In the race to find a treatment for COVID-19, two malaria drugs, chloroquine and its derivative hydroxychloroquine, have reared their heads as promising candidates.
Although evidence that these drugs could effectively and safely treat those with COVID-19 is still anecdotal, many health experts and politicians are confident they will work, without causing too many side effects.
Small preliminary studies on the drugs conducted in China and in France have shown mixed, but promising results. And based on the preliminary results, doctors in the United States, Italy, France, China and abroad are already prescribing the drugs to select patients ill with COVID-19.
But before the drugs can be widely administered to COVID-19 patients, more testing is necessary. And for that reason, universities and medical centers around the world have kicked off clinical trials. According to the U.S. National Library of Medicine, there are at least 8 chloroquine and 34 hydroxycloroquine clinical trials that have begun, or will begin shortly.
If testing goes well, these drugs could be made widely available to treat COVID-19 patients at a relatively affordable price.
This is a rapidly evolving story, and this article will be updated as developments occur.
History of the drugs
The story of chloroquine dates back hundreds of years. The drug comes from quinine, the active compound found in the bark of the cinchona tree, commonly located in tropical parts of the Andes in South America. The Incas would use it to treat “shivering,” which was most likely caused by malaria-induced fevers. In the 1600s, Spanish conquerors transported it to Europe.
Chloroquine wasn’t synthesized until 1934, and wasn’t widely used as an FDA-approved malaria drug until after World War II. But the drug has its notable side effects, including depression, blurred vision, nausea and vomiting. And for that reason, a less toxic derivative of the drug, hydroxychloroquine, was developed and approved by the FDA in the mid-1950s.
Both drugs are also currently prescribed for the treatment of lupus and rheumatoid arthritis. They typically come in the shape of a tablet.
The drugs gained public attention again recently when they were proposed as a treatment for COVID-19.
Current battle to treat COVID-19 using chloroquine and hydroxychloroquine
- February 4, 2020 — Chinese researchers find chloroquine could effectively hinder COVID-19
On February 4, a team of Chinese scientists conducted a study showing low micromolar doses of chloroquine could effectively hinder COVID-19 in African green monkey kidney cells.
In the conclusion of their paper, they suggested that chloroquine should be “assessed in human patients suffering from the novel coronavirus disease.” This study got the ball rolling and encouraged medical experts to start considering these malaria drugs as potential treatments for COVID-19.
- February 17, 2020 — Chinese State Council approves chloroquine
Soon after the release of February 4 study, the Chinese State Council announced that chloroquine could be used to treat patients with COVID-19. This initiated a number of clinical trials to test chloroquine in China. Some of the clinical trials haven’t been completed yet, and others have been canceled, as the disease has reportedly begun to wane in China.
- March 3, 2020 — Chinese researchers find hydroxychloroquine was not more effective
Building off of the initial chloroquine study, another Chinese research team decided to research the effectiveness of choloroquine’s derivative, hydroxychloroquine. Through their study, which was conducted between Feb. 6 and Feb. 25 and published on March 3, they determined COVID-19 patients who were treated with hydroxychloroquine didn’t fight off the infection more effectively than any of the patients who weren’t treated with the drug.
But this study had a low sample size of just 30 patients. Out of the 15 patients who were given hydroxychloroquine, 13 recovered within a week. Of the 15 who weren’t given the malaria drug, 14 recovered within a week.
- March 9, 2020 — Separate Chinese research team finds hydroxychloroquine is more effective than chloroquine
A separate Chinese research team also decided to study the effectiveness of hydroxychloroquine. Through their research, they concluded that hydroxychloroquine was, in fact, “more potent than chloroquine” for COVID-19 treatment when tested in monkey cells.
- March 17, 2020 — The University of Minnesota launches clinical trial
On March 17, researchers from the University of Minnesota launched an initial clinical trial to ultimately determine the effectiveness of hydroxychloroquine in treating COVID-19. In an effort to make the trial as conclusive as possible, the researchers are recruiting up to 1,500 participants who have recently been exposed to the virus.
- March 18, 2020 — WHO announces SOLIDARITY trial
With some anecdotal evidence that chloroquine and hydroxychloroquine could be used to treat COVID-19 patients, the World Health Organization decided to test the drugs’ effectiveness as part of its SOLIDARITY initiative. In essence, SOLIDARITY is an internationally coordinated effort to, once and for all, find which existing drug could most effectively treat COVID-19. Thousands of patients in dozens of countries are expected to partake in clinical trials.
- March 20, 2020 — French researchers find hydroxychloroquine is most effective when used with antibiotic azithromycin
Building off the studies conducted in China, a team of French researchers led by microbiologist Didier Raoult, who heads the infectious diseases department of La Timone hospital in Marseille, released a preliminary study of their own suggesting that hydroxychloroquine is most effective against COVID-19 when used in combination with the antibiotic azithromycin, more commonly known as Z-PAC.
The promising results presented in the French study immediately caught the attention of politicians, including President Trump, who said the drug cocktail has a chance to be one of the “biggest game changers in the history of medicine.”
However, the study was met with criticism from the medical community.
The study was not peer-reviewed prior to publication, and it only involved a treatment group of about 20 infected patients. The researchers started with 26 infected patients, but six of them dropped out. Of those who dropped out, three of them were sent to intensive care and one of them died. Additionally, the researchers were only swabbing for COVID-19 in patients’ throats and nasal cavities, so the virus could still have existed in the body, perhaps in the lungs.
