SCIENCE

Fighting Covid-19: The pioneers of dexamethasone in Spain

Spanish doctors have been using this corticosteroid medication on patients on ventilators and oxygen support since March. But while it is justified for the critically ill, it can be dangerous for others

Ana Fernández Cruz, a specialist in infectious diseases at Puerta de Hierro hospital in Madrid.
Ana Fernández Cruz, a specialist in infectious diseases at Puerta de Hierro hospital in Madrid.Andrea Comas

Most Covid-19 deaths are not so much due to the coronavirus itself as to the immune reaction it can trigger, at times involving severe inflammation leading to the respiratory failure that ends up killing so many elderly patients or those with underlying medical conditions.

The first drug shown to prevent deaths from Covid-19 targets this stage in the disease’s development. Dexamethasone is an anti-inflammatory medication that also inhibits the response of the immune system, bringing down inflammation and managing to save the lives of two of the most severely affected groups – those who need ventilators and those who need oxygen, according to preliminary results released on Tuesday from a large clinical trial carried out in the United Kingdom. Rather than fighting the virus itself, dexamethasone combats the exaggerated immune response to it.

Spanish doctors and scientists were among the first to draw attention to the fact that this drug can save lives. On March 11, a team at Madrid’s Puerta de Hierro hospital began giving dexamethasone to those already on a ventilator, explains infectious disease specialist Ana Fernández Cruz. They also gave them methylprednisolone, another very similar steroid. “When we saw it was working, we also used it for less serious cases that only needed oxygen,” she says.

Rather than fighting the virus itself, dexamethasone combats the exaggerated immune response to it

On May 26, after analyzing around 400 patients, the Puerta de Hierro team released the results of a preliminary study due for publication in a scientific journal. This study found that the drug reduces mortality by 41%. According to Fernández, prior to this, there had only been a few studies published on the matter, involving a small number of patients in China. These analyses also indicated that the medication reduces mortality among patients in serious condition.

The findings from the Puerto de Hierro trials support the conclusions of a UK trial that involved giving half the amount of dexamethasone given by Fernández’s team to more than 6,000 patients in 175 hospitals; that this drug reduces the risk of death in assisted-breathing patients by a third and in those who need oxygen by a fifth. This is the group most at risk of dying of Covid-19. “Based on the data, the drug should be given to all patients in a similar condition to those in the study,” says Fernández.

“Those responsible for the British trial have said that this drug is capable of saving lives, and its use would be justified in prescribed cases during a pandemic like the current one,” said Jesús Villar, a researcher in respiratory diseases at the Doctor Negrín University Hospital in Las Palmas de Gran Canaria, in the Canary Islands.

This drug can cause infections, diabetes, osteoporosis and gastrointestinal bleeding. It cannot be used indiscriminately
Ana Fernández Cruz, infectious disease specialist at Puerta de Hierro hospital

Villar is himself coordinating a clinical trial with dexamethasone in severe Covid-19 patients in 17 Spanish hospitals, using a slightly higher dose than was used in the UK.

The trial started after his team published a study in March that showed this drug reduces mortality from acute respiratory distress, a serious inflammatory reaction that affects the lungs due to infections very similar to that produced by the new coronavirus. “If these results are confirmed, you have to give the drug to all the patients in these circumstances,” he says. “You can no longer have a control group that doesn’t receive it.”

The question now is when to administer the drug. “Usually the peak phase of inflammation occurs within about 10 days after the onset of symptoms, though it does not occur in all patients,” says Fernández. “If this excessive inflammatory response can be controlled, especially when a large part of the lungs is still intact, it can benefit the patient.”

The news is especially good because of the price and general availability of the drug. A dexamethasone treatment, which was discovered at the end of the 1950s and is widely used to treat severe allergic inflammatory reactions and autoimmune diseases, costs between €1 and €2 a day, according to Cristina Avendaño, a pharmacologist from Puerta de Hierro.

The news is especially good because of the price and general availability of the drug

The findings come after several studies on possible treatments for Covid-19 have been abandoned due to unreliable data, as with the anti-malaria drug hydroxychloroquine. Although the data from the British trials on dexamethasone are preliminary, the experts consulted by EL PAÍS believe they are reliable, partly because the study is backed by the National Health Service in the UK and partly because it is a randomized evaluation – there is a random selection of which patients will receive the drug and which ones will not – with a control group that allows doctors to determine that the observed benefits are due to the medication and not something else.

“It is entirely possible that this drug is effective, but it is important to select the patients correctly because corticoids inhibit the immune system, so we have to find an appropriate balance between decreasing inflammation and not increasing the viral load,” says África González, the outgoing president of the Spanish Society of Immunology.

The drug only works for critically ill hospitalized patients and can be very harmful for others who are less severely affected by the disease. “Just as it is an effective drug with great anti-inflammatory power, it also has a multitude of side effects such as infections, diabetes, osteoporosis and gastrointestinal bleeding. It cannot be used indiscriminately,” warns Fernández.

In any case, according to Fernández, until there is a vaccine that can be administered to the general population, the war against the worst pandemic so far this century will not have been won.

English version by Heather Galloway.

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