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Could Antimalarial Drugs Really Help Treat COVID-19?

Could Antimalarial Drugs Really Help Treat COVID-19?

There is some early evidence they could be effective in managing novel coronavirus infections.

Updated on March 23, 2020 at 4:45pm EST.

As scientists around the world scramble to develop a vaccine to protect against COVID-19 and antiviral medication to help manage the infection, an 85-year-old malaria drug, called chloroquine, and its less toxic derivative, known as hydroxychloroquine, have emerged as potential weapons doctors on the front lines could use to fight the novel coronavirus.

During a press conference on Thursday, March 20, President Trump announced that chloroquine and hydroxychloroquine are among an array of existing medications under consideration by the U.S. Food and Drug Administration (FDA) for the prevention or treatment of COVID-19.

“This is prescribed for many years for people to combat malaria, which was a big problem and it’s very effective,” Trump said. “I sure as hell think we ought to give it a try.”

Though promising, the assertion that these antimalarial drugs could help protect against or manage COVID-19 is currently based on limited evidence, cautions director of the National Institute of Allergy and Infectious Diseases, Anthony Fauci, MD, who is also a member of the White House Coronavirus Task Force.

“We’re trying to strike a balance between making something with a potential of an effect to the American people available, at the same time that we do it under the auspices of a protocol that would give us information to determine if it’s truly safe and truly effective,” Dr. Fauci said during a March 21 White House briefing.

What researchers have found
Scientists in France, led by Didier Raoult, MD, PhD, conducted a small, preliminary study, which was published on March 20 in the International Journal of Antimicrobial Agents, involving 36 patients hospitalized with COVID-19. Of these people, 14 received hydroxychloroquine, six received hydroxychloroquine and the antibiotic azithromycin, while the remaining 16 patients received traditional supportive care.

Five days after treatment, 13 of the patients, or 65 percent of those who took only hydroxychloroquine were negative for the virus. All six of the patients who received the dual treatment had cleared the virus, suggesting that when combined with azithromycin, the benefits of hydroxychloroquine are even greater. The researchers noted that just three of the 16 control patients who received standard supportive care were no longer infected.

Azithromycin is used to cover the possibility of a second infection, or superinfection, but the drug could also have some antiviral effects as well, the researchers pointed out. 

“Our preliminary results also suggest a synergistic effect of the combination of hydroxychloroquine and azithromycin,” the study’s authors wrote, noting that azithromycin has been shown to be active in lab tests against Zika and Ebola viruses and to help prevent severe respiratory tract infections among patients with viral infections. The researchers noted, however, that more investigation into the effectiveness of the drug combination is needed, particularly among severe cases of COVID-19. 

The Centers for Disease Control and Prevention (CDC) noted that hydroxychloroquine and the combined hydroxychloroquine-azithromycin therapy reduced detection of COVID-19 compared to the control group, but the study did not assess the clinical benefit of these treatments, or how they affected patients’ symptoms, wellbeing and overall outcomes.

Aside from its small sample size, this French study has other limitations, including limited long-term outcome follow-up.

Their findings, however, are supported by Chinese researchers who used lab tests to show that hydroxychloroquine may help prevent the novel coronavirus from entering cells.

Based on this limited evidence, chloroquine or hydroxychloroquine are currently being used to treat hospitalized COVID-19 patients on an uncontrolled basis in several countries, including the United States, the CDC reports.

The fact that hydroxychloroquine (brand name, Plaquenil), is an off-the-shelf drug is another potential win. The drug has already been tested and FDA-approved for use against malaria and to treat certain inflammatory conditions. Not only do doctors understand the drug well, but there is a relatively cheap, generic version available.

The possible downsides
The FDA and CDC point out that larger clinical trials are needed to assess how effective the drug is against the novel coronavirus. In the U.S., several clinical trials of hydroxychloroquine for the prevention or treatment of COVID-19 infection are planned or will be enrolling soon. A study focused on treatment following exposure to the coronavirus, involving 1,500 people, is already underway at the University of Minnesota.

While there are no FDA-approved drugs to treat, cure or prevent COVID-19, the FDA acknowledges that there are several existing drugs approved for other conditions that could help ease novel coronavirus symptoms. “We understand and recognize the urgency with which we are all seeking prevention and treatment options for COVID-19,” said FDA Commissioner Stephen Hahn, MD in a March 19 statement.

Dr. Hahn added, however, that it’s critical to ensure that these drugs are truly effective against the novel coronavirus, “otherwise we risk treating patients with a product that might not work when they could have pursued other, more appropriate, treatments.”

Hydroxychloroquine can also have side effects like headaches, nausea, vomiting and diarrhea. Rarely, suicidal behavior may also be associated with this medication. Hydroxychloroquine could lead to an irregular heart rhythm, called QT prolongation, among patients with chronic conditions, including kidney disease. It may also interact with some other medications.

Meanwhile, patients who are already prescribed hydroxychloroquine for the treatment of lupus, rheumatoid arthritis (RA) and Sjogren's syndrome may face shortages of their medication if stockpiles of the drug are diverted to help fight the pandemic.

Prevention is still the best protection
Currently, the most effective way to help curb the spread of COVID-19 is to avoid exposure to the coronavirus.

Washing your hands often and thoroughly with soap and water for at least 20 seconds is one of the most effective ways to protect yourself. If you don’t have access to soap and water, using an alcohol-based hand sanitizer is a good alternative—if you pick the right one and use it frequently and properly.

Be sure that your hands are clean before eating or touching your eyes, mouth or nose, after using the bathroom and while working in the kitchen.

Other precautions include social distancing, avoiding groups or gathering and staying at least six feet away from others, covering your coughs or sneezes and disinfecting commonly used objects and surfaces you come into contact with throughout your day.

Medically reviewed in March 2020.

Sources:
The White House. “Remarks by President Trump, Vice President Pence, and Members of the Coronavirus Task Force in Press Briefing.” March 20, 2020.
The White House. “Remarks by President Trump, Vice President Pence, and Members of the Coronavirus Task Force in Press Briefing.” March 19, 2020.
Philippe Gautreta, Jean-Christophe Lagiera, Philippe Parolaa. “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial,” International Journal of Antimicrobial Agents. March 2020.
J. Liu, R. Cao, M. Xu et al. “Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro.” Cell Discovery. 6, 16 (2020).
Centers for Disease Control and Prevention. “Information for Clinicians on Therapeutic Options for COVID-19 Patients.”
University of Minnesota. “COVID-19 clinical trial launches.”
U.S. Food and Drug Administration. “Coronavirus (COVID-19) Update: FDA Continues to Facilitate Development of Treatments.”
Centers for Disease Control and Prevention. “Medicines for the Prevention of Malaria While Traveling Hydroxychloroquine (Plaquenil).”
Arthritis Foundation. “Hydroxychloroquine (Plaquenil) Shortage Causing Concern.”

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