Antimalarial Medications: A COVID-19 Treatment Option?

By | March 30, 2020

The outbreak of the most recent iteration of coronavirus — COVID-19 — has experts scrambling to find effective methods of delivering supportive care and minimizing the effect of the illness. As Dr. Roger Seheult, co-founder of MedCram.com, explains in this short video, several factors have been responsible for the rapid spread.

One of the drugs currently under investigation is chloroquine, a treatment commonly used to keep malaria in check. Chloroquine is a synthetic derivative of quinine, which was once the only treatment for malaria. However, quinine is bitter and has significant side effects.1

Legend has it that to make it easier to drink, the British living in India mixed it with gin and lemon or lime.2 The British colonials grew to enjoy the taste, and soon afterward tonic water was granted a patent in 1858. Schweppes introduced tonic water in the U.S. nearly 100 years later and the gin and tonic has remained an integral part of British and American history.

However, while tonic water is flavored with quinine, it doesn’t contain nearly as much as the medicine. Tonic water contains no more than 83 milligrams per 1-liter bottle (33.8 ounces), but the therapeutic dose of quinine is 500 mg to 1,000 mg.3

In remarks in a press briefing,4 President Trump said the U.S. Food and Drug Administration had approved use of the malaria drug chloroquine — which is not the same as quinine — to treat coronavirus. However, on the same day the FDA5 released a statement saying they were only “investigating” the drug “to determine whether it can be used to treat patients with mild-to-moderate COVID-19.”

“Studies are underway to determine the efficacy in using chloroquine to treat COVID-19,” the statement continued, with FDA Commissioner Dr. Stephen Hahn adding:

“At the same time, we will engage with domestic manufacturers to ramp up production of this product to mitigate any potential supply chain pressures. If clinical data suggests this product may be promising in treating COVID-19, we know there will be increased demand for it. We will take all steps to ensure chloroquine remains available for patients who take it to treat severe and life-threatening illnesses such as lupus.”

However, as one blogger website pointed out, “MDs can prescribe chloroquine and hydroxychloroquine for Covid 19 right now. The FDA doesn’t and can’t regulate off-label prescriptions.”6 And, apparently, many doctors not only know that, but are taking advantage of that loophole, according to The New York Times:7

“None of the drugs have been approved by the U.S. Food and Drug Administration for that use. Some of them — including chloroquine and hydroxychloroquine — are commonly used to treat malaria, lupus, rheumatoid arthritis and other conditions …

‘I have multiple prescribers calling in prescriptions for Plaquenil for themselves and their family members as a precaution. Is this ethical?’ one person wrote on Sunday in a Facebook group for pharmacists, referring to a brand name of hydroxychloroquine.”

Pharmacists Urge: ‘Put the Brakes on’ Hoarding

Out of concern that doctors not only might be jumping the gun on whether the malaria drugs actually work for COVID-19, but also are denying patients who actually need it for chronic conditions like lupus and arthritis, state pharmacy boards are urging their members to restrict prescriptions for the drugs. Besides, these drugs also can have serious side effects, NPR notes:8

“Our members are definitely seeing more demand for this medication and possibly some people trying to hoard the medication,” says Todd Brown, executive director of the Massachusetts Independent Pharmacists Association … Pharmacists are seeing an increase in requests and prescriptions for them in instances where it’s not clear why the patient needs it at this time’ …

Brown is suggesting that pharmacists restrict prescription quantities and fill prescriptions only for patients with an active need for hydroxychloroquine … Michael Barnett, a primary care physician and assistant professor at the Harvard T.H. Chan School of Public Health, says that even if the drug turns out, from the clinical studies now in progress, to be effective against COVID-19, it must be saved for those most in need.

Barnett is sympathetic [to those who want to try everything they can to cure COVID-19], but he points out that this powerful medicine has serious side effects, so it should not be taken unless there’s a known benefit.”

On a bizarre side note, another consumer warning made headlines after a husband and wife in their 60s decided to self-medicate with an aquarium cleaner that has a different form of chloroquine in it. Both were hospitalized within 30 minutes of ingesting the toxic substance, The Sacramento Bee reported;9 the husband later died.

The fish tank cleaner “has the same active ingredient as the drug chloroquine phosphate, which is used to treat malaria, but is formulated differently,” the medical director from a local poison control center explained. Unfortunately, at least three others made the same mistake in Nigeria, so it’s important to remember that you should not take any drug without your physician’s express direction.

