One of the most fervent supporters of Chloroquine and hydroxychloroquine has been the President of the United States. President Trump has touted the drug as being a “game-changer” and his overwhelming support of its use in COVID-19 as a successful treatment has caused the US to import the drug in high quantities.

Unfortunately, Chloroquine is not panning out to be the saving grace President Trump has promised; creating disappointment within the White House staff and the COVID response team.

Chloroquine came onto the scene as a potential MERS treatment back in 2012, but was not investigated further because it didn’t show enough activity against the virus. There are also risk factors with the drug and the usage can cause problems independent of the COVID infection. The American Health Association has cautioned the US Government that “The antimalarial medication hydroxychloroquine and the antibiotic azithromycin are currently gaining attention as potential treatments for COVID-19, and each have potential serious implications for people with existing cardiovascular disease,” (AMA statement. )

Recently, small studies have picked up chloroquine again, looking into whether the drug could block coronaviruses such as COVID-19 from infecting cells. Keeping in mind that the drug would be the last resort, could it be a potential drug for COVID-19 patients who are not responding to other treatments. The antimalarial is known to cause dangerous side-effects; even its relatively ‘safer’ cousin, hydroxychloroquine, doesn’t have a great track record. Of particular concern is the risk for patients to develop serious heart problems.

The latest research to add to these worries is a clinical trial from Brazil. The team released their preliminary results on the pre-print server medRxiv when they stopped the high-dose arm of their study after just six days, as several patients died – especially in the group randomized to receive higher doses of the drug.

“Complications include severe electrical irregularities in the heart such as arrythmia (irregular heartbeat), polymorphic ventricular tachycardia (including Torsade de Pointes) and long QT syndrome, and increased risk of sudden death.”

Preliminary findings suggest that the higher chloroquine dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards and high lethality rate.

The researchers noted that they experienced even more deaths in the high-dose group than were documented on day six. And it doesn’t mean the low-dose group is safe, either.

“The major difference between the high-dose and the low-dose group occurred during the first three days and the actual toxicity – two patients in the high-dose chloroquine arm developed ventricular tachycardia before death,” Vanderbilt University infectious disease researcher William Schaffner.

When looking at the raw data, it becomes clear that the high-dose group was more toxic, but it’s not as though the low-dose group was without concern.

These worrying results come after a hospital in France also stopped a trial of hydroxychloroquine due to side effects and risk of heart damage, and similar small studies have found little difference in COVID-19 patients treated with a combination of the malarial drug and the antibiotic; the latter carries a risk of heart rhythm side-effects even by itself.

The research team in Brazil moved all of the remaining patients to the low-dose arm of the trial in compliance with a recommendation from the Data Safety and Monitoring Board. Additionally, they recommend more trials to evaluate the role chloroquine might play in COVID-19 treatment and prophylaxis – much-needed data that could benefit us all in the future.

“Even if we fail to generate good evidence in time to control the current pandemic, the information will highly impact the way we deal with next coronavirus outbreaks in the future,” the team writes. The research is available on medRxiv.

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