best therapy in the second stage, when people die from blood clots, is plasma, which saves 40% of patients, and plasmapheresis, which can reach an effect of up to 90%. That is, to save those people who are now dying at 100%.
This is the latest in treatment for the coronavirus. And the other new thing is that the disease is microthrombotic - microangiopathy develops.
Thus, the coronavirus infection enters the group of other similar diseases such as catastrophic antiphospholipid syndrome, HUSK, hemolytic-uremic syndrome, atypical hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura or Moshkowitz's disease and IK. These are some of the most serious conditions in medicine. And it's already a new kind in clotting
The condition is successfully treated with plasma and the results are very good. But since there is not yet a large volume of application of the method, the results are defined as primary.
Should be done on a few thousand more people to get a method approved. And that's why emergency centers should be organized to receive plasma, because the needs will become huge from it.
Not to be donated by donating blood, but by plasmapheresis, as convalescent plasma is obtained. A donor can then give much more plasma to meet the huge demand for it. Now at the moment one donor gives blood and some plasma - about 200 ml.
This is the latest trend in treatment, as this disease leads to blockage of the smallest vessels - thrombotic microangiopathy. It affects all organs and systems.
And the peculiarity of this blockage is that others run with normal or low fibronigen, while here the fibronigen is much higher, which is due to the inflammation from the virus, and therefore it runs very unpleasantly and with high mortality due to severe complications.
Here I must say that one of the clotting factors is fundamental - it is called complement. And one of its forms directly damages tissues. This is a new discovery as a possibility of tissue damage.
Could you explain more accessible about this new tissue damage?
- The problems are that in this disease one of the clotting factors plays a leading role - it is called complement. And one of its fractions has a direct damaging effect on tissues. That is, when activated, it begins to damage any tissues very seriously.
They, in turn, damage the vessels and hence all the organs. This fraction is activated by the virus, distorting the entire clotting process and going by a much different mechanism.
Turns out the virus is now much more contagious but less deadly. This explains the high number of infected people. Is a new strain of the virus spreading now?
- This is the information we have. It is based on Western literature. It mentions that one amino acid has been replaced by another in the structure of the virus.
The new strain is not only in Bulgaria, it is also spreading throughout Europe. Therefore, there is a difference in the course of the pandemic now and before. It's not just because of the measures to protect against the virus.
It's a matter of biology - the new strain has mutated because there was a limit to its spread by wearing the masks.
And he has managed, somehow, to become much more virulent and conquer the territory that has become vacant. That is, wearing masks has provoked the development of the virus in this direction - to overcome this problem, purely evolutionary. And that's why the strain that happened by accident has managed to become so successful for itself.
Recently, we notice that young people who do not have accompanying diseases are losing the battle with the virus…
- They develop exactly this type of disease where the mortality rate is simply high. So far, therapy has been more about prevention. The real therapy is with plasma and plasma exchange, through plasmapheresis.
Among all this information about the coronavirus, what do you think are the most effective weapons against infection besides masks and frequent hand washing?
- Prevention is most important. Probiotics specifically do a very good job because this is a disease related to gut bacteria, especially for hemolytic uremic syndrome and atypical HUSK.
It has also been proven with the coronavirus that if your bacteria work well, the body copes with viral diseases. And separately, you can drink bromhexine for a short time, which increases the surfactant to fight the virus too.
That's why people who suffer from asthma and those with chronic obstructive disease who take it prophylactically get almost no coronavirus, which is a surprising, even paradoxical reaction.
Vitamin D also increases the amount of surfactant. But before you start taking it, it is better to measure its levels in your body. Its amount in the blood should be 75 nanograms. This is the optimal value.
In addition, an awful lot of antibiotics are prescribed in Bulgaria, which rather has a damaging effect. They are prescribed for a certain time, in the presence of infection, and not prophylactically - in the early stages of the coronavirus infection.
This leads to very serious complications at a later stage. Antibiotics destroy the microflora and along with it - the body's defenses.