Past Data Suggest Chloroquine Studies May Be Fruitful

Historically, there is strong evidence that chloroquine and hydroxychloroquine are effective in the lab against the SARS coronavirus that appeared in 2003.10,11,12 Laboratory testing also reveals chloroquine is effective in cell cultures against COVID-19 when combined with an antiviral drug, remdesivir.13 Hydroxychloroquine (Plaquenil) uses the same pathway as chloroquine, but with a safer side effect profile.14

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These and other results have prompted scientists to call for further research into the use of the antimalarial drugs to stem the tide of COVID-19 infection.15 Recently, results of a very small clinical trial using Plaquenil alone for the infection have been announced in China, but access to the data was not initially released to other scientists for review,16 and then when it was the data showed very little difference between the drug and the control group.17

Similar studies have been ongoing for several years. For example, in 2009,18 one study evaluated the use of chloroquine in human coronavirus subtype OC43, known to cause severe lower lung infections.19 The researchers used an animal model and found pretreatment demonstrated the drug was highly effective against this subtype. Interest in antimalarial drugs highlights a unique distribution of the virus.

As noted in a preliminary paper currently undergoing peer-review, “Global Spread of Coronavirus Disease 2019 and Malaria: An Epidemiological Paradox”:20

“From the analysis of distribution data, the endemic presence of malaria seems to protect some populations from COVID-19 outbreak, particularly in the least developed countries. Of note, the mechanism of action of some antimalarial drugs (e.g. antiviral function) suggests their potential role in the chemoprophylaxis of the epidemic.”

Malaria is caused by a parasite passed to humans by infected Anopheles mosquitoes. The World Health Organization’s African region21 experiences a large proportion of the burden, with 93% of all cases worldwide and 94% of deaths related to malaria.

When you consult the Johns Hopkins Medicine’s22 user-friendly, interactive map to track the outbreak worldwide, it’s apparent the only other large land mass with fewer cases than Africa is Russia23 — which is indeed intriguing, if nothing else.

Experts Are Testing Efficacy of Chloroquine Against COVID-19

In light of past results and current data, one clinical trial24 underway is enrolling 1,000 workers who have a higher potential to become infected based on their exposure. The University of Oxford is beginning the trial in May 2020 and anticipates closing it in May 2022.

The researchers are using a double-blind, randomized, placebo-controlled study design to evaluate the use of chloroquine versus a placebo taken over three months or until they are diagnosed with COVID-19. The researchers are measuring the severity of respiratory illness and clinical outcomes.

One recently released study had encouraging results using hydroxychloroquine.25 Infection control specialist Dr. Didier Raoult from France enrolled 24 patients who had confirmed COVID-19. The patients received 600 mg of hydroxychloroquine each day and their viral load was monitored in a hospital setting.

Depending upon the clinical presentation, researchers added azithromycin to the treatment protocol. Patients from another hospital who refused the protocol were used as a negative control. The scientists concluded that despite the small sample size, the survey “shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.”

Another physician shared his positive results using a similar protocol with a small group of patients.26 Dr. Vladimir Zelenko treats a close knit Jewish population of 35,000 in Kiryas Joel, Monroe, New York. Zelenko posted a video of himself addressing Trump about the treatment he’d developed, and asked Trump to use it nationwide.

He told radio host Sean Hannity that he’d had 100% success rate with patients by using hydroxychloroquine, azithromycin and zinc sulfate for five days. “I’ve seen remarkable results; it really prevents progression of disease, and patients get better,” he said.

In response, county health officials said it was “unsubstantiated” and “highly irresponsible” for Zelenko to apply his patients’ outcomes to the entire community, and urged residents to listen to public health officials and continue with recommended social distancing and other prevention methods.27

The Protocol Is Not Without Risk

Chloroquine raises the pH of vesicles in the cells that are hijacked by the virus. The normally slightly acidic environment facilitates the viral infection. Jeremy Rossman at the University of Kent expects positive lab results, but notes28 “there’s often a huge gap between how it works in the lab cells and how it works in the body.” One gap includes the potentially deadly side effects.

While results are hopeful, it is important to note, as Seheult points out, both drugs have the side effect of elongating your QT wave in an electrocardiogram. This means the electrical activity in the heart is altered. The most common symptoms of the condition are seizure, fainting and sudden death.29

These side effects are not minimal. Just two days after China issued a treatment guideline to use chloroquine, it sent a warning to closely monitor adverse side effects and limit use to those without heart, liver or kidney disease and those who are not taking antibiotics such as azithromycin or prescribed steroids.30

Malaria and COVID-19 Don’t Have Much in Common — Or Do They?

