• Alison Kartevold

The Chloroquine Controversy

Trump likes its chances, the media and his opponents laud the risks, and doctors want more data. The controversy concerning whether or not a hydroxychloroquine regiment can decrease COVID-19 deaths is raging. Gist Say'n explains why.

The pandemic has spread to at least 184 countries around the world, and we are about a month in on the nation's attempt to slow the spread of COVID-19 by shutting down and staying home. As of April 10th, the United States has more than 460-thousand confirmed cases and over 16-thousand deaths.

A number you don't hear nearly as often is that so far, more than 26-thousand people with confirmed cases have recovered from the disease in the United States. Also, the curve of cases in New York might be plateauing, with the death rate coming in well below worst-case scenario model predictions.

During the April 7th COVID Task Force briefing at the White House, Dr. Anthony Fauci said people across the entire country should be proud of what they've accomplished through social distancing so far because we have gotten to this point due to mitigation. While that is excellent news, the country can not afford to stay locked down forever. So as the United States begins to flatten the coronavirus curve, talks turn to how to go about reopening the country as quickly as possible without causing a relapse.

Developing a new vaccine and deploying it to the masses is months if not a year or more away. The next great hope is to find an already existing drug or set of drugs that can at least slow the spread of COVID-19 while people return to work and begin to try and salvage their lives and the economy.

The Gist of It

Studies out of China and France, along with a growing number of anecdotal accounts from doctors treating patients indicate that a mix of drugs that include hydroxychloroquine might help in the war against COVID-19. With these reports also come concerns.

Topping the list of medical concerns is that despite the anecdotal evidence, the drug may not work, or even worse, it could cause harm. Scientists are generally conservative by nature and worry that false hope leads to a loss of credibility. They never want to be "the boy that cries wolf."

Doctors already prescribing hydroxychloroquine for other aliments fear the impact a run on the drug can cause their patients. The United States does not have a stockpile large enough to treat everyone, and companies are not yet making the drug in our own country. Mylan pharmaceutical is, however, bringing a plant in West Virginia online to produce it.

So currently we are heavily reliant on other countries, like China and India, to provide it, which brings us to the political side of the concerns.

You might have noticed that about the time hydroxychloroquine came into the limelight was also when President Trump stopped calling COVID-19 the "China Virus." Whether or not we end up needing more hydroxychloroquine or something else, we are currently at China's mercy when it comes to medications.

In 2019, a U.S. Department of Commerce study reported that 97 percent of all antibiotics in the United States come from China. Rosemary Gibson, the author of China Rx, says that the United States has virtually no capacity to make most generic antibiotics. She says China controls 80 percent of the ingredients used to make to all of the world's medicines.

Other political concerns arise due to money and Donald Trump. This drug is cheap. It has been around so long that patents have run out, meaning any drug company that chooses can make it in a generic form. If it works, no one company is going to corner the market and strike it rich by developing a new cure.

If it works, it would also mean that President Trump was right to have the federal government buy and distribute the medication in mass, as he is trying to do right now. The countless lives saved and the ability to quickly reopen the country would make him a heroic figure. Heroes always do better come reelection time.

Attorney General William Barr says, "The media has been on a jihad to discredit the drug." Indeed, many media outlets and pundits have proclaimed the drug as dangerous and promotion of its use as irresponsible. Yet, as Peter Navarro, assistant to the President told CNN's, John Berman, healthcare professionals on the front line are now both prescribing the medication to COVID-19 positive patients and taking it themselves as a prophylactic.

If in the coming weeks, the majority of our healthcare workers remain uninfected, that could become another compelling anecdotal case in favor of the drug's use.

How We Got Here

During a pandemic, there is always a race to come up with ways to prevent, weaken, or cure the disease responsible for disrupting the entire world. People voluntarily give up civil liberties, governments cut regulatory red tape, and money is no object until a solution is found.

Ideally, politics would not play a role, but in the real world, they do. These include not just government politics, but medical politics. All of which brings us to the now politicized debate over hydroxychloroquine because thus far, it is the most talked-about drug prospect for possible relief for this pandemic.

For decades hydroxychloroquine, and its predecessor chloroquine, have been used around the world to treat malaria. It is also routinely used to treat lupus and rheumatoid arthritis.

It showed some promise during the last fight against SARS, so it was one of the first drugs doctors on the front line in China turned to when desperate for something, anything, that would slow down the COVID-19 virus. Chinese physicians were the first to offer evidence that the drug was helpful.

On March 20th, French doctors published results from a study indicating that when a combination of hydroxychloroquine and azithromycin, an antibiotic, was given to patients with COVID-19, they saw positive results.

This same team in Marseille released another report that caused controversy on March 27th, which involved 80 patients. In it, they reported a "clinical improvement compared to the natural progression." They reported seeing a significant reduction in the viral load in 83 percent of their patients on day seven of treatment and said that 93 percent of those patients had negative results on day eight. The investigators said, "we noted a clinical improvement in all but one 86-year-old patient who died, and one 74-year-old patient still in the intensive care unit."

"This allowed patients to rapidly be discharged from highly contagious wards with a mean length of stay of five days," investigators wrote. "We believe other teams should urgently evaluate this cost-effective therapeutic strategy, to both avoid the spread of the disease and treat patients as soon as possible before severe respiratory irreversible complications take hold."

