Hydroxychloroquine: COVID ‘cure’ linked to 17,000 deaths

Used briefly as a COVID treatment, the antimalarial drug hydroxychloroquine might have been fatal for a few patients.

Hydroxychloroquine, an antimalarial drug, was briefly used against COVID-19, but may have been lethal for some patients. | Photo Credit: David J. Phillip/AP Photo/picture-alliance

Amidst the panic of the first wave of COVID-19, existing drugs were repurposed as a treatment. Some ideas were fatal, including one briefly praised by then US President Donald Trump.

Researchers have linked hydroxychloroquine—an antimalarial drug that was briefly promoted by former US President Donald Trump and others as a “miracle” medicine for COVID-19—to an increased mortality rate of up to 11 per cent.

There was a great panic to find treatments for the respiratory disease during the first wave of the pandemic and, as is standard practice, pharmacologists looked at existing medicines to test whether any would help while we waited for a vaccine and the development of new drugs.

Even the WHO looked at hydroxychloroquine as a potential COVID treatment, said former WHO chiefscientist Soumya Swaminathan. “However, [our] trial showed no clinical improvements in patients, so we recommended against its use during the pandemic,” Swaminathan told DW. “At that point, we didn’t observe any association with increased mortality as our sample numbers were relatively small. You need large datasets for such findings to emerge.” She is currently the chairperson of the M.S. Swaminathan Research Foundation.

Scientists: Don’t repurpose drugs in a panic

The researchers writing in the open-access journal Biomedicine & Pharmacotherapy, now say it is possible to link hydroxychloroquine to 17,000 deaths. They warn against repurposing drugs in a panic. “Although our estimates are limited by their imprecision”, they write, “these findings illustrate the hazard of drug repurposing with low-level evidence.”

Swaminathan also emphasised the need for better evidence-based approaches during a pandemic, even amid public fear and panic. Hydroxychloroquine is generally safe, said Swaminathan, but “when you give it to a large number of healthy people preventively, the risk and effects need to be evaluated differently”.

In addition, Swaminathan said, healthcare systems are likely to face new situations like the COVID pandemic in the future, and we need to be prepared for that: “When the need arises, we should be able to put some drugs into rapid human trials without bottlenecks or delays in approvals.”

Hydroxychloroquine, the ‘miracle cure’

“What do you have to lose? Take it,” said Trump, who hailed hydroxychloroquine as a “miracle cure”. And he was not alone. Many world leaders followed suit, sharply increasing the sale of the drug globally. Millions hoarded the drug for personal use. Many countries had recommended that its frontline healthcare workers take it every day as a preventative measure against COVID.

“[It] lowers your immune reaction. This is the reason why it was administered initially in early COVID-19 cases, to suppress the cytokine storm,” said Subarna Goswami, a public health specialistfrom India, where hydroxychloroquine was officially distributed to healthcare workers as a prophylaxis, a treatment to prevent disease.

The reason: COVID was found to produce cytokine storms in patients—their immune systems overreacted to the infection—and that was fatal.

But hydroxychloroquine was not the solution. A somewhat blind hope in the drug came crashing down when the US Food and Drug Administration warned against its use and the WHO discontinued its hydroxychloroquine tests.

How did hydroxychloroquine affect COVID patients?

It is hard to say exactly how hydroxychloroquine affected COVID patients. But small-scale studies, for instance, had patients reporting cardiac discomfort or other side effects in the digestive system.

A lack of larger study groups at the time makes it difficult to pinpoint the precise cause of those effects: researchers say they do not know whether it was the hydroxychloroquine alone, something else, or a combination of factors. “There is every possibility of unforeseen confounding factors that might have contributed to the excess death rate among the [hydroxychloroquine] takers,” said Goswami.

In 2020, an analysis of 96,000 patients initially showed that those treated with hydroxychloroquine were more likely to suffer irregular heart rhythms. The publication of the results in The Lancet halted global trials of hydroxychloroquine for COVID. But the study was then retracted when inconsistencies were found in its data.

This most recent study, the one linking hydroxychloroquine to 17,000 deaths, is a systematic review of studies conducted in the US, France, Belgium, Italy, Spain, and Turkey. Systematic reviews can be more reliable than individual studies because they combine the results from many different studies; so, you get the benefit of more data.

But that also means that data is fused from studies that may have used different or even conflicting methods. If studies were adjusted for the differences in their methodology, they may even yield completely different results, commented Dr Lars Hemkens, whose paper was one among the 44 reviewed for this research. So, there is no consensus yet.

Is hydroxychloroquine still used as a treatment?

Hydroxychloroquine has been used to treat malaria for decades. It works by reducing pain and inflammation. It is usually consumed for a short period of time, until a person is rid of the disease. The drug is also used to treat autoimmune disorders, such as lupus. Its anti-inflammatory properties have been shown to reduce the need for higher doses of other lupus treatments.

Patients typically take a small dose of the drug over a long period, sometimes for the rest of their lives. Most people do not experience side effects, but it sometimes causes stomach pain, digestive problems such as nausea or diarrhoea, dryness of skin, or damage to the eyes after prolonged use.