Although malaria and coronavirus don’t appear to have much in common, the drug is effective against malaria and may reduce the symptoms of coronavirus. Seheult explains a potential mechanism:31

“When the coronavirus infects your cell it’s going to dump into your cell a messenger RNA that’s going to be translated using ribosomes. Those ribosomes, the first thing they are going to do is translate that RNA molecule into a protein called RNA dependent RNA polymerase, or replicase. And, it is this enzyme that is … inhibited by high intracellular concentrations of zinc.

Well, as it turns out, chloroquine is a zinc ionophore, as is hydroxychloroquine. Zinc ionophore is just basically a protein or a gate that allows zinc to come into the cells. We don’t know if that is the actual way it is working in this case, but it does seem to lend credence to the mechanism of action that zinc does inhibit replicase and that hydroxychloroquine and chloroquine increase the intracellular concentration of zinc.”

Evidence shows zinc gluconate and zinc acetate effectively reduce the severity and duration of viral infections. Zinc is crucial to the effectiveness of your immune system, enzyme function, protein synthesis and cell division. Studies demonstrate using zinc lozenges reduces the duration of a cold by 33% and lessens the severity of your symptoms.32

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Zinc is a necessary component of zinc finger antiviral proteins shown to33 “inhibit the replication of certain viruses by repressing the translation and promoting the degradation of the viral mRNAs.” This activity demonstrates a similar inhibition against influenza A virus.34

However, not all zinc products yield the same results. When the lozenge contains more than zinc, it may interfere with the process. Multiple ingredients have a way of interacting with each other, even when they are safe and effective when used on their own.

For instance, there is evidence citric acid, mannitol and sorbitol bind with zinc and reduce your absorption. For more on how to use zinc during a cold or flu see “When Should You Take Zinc to Shorten Your Cold?

Short-Term Cost May Yield Long-Term Benefits

Currently embroiled in litigation35,36 over the manufacture and distribution of their herbicide Roundup, Bayer announced it would donate 3 million tablets of chloroquine phosphate (Resochin), a drug the company discovered in 1934.37

Resochin is used for malaria prevention and treatment in Europe38 but hasn’t been approved for use by the FDA. This donation to the medical effort to diminish the effects of COVID-19 may offer Bayer a path to drug approval in the U.S.

However, while the offer has garnered media attention and the company may hope it softens public opinion, the drug is chloroquine-based, as opposed to the current FDA approved drug Plaquenil,39 which uses the better tolerated hydroxychloroquine.

Rapid Spread of COVID-19 Raises Need for Preventive Measures

In the featured video, Seheult describes the results of a study published in Science in March 2020.40 The researchers used a mathematical model to determine how the disease spread before and after the travel ban in China went into effect January 23, 2020.

They found 86% of people were undiagnosed on that date, which means they didn’t get tested for the virus, so they didn’t know they had it. The authors of the study point out that those who are undiagnosed often have mild or no symptoms of a viral infection and thus are unaware of the need to be tested.

The mathematical model used in the study revealed these undocumented cases were responsible for 79% of all documented cases in China. This meant if the undocumented cases of COVID-19 had been identified, the number of known infections would have dropped by 79%, and as Seheult describes, the number infected in Wuhan would have dropped by 66%.

According to the researchers, those who were undiagnosed, with mild to no symptoms, were 55% as contagious as those with symptoms. However, the sheer number of undiagnosed cases contributed to the rapid spread of the virus through China. The researchers wrote:41

“Our findings also indicate that a radical increase in the identification and isolation of currently undocumented infections would be needed to fully control SARS-CoV2. Increased news coverage and awareness of the virus in the general population have already likely prompted increased rates of seeking medical care for respiratory symptoms.”

As the researchers point out, it takes a combination of identification using thorough testing strategies and subsequent isolation of those who have the virus to fully contain and control the spread.

However, while public knowledge of the first cases in China occurred on December 31, 2019,42 it wasn’t until February 3, 2020, that the U.S. Centers for Disease Control and Prevention43 announced the development of a laboratory test kit available in the U.S.