Given the circumstances under which they did the study, the doctors involved said they were not willing to give a placebo treatment to any of their patients. So while the data might seem encouraging, the lack of a control arm in the study has left medical researchers skeptical.

This study and other anecdotal evidence from individual doctors who began prescribing their own off label cocktails to patients very early on caused President Trump to take notice, and he pushed for the FDA to approve the compassionate use of the drug.

On March 28th, the Chief Scientist of the FDA issued an Emergency Use Authorization for healthcare providers to prescribe hydroxychloroquine distributed from the Strategic National Stockpile. It stated that the drug could be given to patients hospitalized with COVID-19 for whom a clinical trial is not available, or participation is not feasible.

Dr. Andre Kalil, a professor at the University of Nebraska Medical Center in Omaha, is among those scientists emphasizing the need for randomized controlled trials. In an article for the Journal of the American Medical Association, Dr. Kalil said the problem with off-label use and compassionate use of drugs is the interpretation of the results. If the patient dies, the assumption is that he or she died of the disease, but if the patient survives, the assumption is he or she survived because of the given drug, but "this is not true," he said. "Without a control group, we can never, ever safely find new medications for any disease."

Dr. Kalil, who is leading a COVID-19 clinical trial, says there is no way to know whether patients benefit from a drug or are harmed by it without a randomized clinical trial. He and other leading researchers agree that the well-established principle of evidence-based medicine should not be forgotten during a crisis.

Multiple clinical trials are underway and have begun in record time. They aim to determine whether

hydroxychloroquine and chloroquine can help as either a prophylactic or treatment of patients with mild, moderate, and severe COVID-19.

The challenge is none of these studies will likely yield definitive results fast enough to make a difference during the peak of this pandemic, which is why President Trump says he wants doctors to consider using it off label while the clinical trials proceed. His approach is beyond the comprehension of his detractors and is resulting in contentious accusations. In one such exchange with CNN's Jay Diamond, Trump said, "I don't want it to be a lab for the next year and a half as people are dying all over the place."

As cases of hospitalization, intubation and death begin to plateau in New York, members of the President's COVID-19 task force want to keep the focus on social distancing.

"We got there through mitigation," Dr. Fauci started saying at the April 6th press briefing before adding that currently, this is our best and most effective health tool.

Dr. Vladimir Zelenko, who treats the Hasidic Jewish community of Kiryas Joel in New York, said he understands the need for clinical trials but added that ignoring a hopeful treatment is also risky.

"I'm a strong supporter of clinical trials," he said. "But they take time, and that's one thing we don't have. The virus is here, it's World War III, and not everyone has fully comprehended that yet."

So about three weeks ago, the self-described country doctor took to YouTube to share his views. Dr. Zelenko wants to see a combination of drugs he has prescribed used in more outpatient care. He says he has treated hundreds of patients in his community for the novel coronavirus. For those at the most significant risk, he has prescribed a cocktail of hydroxychloroquine, azithromycin, and zinc. The doctor believes his treatment has kept the disease from progressing, limiting the need for hospitalization and saving the lives of 383 of his patients.

His regimen is based on a hybrid of research from South Korea and the studies conducted in France.

Though not clinically proven, Dr. Zelenko is so confident of its potential impact he posted a google docs letter to President Trump, calling on him to have an emphasis placed on "preemptive treatment for high-risk patients in the outpatient setting - primary care and urgent care settings."

For his effort, he faces vilification in the media and by some in his own profession. One account described him as a "conspiracy-peddling doctor."

Undaunted, Zelenko also sent a letter to Isreal's Health Ministry director-general urging that his protocol be adopted there as well.

“In summary, it is imperative to initiate aggressive and early treatment of COVID-19 in the primary care setting, before the patient develops pulmonary complications,” the doctor wrote in his letter. "According to my data, prompt treatment will reduce hospitalizations, intubation and death. I humbly and respectfully request that you consider this outpatient treatment against COVID-19.”

The White House and countless doctors around the world are willing to try a similar approach.

Sermo, a secure digital (online) platform designed for physician networking and anonymous survey research, surveyed 6,227 physicians across all specialties in 30 countries. Between March 25th through the 27th, these physicians chose hydroxychloroquine as the most effective therapy from a list of 15 options (37% of COVID-19 treaters).

There is still an emphasis on caution, though. This treatment is experimental and may not work. It can cause side effects and needs to be administered under a doctor's direction and supervision.

April 10th the CDC's website still said:

"There are no drugs or other therapeutics approved by the U.S. Food and Drug Administration to prevent or treat COVID-19. Current clinical management includes infection prevention and control measures and supportive care, including supplemental oxygen and mechanical ventilatory support when indicated. Interim guidelines for the medical management of COVID-19 will be provided soon by the Department of Health and Human Services COVID-19 Treatment Guidelines Panel."

Until then, however, it appears that hydroxychloroquine is the best long shot doctors have at their disposal, and a majority of those surveyed by Sermo believe the country is striking the correct balance between public health and economic politics. According to its findings, an overwhelming majority, 72 percent believe the United States is weighting public health concerns and economic concerns appropriately.

You can agree or disagree, it's okay, cause I'm gist say'n.