Eight months without curative treatment against covid and with no solution in sight

Eight months after the new coronavirus was identified in the Chinese city of Wuhan, there is still no effective treatment for the disease that has already killed nearly a million people worldwide, according to the most conservative death toll.

There is neither a silver bullet against the virus nor is it expected to appear in the short term.

“We are not too optimistic.

So far there is no curative drug for a respiratory viral disease.

There is no curative treatment for the flu or the common cold adenovirus.

There are no precedents.

It seems unlikely that we will have a curative drug for this disease in the near future, "says physician Ricardo Gómez Huelgas, president of the Spanish Society of Internal Medicine (SEMI).

During the first wave of the epidemic, about 86% of hospitalized patients in Spain received hydroxychloroquine, an old anti-malaria drug touted as near-miraculous by US President Donald Trump.

In 62% of the patients, a combination of two drugs indicated for the AIDS virus, lopinavir and ritonavir, was chosen, according to the SEMI registry.

Today it is known that those first treatments provided covid patients with little more than a glass of Agua del Carmen.

One in five admitted patients died in those chaotic months, but today the mortality rate is far from that 20%.

“We did treatments without scientific basis because we had no other option.

We have improved our knowledge of what does not work and what does work in some circumstances, ”says Gómez Huelgas, from the Malaga Hospital Complex.

One of the great advances is simple: turning the sick face down.

The SEMI registry includes 18,000 patients with covid in more than a hundred Spanish hospitals.

Gómez Huelgas, one of its coordinators, emphasizes that in the first wave, the patients were an average of 70 years old, suffered from other pathologies and came to the doctor too late.

They are now in their 50s, have better health and are treated much earlier.

The mortality of patients admitted in the second wave is below 10%, according to a preliminary estimate by Gómez Huelgas.

“It is not because the treatments have changed substantially.

The difference is that the patients used to be much older and had many underlying pathologies, ”he argues.

"It seems unlikely that we will have a curative drug for covid in the near future," says doctor Ricardo Gómez Huelgas

The doctor Carolina García Vidal, from the Hospital Clínic de Barcelona, ​​is more optimistic and shows her results.

“Almost all European hospitals reported a mortality of between 20% and 30% of patients with covid in the first wave.

We had a 12% mortality ”, he says.

García Vidal recalls the confusion of the first months, when the WHO changed its protocols to treat covid “every three days”.

"The mess of information overflowed the health system," he laments.

The doctor's team then designed an artificial intelligence system that helped offer personalized treatments to more than 2,000 patients admitted to the Clinic.

Doctors already see covid almost as if they were two diseases in one.

In the first stage, the coronavirus multiplies in the cells of the respiratory system and the first symptoms begin: fever, dry cough, general malaise.

The second phase begins when the virus invades the depths of the lungs and the human body responds by sending out a whirlwind of defensive cells, a response that can run wild and be even more dangerous than the virus.

"It is not a disease in which all patients have to be treated in the same way", warns García Vidal.

"Personalizing the treatment at all times is what ends up leading to success."

The scientific community is looking for effective antivirals for the first stage and drugs that modulate the immune response for the second stage.

The European health authorities have so far only authorized one antiviral drug against the coronavirus: remdesivir, initially developed against the Ebola virus by the US pharmaceutical company Gilead Sciences.

It is a controversial drug.

A complete treatment costs just over 2,000 euros and so far it has not been shown to reduce mortality from covid, according to the pharmacist Jesús Sierra, from the University Hospital of Jerez de la Frontera (Cádiz).

An international study with about 1,000 patients did show in May that those treated with remdesivir had a mean recovery time of 11 days, compared to 15 days needed for those who received an inactive substance.

The US has bought almost all of the drug's stock.

“Remdesivir is not the solution we expected.

And there is a risk that we think it is and we will not continue investigating ”, warns Sierra, who coordinates the registry of the Spanish Society of Hospital Pharmacy (SEFH), a database of 16,000 patients to identify drugs associated with lower mortality by covid.

“Now the fear is that the remdesivir will end.

What difference does it make if it's over if it hasn't been proven to work?

The concern should be to try new targets to see if we save lives, because we have a very long year ahead of us, ”says Sierra.

One of the most promising experimental drugs is MK-4482, an antiviral developed at Emory University (USA) that is administered in oral tablets and that would compete with the intravenous remdesivir.

“Remdesivir is not the solution we expected.

