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Hydroxychloroquine is raging in the media. (Photo: Dercilio / HEALTH is Vital)
Prevent Senior announced long ago that it would conduct research on Co-use of drugs hydroxychloroquine and azithromycin in the first days of symptoms after infection with the new coronavirus (Sars-CoV-2). The results have just come out and indicate a reduced need for hospitalizations after this treatment.
But the study’s methodology received harsh criticism from two scientists heard by HEALTH. According to both, the indicated results are not reliable and should not be used as an argument to use this combination against Covid-19.
A summary of the study itself.
Patients treated by Prevent Senior who were at home, but had suspected symptoms of Covid-19, the disease caused by the coronavirus, for more than three days, were invited to participate in the experiment. In total, 636 volunteers, with an average age of 62 years, accepted.
The hydroxychloroquine and azithromycin combo was offered to all: 412 agreed to receive home treatment, while 224 refused. All were monitored daily by telemedicine.
Result: 1.9% of the group that took the pills required hospitalization, compared to 5.4% of those who did not ingest them (2.8 times more). The benefits would be greatest when participants started treatment before the seventh day of symptom onset.
“In this first moment, we focus on the effect on the hospitalization rate because we understand that this is a major coronavirus problem. This is because it brings a considerable number of people to the hospital, which can overload the health systems, ”defends Dr. Pedro Benedito Batista Junior, executive director of Prevent Senior. “A treatment that reduces this rate would go a long way in fighting the pandemic,” he concludes.
The study has not yet been published in a scientific journal. This means that it has not been subjected to a technical evaluation by other specialists, who could point out limitations, errors and adjustments.
During the current pandemic, it is increasingly common to see the diffusion of research before this scientific Saturday, so to speak. That’s why we asked two independent researchers to evaluate the article published by the Prevent Senior team.
The issue of coronavirus diagnosis
The recruited volunteers, regardless of how they presented symptoms such as cough, fever and tiredness, were not subjected to molecular tests to confirm the presence of Sars-CoV-2. “Some of these people could have the flu. Virological diagnosis is mandatory to discern the effectiveness of an antiviral drug, ”criticizes virologist Paulo Brandão, from the University of São Paulo.
According to him, conducting an experiment with a “probable diagnosis” only creates uncertainty. “For me, this would be a reason to deny publication of this study in a scientific journal,” he concludes.
Natalia Pasternak, biologist and president of the Institute of Sciences, agrees. “We don’t know if they treated Covid-19, or if they were treated for the flu, cold, allergic rhinitis, asthma,” he lists.
The question of volunteers.
Research traditionally used to ensure the effectiveness of a treatment randomly divides participants between the group undergoing medications and those who serve as controls. In the Prevent Senior research, the volunteers themselves chose the group they wanted to be in.
“This creates a bias. The person may have chosen to take the medicine because they believe so much in it. And the placebo effect has power, “says Natalia. She also remembers that the impact of the media on hydroxychloroquine and azithromycin is huge, which would contribute to the placebo effect.
In addition, the volunteer may have agreed to receive treatment because he has slightly more intense or prolonged symptoms: he would be more willing to try a drug without scientific evidence to avoid hospitalization.
“But the presence of more symptoms could mean that the coronavirus has infected this individual longer, and therefore would be closer to being eliminated by his body,” he adds. If that were the case, you would have a greater chance of not being admitted, because your body would have passed the critical stage of infection.
In other words, the way in which volunteers are recruited and the fact that they choose which strategy to follow raise doubts about the reliability of the research result.
According to Natalia, it would be possible to resolve these limitations by making a random division between the groups and offering a group a placebo treatment, without any volunteers knowing what they are taking and no doctor knowing who received and who did not receive hydroxychloroquine or azithromycin. .
Work is being done right now. “But we want to offer faster responses to the population with this article,” argues Rodrigo Barbosa Esper, a doctor who led the Prevent Senior investigation. He says his own team is participating in stronger surveys.
Virologist Paulo Brandão also criticized the great difference in the number of people in each group: 65% of the volunteers received the medicine. “Huge discrepancies in this regard decrease confidence in the evidence,” he says.
Esper responds: “We did not want to exclude people who took the treatment from the study because of a methodological issue and for not being criticized for actively selecting the chosen ones.”
According to Natalia, a solution would be to draw, among the treaties, who would be considered and who would not be considered for the investigation. This would eliminate the need for an active choice of researchers, while equalizing the number of participants in each class.
The question of the benefit of treatment
The work indicates a reduction in the number of hospitalizations in people with suspected coronavirus infection. “But we don’t know what happens from there,” says Natalia. In other words, the person may have entered the hospital one day and left the next. Or they have been intubated. Or, unfortunately, he died. Knowing this information would help verify the actual effect of taking hydroxychloroquine and azithromycin.
The president of the Questão de Ciência Institute also states that since the doctors knew who received the medications, they might tend to believe that these people would be more protected from the complications of Covid-19. And with that, they would request fewer hospitalizations. Returning to the same side, professionals could also request more hospitalizations from the group that did not take the medications.
“We have a clear indication of when to admit patients,” says Esper. Two criteria are cited in the article: oxygen saturation below 90% and overall worsening of health status (no further details on this criterion).
Paulo Brandão disagreed with the excerpt in which the Prevent Senior article states that no serious side effects were found. “In 16.5% of the treated cases, diarrhea was observed. Elderly people weakened with this problem can quickly become dehydrated, “he says.
Hydroxychloroquine, compared to chloroquine, actually has fewer adverse reactions with prolonged use. That is why people with chronic diseases, such as lupus, turn to it and not to chloroquine. “But even hydroxychloroquine can cause cardiac arrhythmias, which must be considered,” adds Natalia.
In addition to this research, many others have been performed to evaluate the effectiveness and safety of various treatments considered promising against the coronavirus. There is as yet no study testing the potential of hydroxychloroquine and azithromycin, either in patients beginning to show symptoms or in those with severe cases. Prevent Senior’s own article concludes: “There are as yet no randomized, double-blind, placebo-controlled studies testing the effectiveness of these drugs in the treatment of Covid-19.”
