Hydroxychloroquine and chloroquine were among the first drugs empirically used for the treatment of COVID-19. At the same time, several trials have begun to objectively evaluate their effects on Sars-COV-2 infection but produced inconsistent results.
Chloroquine is commonly used to prevent and treat malaria and amoebiasis,
while hydroxychloroquine, a less toxic metabolite of chloroquine, is used to treat autoimmune diseases, such as systemic lupus erythematosus, arthritis rheumatoid and Sjogren’s syndrome.
Antiviral activity of Chloroquine had already been reported in the past through in vitro experiments, showing that it was able to inhibit the growth of a variety of viruses, including the SARS-CoV-1 and SARS-CoV-2 coronaviruses.
The exact mechanism underlying the antiviral action of these two drugs has not been well defined, but it has been shown that they can increase the pH of the endosomes that the virus uses to enter cells, destroying them.
In addition to the effects on cellular pH, Chloroquine can affect viral replication by inhibiting viral gene expression. The two drugs are in fact able to interfere with the glycosylation of the angiotensin 2 converting enzyme, which is the cellular receptor where SARS-CoV virus binds, and associated gangliosides.
A new study, published in the New England Journal of Medicine, seems now to remove all doubts, showing that the administration of hydroxychloroquine in patients hospitalized for Covid-19 does not reduce mortality at 28 days.
This randomized, controlled, open-label trial, evaluated hospitalized patients with Covid-19. They were assigned to receive hydroxychloroquine or usual care. The primary endpoint of the study was mortality at 28 days.
The mean age of the patients was 65 years, and the majority were males. About 60% of them received only oxygen, while invasive ventilation was adopted in 17% of cases.
The lack of efficacy of active treatment against the study endpoint was so evident that the researchers decided for an early closure of enrollment.
Mortality at 28 days occurred in 27% of patients on active treatment and in 25% of those assigned to usual care.
Patients in the hydroxychloroquine group had a longer hospital stay than those in the control group, with median durations of 16 and 13 days, respectively. Furthermore, they were less likely to be discharged alive at 28 days.
Considering patients who were not undergoing invasive mechanical ventilation, the secondary composite endpoint of invasive mechanical ventilation or death occurred more frequently in the active treatment group.
Regarding the safety of treatment, the authors report a small numerical excess of cardiac deaths among patients treated with hydroxychloroquine, but no difference in the incidence of new major cardiac arrhythmias.
Just when a recent study seems to endorse the efficacy of an antiviral drug like remdesivir in the treatment of COVID-19, this new research on hydroxychloroquine seems to preclude its use for this disease.
Hydroxychloroquine did not reduce mortality to 28 days, compared to usual treatments, showing a clear lack of efficacy in this sense.
However, the authors point out that these results indicate that hydroxychloroquine is not an effective treatment for hospitalized patients with Covid-19 but does not concern its use as a prophylaxis or in patients with less severe forms of SARS-CoV-2 infection. Hence, a door is left open for its possible use in other clinical settings, in which, however, its usefulness is far from being demonstrated.
In this frantic series of researches that try to shed light on the drugs that are truly effective in the treatment of COVID-19, reliable information needs to be selected and implemented in the guidelines for the disease.
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