COVID-19. Is Chloroquine the Answer?

The first stories on the successful treatment of COVID-19 began to come out of South Korea who reported an extremely low death rate from the virus. When that country reported its numbers – just 120 dead out of 9037 confirmed cases, a death rate of just 1.3% compared to 9.5% in Italy, the factor in accomplishing this appeared to be the use of the anti-malarial drug chloroquine.

Other countries, including China and Belgium, have added chloroquine to their treatment guidelines even though it is not approved for this purpose. Other medical providers have gone one step further and stated that chloroquine, combined with azithromycin, is the “magic bullet” when it comes to this virus. Today, many American doctors are looking towards these outcomes and are convinced that this combination, can successfully treat COVID-19. So is it true? And just what are chloroquine and azithromycin?

Chloroquine, also known as chloroquine phosphate along with hydroxychloroquine are drugs normally used to prevent or treat malaria caused by mosquito bites in countries where the disease is most prevalent. Both are oral prescription medications that have been used for the treatment of malaria and certain inflammatory conditions since the mid-twentieth century.

Chloroquine has been used for malaria treatment and chemoprophylaxis (preventing disease) -- but also is used for the cleaning of aquarium fish tanks. Hydroxychloroquine is used for the treatment of rheumatoid arthritis, systemic lupus erythematosus, and porphyria cutanea trade (a blood disorder that affects the skin and is sometimes called "vampire disease" because symptoms are after exposure to sunlight), according to the Centers for Disease Control and Prevention (CDC).

Chloroquine has been used to treat malaria since the 1940s. Hydroxychloroquine, sold generically and under the brand name, Plaquenil came along a decade later and has fewer side effects.

The use of chloroquine to treat viral infections came to light after French researchers published an article in the International Journal of Antimicrobial Agents describing the potential use of a combination of hydroxychloroquine and the antibiotic azithromycin, which is better known as Z-Pak.

Azithromycin is a widely-used antibiotic for bacterial infections. Side effects include upset stomach, diarrhea, nausea, vomiting or abdominal pain. Less common but serious side effects include hearing damage or deafness, drooping eyelids and blurred vision, difficulty swallowing or speaking, muscle weakness, and liver damage. It is contraindicated for people allergic to azithromycin and other antibiotics, including erythromycin, clarithromycin, telithromycin. It is also contraindicated in people with liver and kidney disease.

The French study, which is small by study standards, “showed a significant reduction of the viral carriage” after six days of treatment and “much lower average carrying duration” compared to patients receiving other treatment. Six patients in the trial were asymptomatic and 22 had upper respiratory tract infection symptoms. Eight patients had lower respiratory tract infections. Twenty cases were treated in the study, with untreated patients acting as negative controls.

But scientists warn that beliefs on a possible cure have not come from large, carefully controlled studies that would provide proof of the treatment's efficacy. Many doctors are also wary of raising false hope by backing a drug protocol that could still pose health risks to the worldwide community with the "cure being worse than the virus" itself.

So how does chloroquine work?

Recent in vitro studies (done in a petri dish rather than with animals or humans), have shown that both hydroxychloroquine and chloroquine exhibited anti-viral properties against SARS-Cov-2, the virus that causes COVID-19.

According to researchers, these two medications can raise the pH level in the portion of the cell where viruses enter (viruses appear to like a more acidic environment). The elevated level prevents fusion and keeps the virus at bay. It also appears that chloroquine increases zinc concentrations at the cellular level which interrupts the phasing of the virus. Zinc is known to maintain robust immune responses within a cell.

Another action that chloroquine may be responsible for is blocking enzymes that are involved in the fusion between the virus and cells in the lungs, effectively limiting the replication of SARS-Cov-2. But again, researchers say larger studies are needed.

The safety of chloroquine

Before we view this medication as a wonder drug and begin dispensing it on a large scale basis, the fact is that both chloroquine and hydroxychloroquine are not without their problems. Meghan May, a microbiologist at the University of New England College of Osteopathic Medicine, cited her concerns, "Chloroquine is an extremely toxic drug with a terrible side effect profile. Hydroxychloroquine is far safer, but its side effects are still significant if it is not abundantly clear that it is beneficial, giving this drug to a critically ill patient feels risky."

