New Covid-19 drug saves seriously ill patients and hurts others (Upd. And Upd.2)

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New Covid-19 drug saves seriously ill patients and hurts others (Upd. And Upd.2)
New Covid-19 drug saves seriously ill patients and hurts others (Upd. And Upd.2)
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Dexamethasone, a popular steroid, proved to be the first known effective treatment for reducing mortality in severe coronavirus patients. The reason, most likely, was its ability to suppress the work of the immune system. The researchers who discovered the effect are confident that if the drug had been used since the beginning of the epidemic, it would have saved many lives. However, given the persistence of the epidemic in many countries, including Russia, the drug can still play a huge role in the treatment of people.

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The coronavirus pandemic has killed more than 440 thousand people to date, and, according to a number of indirect signs, the real figure may be significantly higher. In most cases, a seriously ill patient does not survive even with mechanical ventilation.

Attempts to reduce the severity of the problem with some drugs with antiviral activity have shown mixed results. While a number of studies have pointed to the effectiveness of remdesivir or hydroxychloroquine, others have said they are useless or even harmful.

True, at least one revealing study, when checked in detail, turned out to be based on fake data - from a commercial firm that traded statistics on the epidemic, "saving" on the actual collection of such statistics.

New candidate: steroid hormone that suppresses immune function

However, now, during the RECOVERY Trial, conducted in the UK, for the first time, a different result has been achieved: in a relatively large sample of patients, it was possible to reliably show that the survival rate of coronavirus victims in the case of the use of one well-known drug does indeed increase. We are talking about dexametozone (approximate formula C22H29FO5). It is a synthetic steroid hormone that has a versatile effect on the human body.

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In a study of the effect of this drug on humans, a main group of 2104 patients participated: they were given six milligrams of dexamethasone per day for ten days. In addition, another 4321 patients received conventional treatment without this drug.

As a result, mortality among patients with severe disease who took dexamethasone decreased markedly. Those on the drug who received non-invasive oxygen (a tube near the face) died 20% less often than the same people who did not receive the steroid hormone. Patients on mechanical ventilation (a more severe form of the course of the disease) died 35% less often than similar patients not taking dexamethasone.

It should be noted that patients who had a milder illness - hospitalized, able to breathe normally without mechanical ventilation and oxygen - may even be harmed by the drug. The mortality rate among them was 22% higher than among those who also did not need oxygen and mechanical ventilation, but did not receive this steroid hormone. True, the statistical reliability here is somewhat less than for positive results: the number of deaths among lung patients is lower, and for this reason it is more difficult to collect statistics of the required volume among them.

A press release from the RECOVERY Trial team adds that "giving this medication to eight ventilated patients can prevent one of them from dying, and the same is true for 25 patients given oxygen."But this is a conservative, minimal estimate: most likely, the real effectiveness of the drug is higher.

The researchers limited themselves to such a verbal assessment because dexamethasone showed different effects on mortality for different groups of patients. For example, for ventilated patients, the reduction in mortality ranged from 52% for some groups to 12% for others. Saving one out of eight is the lowest bar for drug efficacy. Since the scientific work from clinical trials has not yet come out, it is not clear what was the difference between these subgroups of patients.

The study had a number of strengths and individual weaknesses. Patients did not know if they were receiving a new drug, which meant that the likelihood of a placebo effect was extremely small. The sample of both groups - both the main and the control - was large enough, that is, the results are reliable.

Weaknesses of the study include the fact that some of the patients received dexamethasone in tablets, while others received injections, while, based on the text of the press release, at the same dose (six milligrams per day).

However, the absorption of active substances from tablets is often far from 100%, that is, those who received the tablets could de facto take a lower dose of dexamethasone. In this regard, the effect of the drug for different patients can vary significantly.

The second weakness of the work - although not from a scientific point of view - is that it could cause the death of some patients who were given dexamethasone. Among those who could breathe on their own, without mechanical ventilation and oxygen, mortality while taking the drug increased by 22%.

In clinical trials, 41% of all patients who received mechanical ventilation died, 25% received only oxygen and 13% of those who could breathe themselves. Thus, a 22% increase in mortality in the last of these groups killed fewer people anyway than saved as a result of a decrease in mortality in the first and second groups.