US Declines Use of WHO Test Kit Available in January

Once the genetic sequence was available for COVID-19 in January, German researchers quickly developed a PCR test for the virus. The New York Times44 reported the initial test kits developed by the CDC were flawed and testing snafus were the result of policy makers, not science. The Verge reported:45

“That test became the basis for the World Health Organization’s (WHO) test used in countries around the world, including South Korea, but which the Centers for Disease Control and Prevention (CDC) declined to use.

PCR tests are, in theory, fairly simple to create: scientists pick snippets of the virus’s gene and use a series of chemicals to look for that gene snippet in the sample. If they find the snippet, it means the patient has the virus.”

South Korea is one country that took rapid action on two fronts. As Seheult mentions at the end of the video, the country began using the antimalarial drug early. Data collected by Johns Hopkins Medicine46 show that while South Korea is in the top 10 countries with the virus, the number who have died are near the numbers commonly attributed to flu — 1.16% as of March 22, 2020.

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As Science Magazine reports,47 all of this has been accomplished without massive citywide lockdowns. Instead, the country instituted necessary populationwide testing with extensive efforts to trace contacts so those carrying the virus or who had been exposed were quarantined to isolate the virus.

In all, by March 17, 2020, South Korea had “tested more than 270,000 people, which amounts to more than 5,200 tests per million inhabitants … The United States [had] so far carried out 74 tests per 1 million inhabitants, data from the U.S. Centers for Disease Control and Prevention show.”48

Politics, Not Science May Have Slowed Testing

In Italy the spread of the virus had different results. The reports of illness and death have shocked the world, driving fear that the same infection rate and mortality will spread worldwide. However, it’s important to note that situations between countries differ. Where South Korea began volume testing to isolate asymptomatic people and treatment in January, Italy struggled with political arguments.49

One Italian town undertook populationwide testing and has reportedly been able to contain the outbreak in their town. These results underscore the recommendations of researchers to identify and isolate those infected. A professor of clinical immunology at the University of Florence commented in a letter to authorities:50

“The percentage of infected people, even if asymptomatic, in the population is very high. The isolation of asymptomatics is essential to be able to control the spread of the virus and the severity of the disease.”

The second part of the equation in Italy is related to the higher rate of death than most other countries. This increased rate has also been identified during flu season,51 as Italy’s mortality attributed to the flu is higher than other European countries, especially in the senior population.

Wired52 reveals 23% of the Italian population are seniors, as compared to 16% in the U.S. Italian young people also tend to maintain close relationships with the elderly, increasing the risk that an asymptomatic young person could spread the virus to a senior. The scientists involved in the recent research evaluating the spread of the virus concluded:53

“The 2009 H1N1 pandemic influenza virus also caused many mild cases, quickly spread globally, and eventually became endemic. Presently, there are four, endemic, coronavirus strains currently circulating in human populations (229E, HKU1, NL63, OC43). If the novel coronavirus follows the pattern of 2009 H1N1 pandemic influenza, it will also spread globally and become a fifth endemic coronavirus within the human population.”

Helpful Nutrient Options for Viral Prevention and Treatment

As this story unfolds, I am committed to bringing you viable prevention and treatment options you can use at home. A recently published article54 by Mark McCarty and James DiNicolantonio, PharmD, proposes there are nutraceuticals that may help reduce symptoms and severity of influenza and coronaviruses.55 According to the authors, these viruses:

“… cause an inflammatory storm in the lungs and it is this inflammatory storm that leads to acute respiratory distress, organ failure, and death. Certain nutraceuticals may help to reduce the inflammation in the lungs from RNA viruses and others may also help boost type 1 interferon response to these viruses, which is the body’s primary way to help create antiviral antibodies to fight off viral infections.”

From the conclusions of several randomized clinical studies, DiNicolantonio and McCarty believe the antiviral effects of some nutraceuticals are quite clear, and hope these benefits will encourage further research to test this strategy.

You’ll discover how some cost-effective supplements may reduce the severity and duration of your symptoms of colds, flu or COVID-19 in “Quercetin and Vitamin D — Allies Against Coronavirus?

It’s also important to remember to care for your gut microbiome, reduce your sugar and carbohydrate intake, get quality sleep and practice good hand-washing to support your efforts to stay well.

Remember to stay away from others when you are sick to avoid spreading any virus you may be carrying, and to seek medical attention as you would if you were sick with a bad flu. Difficulty breathing is a clear indicator that medical attention may be required. This is particularly true if you are pregnant, have a weakened immune system or a chronic medical condition that may place you in a higher risk category for severe COVID-19 infection.56


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