In January 2020, chloroquine was one of the first medications offered as a therapy for COVID-19. It could be distributed quickly and at scale because it is a licenced medicine with a well-established safety profile and an existing production technique. It was removed from three large therapy trials in June. What exactly is the science behind these occurrences?
Why did we investigate chloroquine as a possible treatment option?
Before drug-resistant parasites became common, chloroquine phosphate was widely used to treat falciparum malaria in the 1980s and 1990s. Adding a hydroxyl group to the molecule produces hydroxychloroquine, which has been shown to be less hazardous in animal experiments and is used to treat inflammatory diseases including rheumatoid arthritis in Europe and America. Chloroquine is widely absorbed by body cells, resulting in an alkaline environment that inhibits virus multiplication. Both medications were found to block the novel coronavirus from entering and replicating in monkey cells cultivated on laboratory plates early in the epidemic. [1] [2] Several treatment trials were started in China, but due to the rapid local control of the epidemic, they were unable to recruit enough patients to firmly determine the value of chloroquine. [3] [4]
In March, researchers at a hospital in Marseille cited laboratory studies that showed chloroquine could protect monkey cells from infection with the coronavirus that caused SARS in 2003[5], and they began to give hydroxychloroquine to COVID-19 patients who were hospitalised. Twenty-six individuals agreed to take the medicine, and they were compared to 16 patients who said no. After six days of treatment, 70% of hydroxychloroquine-treated individuals had removed the virus from their nose and throat, compared to only 12% of controls. [6] Despite the fact that the experiment was tiny and not randomised, it was largely hailed as a promising breakthrough.
Randomized trials and routine hospital studies are two types of investigations.
The SOLIDARITY experiment, run by the World Health Organization in numerous countries, and the RECOVERY trial, run in the United Kingdom, were both launched in March to investigate various potential remedies. The US Federal Drug Administration approved the emergency use of hydroxychloroquine in the treatment of COVID-19 on April 27th, pending the findings of a clinical trial, and certain hospitals in the United States and France began to provide hydroxychloroquine to patients on a compassionate basis. Later, the outcomes of these patients who received the medicine were compared to those of patients who did not receive it. Any difference in outcome between those taking and those not taking the drug cannot be attributed fully to the medication if drug allocation is not randomised, hence the data must be read with caution. Differences in outcome, for example, could be due to minor differences in disease severity at the start, advice given to patients on whether or not to take the treatment, or the quality of care they receive during the illness.
Researchers looked at the case reports of all COVID-19 patients who were unwell enough to need oxygen at four large hospitals in France. They compared 84 individuals who were given hydroxychloroquine within 48 hours of being admitted to the hospital versus 89 patients who were not. They found no difference in the rates of deterioration or death between the two groups after correcting for variations in the two groups’ basic characteristics at the start of the trial. [7] A study at a major New York hospital found no difference in the chance of dying or needing to be ventilated between 811 individuals who received hydroxychloroquine and 565 patients who did not. [8]
Is chloroquine a safe medication?
A high dose of chloroquine has been linked to an increased risk of an irregular cardiac rhythm. Chloroquine or hydroxychloroquine was employed in most of the studies above at a dose of 600 mg per day or less, with a doubling dose on the first day. In a randomised experiment of critically ill COVID-19 patients, a research group in Brazil reasoned that unwell patients who do not absorb pills effectively would benefit from a double dose every day, and they compared this high-dose with a low-dose of chloroquine. At one-fifth of the way through the experiment, an interim analysis revealed that patients taking the high dose had a much higher chance of death (39%) than those in the low-dose group (15%), prompting the researchers to terminate the study. [9]
A study published in the Lancet medical journal on May 22, 2020, looked at a commercial database of 96,032 hospitalised COVID-19 patients from 671 hospitals around the world. Patients who received chloroquine or hydroxychloroquine were more likely to die in hospital than those who did not receive these medications, and they were also more likely to have an irregular heart rhythm. [10] The academic community raised major doubts regarding the dataset used in the research’s authenticity, and three of the four authors retracted their manuscript on June 4th because it could not be thoroughly audited.