Why did the drug increase mortality among patients with milder Covid-19?

The question arises: why does the same steroid hormone threaten death for a patient with a milder form of coronavirus infection, but helps serious patients?

Experts who conducted the tests do not yet give an answer to it: the corresponding work is only being prepared for publication. Nevertheless, it is biologically understandable. Dexamethasone (like some other steroid hormones) has a depressing effect on the immune system. In particular, it inhibits the formation of T-lymphocytes, as well as the migration of B-cells of the immune system and the interaction of T- and B-lymphocytes. In addition, it significantly inhibits the release of cytokines from lymphocytes, as well as reduces the formation of antibodies.

Cytokines are small molecules that act as transmitters of information in the body. They are secreted by cells of the immune system, and when cytokines touch the surface of ordinary cells, they activate a number of reactions in them.

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If there are too many cells of the immune system in the focus of coronavirus infection (which is typical for seriously ill patients), then cytokines that get on the surface of a neighboring immune cell force it to produce its own cytokines more strongly. As a result, the concentration of these molecules rises so strongly that a cytokine storm sets in.

The concentration of cytokines in this case becomes so high that ordinary cells that are not related to immunity begin to massively participate in the protective (normal) process of inflammation. It becomes systemic and so strong that a person's internal organs may begin to fail and he will die, even though the infection itself does not threaten his life.

In patients at a young age, immunity copes with the coronavirus quite well, so that it rarely comes to a cytokine storm. Therefore, the suppressive release of cytokines dexamethasone is unlikely to help such patients. At the same time, by suppressing the functioning of the immune system, it reduces its chances of effectively fighting infection.

In severe coronavirus patients, immunity with Covid-19, on the other hand, is already working too hard - due to the fact that it "overcovers", and a cytokine storm is playing out. In such conditions, the weakening of the activity of the immune system is more likely to benefit the patients: they do not risk getting all the disadvantages of the cytokine storm, which is often fatal for them.

It follows from this that it is unwise to stock up on a new drug in advance. Most people get Covid-19 in a relatively mild form, that is, dexamethasone can seriously harm them, significantly increasing the risk of death (oddly enough, it is possible even without serious breathing problems).

Those who get on mechanical ventilation, in any case, will receive a remedy as prescribed by a doctor. Moreover, dexamethasone is a cheap and massive generic drug, the deficit of which is extremely doubtful.

What could be the global effect of dexamethasone in a pandemic

Despite the fact that the coronavirus is gradually leaving the focus of public attention, the scale of the epidemic itself is still enormous. In the United States, until the last days, 20 thousand new cases were registered per day. In Russia, outside Moscow, the number of new coronavirus patients hovers around seven thousand per day - that is, not much lower than the peak, which has so far been overcome only in the capital.

The coronavirus has shown all the signs of seasonality: it rages most strongly where temperatures are below local norm. For example, in Brazil, where it is winter now. Therefore, it is obvious that in the fall of 2020 and in the winter of 2020-2021, it can give a very strong second wave - like the "Spanish flu" once did. To date, 0.44 million people have died from the epidemic, and by autumn this number will noticeably exceed half a million. With the second wave, the death toll could be well over a million.

This means that dexamethasone can save many lives. British researchers believe that if this tool were used in England at the beginning of the epidemic, it could allow at least five thousand people to survive - about one in nine who died from the virus in this country.

Thus, during the current sluggish epidemic process, as well as during the autumn second wave, dexamethasone can potentially save many tens of thousands of lives.

Upd.: UN World Health Organization calls Covid-19 treatment with dexamethasone "scientific breakthrough". It is especially noted that this is the first known drug that reduces the mortality rate of coronavirus patients connected to mechanical ventilation by up to 30% or more.

Tedros Ghebreyesus, WHO Director-General, said in this regard: "This is great news and I congratulate the UK government, Oxford University and the many hospitals and their patients who have contributed to this life-saving scientific breakthrough."

Upd. 2: The new clinical trial was also responded to in Russia. Head of the Department of Pulmonology at Sechenov University and Chief Pulmonologist of the Ministry of Health Sergei Avdeev said that dexamethasone is used to treat covid patients in our country, moreover, it is included in the guidelines for the treatment and prevention of COVID-19. But, alas, it cannot be called a panacea, the specialist added.

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