Hydroxychloroquine (HCQ) has become a highly-politicized, controversial drug, at least in the treatment of the novel coronavirus. Prior to the  pandemic, HCQ was a non-contentious medication, used mostly to prevent malaria, and as a therapeutic drug for the autoimmune disorders, lupus and rheumatoid arthritis. 

With several high-profile news stories in recent days involving HCQ, a sequel to the article “What is Hydroxychloroquine and Why is it so Controversial?” is warranted. 

Here are some of the key points from the first article:

• Since the early days of the pandemic, President Donald Trump touted the use of HCQ several times, and claims to have taken it to prevent contracting SARS-CoV-2, the disease caused by the novel coronavirus (Covid-19). 
• Several research studies show in cell cultures that HCQ, when used in combination with the mineral, zinc, and/or azithromycin and doxycycline, can prevent coronaviruses from multiplying. 
• Some independent doctors and researchers have claimed success in treating Covid patients with HCQ, 
• On May 22, The Lancet medical journal published a study which reviewed data of 96,000 Covid patients treated with HCQ. The study concluded: “We were unable to confirm a benefit of hydroxychloroquine or chloroquine … [HCQ] was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.” 
• After the Lancet study was published, 220 independent scientists published an open letter, questioning the veracity of the study, and the failure of the data to be verified by an independent, third-party.
• As a result of this letter, three of the four co-authors of the Lancet paper retracted their findings; The Lancet retracted the study two weeks after the initial publication. 
• The fourth author of the Lancet study is the CEO of the medical data company, Surgisphere, which compiled the data on the 96,000 patients. Both the Guardian and The New York Times ran investigations on Surgisphere that uncovered troubling findings about the company, including its small, medically-untrained workforce of three employees.
• Despite the retraction, the FDA announced it was revoking the drug from the national emergency stockpile, for use as a Covid-19 remedy. 
• Despite the retraction, Dr. Anthony Faucci, head of the National Institute of Allergies and Infectious Diseases said of HCQ in a CNN interview: “The scientific data is really quite evident now about the lack of efficacy.”

Hydroxychloroquine: Back In The Media Spotlight Thanks To “America’s Frontline Doctors”

In recent days, HCQ has re-emerged as a polemic issue, mostly for two reasons, the first being a video that President Trump tweeted of a small group of independent physicians, all wearing white lab coats emblazoned with the logo, “America’s Frontline Doctors.” The Doctors held a press conference in front of the Supreme Court building in Washington, D.C. The press conference was organized and sponsored by the Tea Party Patriots, a conservative-leaning activist organization. 

In the press conference, which was sparsely attended by the media, the doctors lambasted the fact that HCQ was being limited to clinical trials, and to hospitalized patients. The doctors argued that HCQ should instead be administered to Covid outpatients who demonstrate early onset symptoms; this is when HCQ has been deemed the most effective in observational studies. 

The Frontline Doctors claimed that the American public is being subjected to a misinformation and propaganda campaign, perpetrated by the corporate media and the largest technology companies. 

Shortly after another right-leaning organization, Breitbart.com, shared the video of the press conference on its Facebook page, Facebook removed the video. According to Breitbart’s website, the video was Facebook’s top-performing post on July 27th, having been viewed over 17 million times before being pulled. YouTube and Twitter also removed the post. 

Moreover, the website of America’s Frontline Doctors has gone dark. In response to the group’s website having been taken down without warning, board-certified physician and attorney, Dr. Simone Gold, founder of America’s Frontline Doctors (henceforth: AFD), tweeted:

“Our website host … has just completely and arbitrarily shut down our website, claiming a violation of their terms of service. We are a group of physicians advocating for a better understanding of COVID-19 and its available treatment options. This is outrageous.”

Why Do America’s Frontline Doctors Support Hydroxychloroquine For Coronavirus?

The doctors believe that “nobody needs to die” because of the novel coronavirus, pointing to their own experience successfully treating COVID patients with effective cures such as HCQ, “that are being censored for political reasons.”

In addition to the press conference, the doctors conducted a “White Coat Summit,” in which, among other issues, the doctors discussed research studies that show the merits of using HCQ both prophylactically, and as an early onset intervention in treating coronaviruses, as well as the case for reopening schools. 

One of the doctors who spoke at the press conference was Houston-based, Dr. Stella Immanuel. Immanuel claims to have treated over 350 COVID patients with HCQ, and none of them have died. Dr. Immanuel added that her success rate is 100% in treating Covid patients with HCQ, including patients with comorbidities such as diabetes, high blood pressure, and asthma. Immanuel’s oldest patient, she says, in the press conference, is 92. Her remedy for treating Covid patients is HCQ, zinc and Zithromax, “and they are all well,” Immanuel claims in the video.

“And, on top of that, I’ve put myself, my staff, and many doctors that I know, on Hydroxychloroquine, for prevention, none of us have gotten sick,” Immanuel claimed, adding, “[This is why] I came here to Washington D.C. to tell America, nobody needs to die! I’m upset! Why am I upset? Because I see people who cannot breathe. I see parents walk in, I see diabetics sitting in my office, knowing (thinking) that this is a death sentence! And they can’t breathe! And I help them, and I tell them it’s going to be OK. You’re going to live. And we treat them, and they live. None have died!”

It was perhaps Immanuel’s statements that have led to HCQ reemerging as a medical and political controversy. The video of her statement during the press conference was shared by President Trump and his son, Donald, Jr., before Twitter and Facebook took it down for violating their misinformation policy. 