And just what are those risks? The drugs can cause heart rhythm problems, severely low blood pressure, low blood sugar, a worsening of psoriasis, as well as muscle or nerve damage. Of greatest concern with these drugs are reports of the failure to fully appreciate that they are known to have a risk of Torsades de Pointes, a specific type of abnormal heart rhythm that can lead to sudden cardiac death. This obviously has huge implications for those who are most at risk of death from COVID-19 - the elderly with underlying health conditions. Many have problems with arrhythmias and still more have undiagnosed cardiac conditions, so prescribing chloroquine prophylactically may not be prudent.

Despite the current hype for chloroquine and hydroxychloroquine, there have been clinical trials before with these drugs for other viruses, including dengue and chikungunya, which ended up as unsuccessful. Researchers wrote that the dose needed to have a significant effect on a virus was "just too high."

And because of this hype, some medical facilities are hoarding the drug resulting in some patients who rely on chloroquine for other conditions – including lupus and rheumatoid arthritis – complaining that they cannot get the medication because it is out of stock.

Research continues

As the chloroquine trails continue, other medications are also being studied for the treatment of COVID-19. Remdesivir, an investigational antiviral medication given via intravenous (IV) infusion, is one of these. Doctors are trying this medication on critically ill patients in clinical trials across U.S. hospitals. It is also available through a compassionate use program for patients who do not qualify for the clinical trials. Unfortunately, access to remdesivir is temporarily paused due to the overwhelming demand.

Researchers are also frantically working on a vaccine for COVID-19, and they may be closer to developing one than many realize. Today, there are at least 35 companies and academic institutions working on this, with at least four already testing in animals and one, the Boston-based biotech firm Moderna, nearly ready to begin human trials.

How did researchers arrive at human trials so quickly? It appears there are two reasons for this, one from the very place that this virus arose from.

First, early Chinese efforts to sequence the genetic material of Sars-CoV-2, the virus that causes Covid-19, allowed research groups around the world to grow the live virus and study how it invades human cells and makes people sick.

Second, earlier coronaviruses have caused two other recent epidemics – severe acute respiratory syndrome (Sars) in China in 2002-04, and Middle East respiratory syndrome (Mers), which started in Saudi Arabia in 2012. In both cases, work began on vaccines that were later shelved when the outbreaks were contained. One company, Maryland-based Novavax, has now manipulated those vaccines for Sars-CoV-2 and says it has several candidates ready to enter human trials this spring. Moderna Labs mentioned earlier as being nearly ready to enter human trials, built on its earlier work on Mers.

But until we find a treatment that is successful or a vaccine that works, the best advice to date remains very basic - practice social distancing and wash your hands frequently. It's the best we have at this point.

The author, Don Drake, oversees Connelly Law's Community Education Programming. He is a retired licensed clinician in the Commonwealth of Massachusetts with over three decades of experience working with older adults diagnosed with HIV/AIDS, substance abuse disorders, chronic homeless and mental illness. Prior to his retirement, he was the director of a unique treatment program for older adults with histories of mental illness, cognitive disabilities, and addiction at Shattuck Hospital in Boston. He was also a director at Steppingstone, Inc. in Fall River, Massachusetts where he was the clinical trainer, program and curriculum developer for the agency and oversaw treatment programming for older adults. He has over 40 years of human service and law enforcement experience and has worked as an administrator at programs in Boston, Hartford, Providence, and Philadelphia, helping to structure, hire and train staff in providing behavioral and addictions treatments for adolescents and adult clients. Drake also worked as a trainer for the Massachusetts Department of Public Health presenting training on QPR, a suicide prevention curriculum for the general public, the Massachusetts Council for Problem Gambling and the Crisis Prevention Institute, an international training organization that specializes in the safe management of disruptive and assaultive behaviors. He is also a retired professional wrestler who is in the New England Professional Wrestling Hall of Fame. Drake can be reached at Connelly Law Offices, Ltd.

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