And there is a risk that we think that it is and we will not continue investigating ”, warns the pharmacist Jesús Sierra

Carolina García Vidal is convinced that remdesivir does reduce mortality if it is given too early, in that first phase in which the virus multiplies.

The doctor will present her results on September 17 at the I National Congress of Covid-19, an internet event in which fifty Spanish scientific societies participate.

"I think that one year from now it will be difficult for us to find a more effective antiviral than remdesivir," says García Vidal.

The desperate search for a covid treatment has practically just begun, but it is already full of failures.

The WHO launched an international trial in March, called Solidarity, to compare strategies against the covid.

On July 4, the organization warned that two of the most widely used treatments in the world - hydroxychloroquine and the lopinavir / ritonavir cocktail - not only did not work for hospitalized patients, but could even cause adverse effects.

The only drug that has been shown to save lives to date is dexamethasone, a corticosteroid synthesized in 1957 that relieves inflammation and lowers the immune system response.

The drug costs only a few cents a day and reduces the risk of death for the most serious patients by a third, according to data from Recovery, a clinical trial in 175 UK hospitals.

These results, published on June 16, came too late for many patients.

Jesús Sierra estimates that in Spain "35% of hospitalized patients should have received corticosteroids and did not receive them," according to his registry.

The Spanish pharmacist misses more well-organized clinical trials, such as Recovery itself, a project promoted by the University of Oxford in which the results of some 11,500 patients are compared.

In Spain, some 120 trials of potential treatments against covid have been launched, according to data from the Spanish Agency for Medicines and Health Products (AEMPS).

“It is a very high number, undesirable, illogical.

In Spain, very local initiatives have been carried out, when the logical thing would have been to carry out centralized clinical trials, to which hospitals would join.

We are like islands, the whole world is isolated ”, explains Sierra.

"You have to do self-criticism and ask yourself if you would need a centralized public research structure that would allow you to carry out your own tests in an agile way," he reflects.

35% of hospitalized patients in the first wave should have received corticosteroids and did not receive them

"It is highly desirable that we group together, not only in national studies, but also worldwide," agrees doctor César Hernández, head of the Department of Medicines for Human Use of the AEMPS.

Hernández recalls that his agency supported the implementation of the WHO Solidarity trial, in which some 40 Spanish hospitals participate.

“You have to do more cooperation and less competition.

And those who have to lead this cultural change are the researchers themselves.

There are times when, even within the same institution, it is difficult for two different departments to agree.

These barriers must be overcome ”, prompts the doctor.

Hernández emphasizes the scientific evidence of current treatments: remdesivir shortens recovery by four days and dexamethasone prevents a third of the deaths of the most serious hospitalized patients.

That is all that has been shown at the moment.

"I am quite waiting to see what results the monoclonal antibodies against the coronavirus give, because they could be a highly effective treatment," says the doctor.

Monoclonal antibodies are one of the great hopes against covid.

People who have overcome the disease have specific proteins, called antibodies, in their blood plasma that have helped neutralize the coronavirus.

The simplest strategy would be to perform plasma transfusions directly from survivors to the sick, but it is not known if this works.

In the US it has been done with tens of thousands of patients, but without comparing the results with another control group that did not receive the transfusion.

In Spain, a first study with 83 patients does suggest that plasma improves the prognosis of less seriously ill patients, but the results are not conclusive.

The idea of ​​monoclonal antibodies goes further.

It consists of isolating specific antibodies from blood plasma to produce large quantities of synthetic clones in the laboratory.

The strategy is being very successful against some types of cancer, as shown by trastuzumab, one of the most effective drugs against aggressive breast tumors.

Against viruses, however, the technique is in its infancy, except for an injection of monoclonal antibodies, called palivizumab, to prevent pneumonias in babies caused by the respiratory syncytial virus.

The American biotech company Regeneron has received $ 450 million from federal authorities to boost its cocktail of REGN-COV2 monoclonal antibodies, already in trials with thousands of people to see if it is capable of treating or even preventing COVID.

There are dozens of private companies and academic laboratories around the world competing to develop monoclonal antibodies as soon as possible, drugs that would in any case be expensive and difficult to produce.

“Whatever the tipping point in the treatment of covid [...], we will have to strive for equitable access.

We know that not all the answers can be found in the offices of the pharmaceutical industry ”, warned Julien Potet, from Doctors Without Borders.

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