The study also sparked concern regarding the safety of using the two drugs together.
“This is a DANGEROUS combination of drugs with tons of side effects. Together they can make your heart go into abnormal rhythms and even KILL you. Please do NOT take them unless they have been prescribed by your doctor,” Sam Ghli, a physician in Lexington, Kentucky, tweeted.
Raoult more recently published a second “observational” study that reinforced his prior conclusion. This time, the study involved a larger treatment group of 80 patients.
But this study has also seen a fair share of criticism, largely because it doesn’t include a control group.
- March 22, 2020 — New York receives malaria drugs from the FDA to implement drug trials
On March 22, the FDA solidified a plan to send 750,000 doses of chloroquine and 70,000 doses of hydroxychloroquine to New York hospitals so they can be administered to sick patients.
“The president is optimistic about these drugs and we are all optimistic that it could work,” New York Governor Andrew Cuomo said in a press conference. “I’ve spoken with a number of health officials and there is a good basis to believe that they could work. Some health officials point to Africa, which has a very low infection rate and there’s a theory that because they’re taking these anti-malaria drugs in Africa, it may actually be one of the reasons why the infection rate is low in Africa. We don’t know, but let’s find out and let’s find out quickly. And I agree with the president on that.”
- March 24, 2020 — Supply shortage of chloroquine and hydroxychloroquine peaks
As word spread that chloroquine and hydroxychloroquine could be used to treat COVID-19, demand for hydroxychloroquine, in particular, has skyrocketed, resulting in an uptick in prescriptions ordered. On March 24, the American Society of Hospital Pharmacists officially announced a supply shortage.
The shortage is dangerous because it leaves those currently prescribed the drug to treat their lupus or arthritis unable to fill their prescriptions.
In addition to the increase in consumer demand, there has also been a report that doctors have been hoarding the drugs for themselves, their families and colleagues. The report also suggested that some hospitals and pharmacies have been buying the drugs in bulk to prepare.
Other individuals have started using the drugs, and non-pharmaceutical versions of them, to self-medicate, which can be extremely dangerous.
An Arizona man died and his wife became critically ill after they both decided to ingest fish food that contained chloroquine phosphate. They were “afraid of getting sick,” the wife told NBC. The Center For Disease Control (CDC) has since issued statements warning people not to self-medicate with these drugs or non-pharmaceutical versions of them.
And in an effort to keep people from hoarding the drugs, the US Department of Health and Human Services listed hydroxychloroquine as a protected medical resource, following an executive order from President Trump. This measure is intended to prevent hoarding and price gouging.
- March 29, 2020 — FDA issues an emergency use authorization (EUA) for hydroxychloroquine and chloroquine
On March 29, the FDA issued an EUA for hydroxychloroquine and chloroquine so that they can be used widely throughout the United States in treating patients hospitalized with COVID-19 and for clinical trials.
It encouraged pharmaceutical companies to donate the drugs to the Strategic National Stockpile so that they can be “distributed and prescribed by doctors to hospitalized teen and adult patients with COVID-19, as appropriate, when a clinical trial is not available or feasible.”
In conjunction with the EUA, the U.S. Department of Health and Human Services has already accepted 30 million doses of hydroxychloroquine donated by Sandoz and 1 million doses of chloroquine phosphate donated by Bayer Pharmaceuticals.
And Rising Pharmaceuticals has vowed to donate 1 million hydroxychloroquine sulfate tablets in March and April. Teva plans to donate more than 10 million hydroxychloroquine sulfate tablets within the next month. And Sandoz intends on donating more than 100 million, in addition to the 30 million it has already donated.
Although the FDA is acting in an effort to administer treatments as quickly as possible, some medical experts are concerned by how fast things are moving.
“I would like to see who at FDA’s (Medical Countermeasures Initiative) signed off on this EUA despite the total lack of scientific evidence that chloroquine/hydroxychloroquine are beneficial in the treatment of COVID-19,” tweeted Luciana Borio, who formerly served as FDA’s acting chief scientist. “EUA is supposed to be issued when the evidence indicates that benefits outweigh the risks.”
- March 30, 2020 — University of Washington & NYU announce joint clinical trial
On March 30, the University of Washington and New York University announced they jointly would be conducting a six-site, 2,000-person clinical trial to conclusively test whether hydroxychloroquine could be used to treat COVID-19 patients.
“Currently, there is no proven way to prevent COVID-19 after being exposed,” Anna Bershteyn, assistant professor of population health at NYU and co-principal investigator on the study, said in a news release. “If hydroxychloroquine provides protection, then it could be an essential tool for fighting this pandemic. If it doesn’t, then people should avoid unnecessary risks from taking the drug.”
They are not the only U.S. universities looking for an answer. Columbia University will also be running clinical trials to test the effectiveness of hydroxychloroquine in treating COVID-19.
Ongoing research
There is much optimism surrounding the possibility that chloroquine and/or hydroxychloroquine could be effective treatments for COVID-19 and be widely administered to patients.
And medical experts are working as fast as they can to reach a conclusion. But until they do, which will likely take weeks or even months, evidence suggesting either or both of these two malaria drugs could serve as an effective and safe COVID-19 treatment remains purely anecdotal.