Dr. Immanuel was the subject of an interview with a local Houston NBC affiliate. The interviewer asks Immanuel about her religious beliefs, which includes a belief in demon spirits that seek to have sex with unwitting victims while they sleep at night. Immanuel has been widely ridiculed by several media outlets.  

Yale Professor Backs Hydroxychloroquine For Covid-19 Treatment

The second event that catapulted HCQ back in the spotlight was an opinion article published in Newsweek, titled, “The Key to Defeating COVID-19 Already Exists. We Need to Start Using It,” written by a Yale University professor of epidemiology, Dr. Harvey Risch, M.D., Ph.D.

In his article, Risch describes HCQ as an inexpensive oral medication, which when given very early in the course of illness, before the virus has had time to multiply beyond control, has shown to be highly effective, especially when given in combination with the antibiotics azithromycin or doxycycline and the nutritional supplement zinc.”

Risch references an article he wrote published May 27 in the American Journal of Epidemiology (AJE) entitled, “Early Outpatient Treatment of Symptomatic, High-Risk COVID-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis.” The research in the peer-reviewed publication reviewed five studies, “demonstrating clear-cut and significant benefits to treated patients, plus other very large studies that showed [HCQ’s] safety.”

Hirsch writes in the Newsweek opinion: “Physicians who have been using these medications in the face of widespread skepticism have been truly heroic. They have done what the science shows is best for their patients, often at great personal risk.”

Dr. Hirsch continues, “I myself know of two doctors who have saved the lives of hundreds of patients with these medications, but are now fighting state medical boards to save their licenses and reputations. The cases against them are completely without scientific merit.”

Since the publication of Hirsch’s article, seven more studies on HCQ have shown similar benefits. Hirsch highlights the successes of some of these studies in the Newsweek article, including 400 high-risk patients, none of whom died. 

Hirsch also references the drug’s success in reducing Covid death rates in the Brazilain state of Pará, as well as in Switzerland, where, on the same day Hirsch’s AJE article was published (May 27), that country’s government banned the outpatient use of HCQ for COVID-19. Within a couple weeks of the ban, Hirsch claims the death rate in Switzerland increased four-fold. Consequently, the Swiss government revoked the ban, and by June 23, Hirsch says the death rate reverted to what it had been beforehand. 

Why Has Hydroxychloroquine Been Disregarded?

This is a question Hirsch raises in his Newsweek opinion piece. His answer is partly obvious: “The medication has become highly politicized. For many, it is viewed as a marker of political identity, on both sides of the political spectrum.” The results of this polarization, Hirsch suggests, is tragic.

“Nobody needs me to remind them that this is not how medicine should proceed. We must judge this medication strictly on the science. When doctors graduate from medical school, they formally promise to make the health and life of the patient their first consideration, without biases of race, religion, nationality, social standing—or political affiliation. Lives must come first.”

Hirsch brings to the fore another reason for the dismissal of HCQ by health authorities, one that is not well-reported by the media. To quote Hirsch, “The drug has not been used properly in many studies.”

Hirsch is likely referring to two prominent research trials:

• Recovery: A large clinical trial being conducted in the UK, currently involving four remedies (previously six). HCQ was discontinued as a remedy because it was deemed ineffective for hospitalized patients. The study is being conducted at Oxford University, and is sponsored by Mastercard, the Wellcome Trust (which was acquired by GlaxoSmithKline) and the Bill and Melinda Gates Foundation and the UK government. Recovery is one of the first investments to come from the COVID-19 Therapeutics Accelerator, a large-scale initiative launched by the Bill & Melinda Gates Foundation.
  
• Solidarity: Over 100 countries are participating in this phase 3-4 clinical trial, organized by the World Health Organization (WHO). The study participants, all of whom have severe Covid-19 symptoms, are currently administered one of four treatments. HCQ was withdrawn twice as a treatment, most recently in early July, because, like Recovery, it was not shown to be effective for hospitalized patients.
  

Despite the findings of the Recovery and Solidarity trials, Hirsch defends HCQ, arguing, “Hydroxychloroquine has shown major success when used early in high-risk people but, as one would expect for an antiviral, much less success when used late in the disease course.”

But even for hospitalized patients, Hirsch suggests that there is evidence to back HCQ as a Covid-19 intervention. “It has demonstrated significant benefit in large hospital studies in Michigan and New York City when started within the first 24 to 48 hours after admission.”

The proper way to administer HCQ, says Hirsch, is to give the medication in high-risk patients “immediately upon clinical suspicion of COVID-19 disease, without waiting for results of testing. Delays in waiting before starting the medications can reduce their efficacy.”

This calls into question why none of the world’s largest health organizations such as WHO have conducted a clinical trial on the use of HCQ as an early intervention….

What About Heart Problems And Hydroxychloroquine?

Hirsch addressed the issue of HCQ and cardiac arrhythmia in part 1 of this article, arguing that the combination of hydroxychloroquine and azithromycin rarely causes arrhythmias. In the Newsweek article Hirsch suggests that the claim by leading health organizations such as WHO and FDA, that HCQ causes cardiac distress, is unfounded. Hirsch points to the FDA’s Adverse Event Reporting System that lists roughly 1000 cases of arrhythmias attributed to HCQ use. 

While Hirsch acknowledges that the number of arrhythmias is likely much higher, he says that what the FDA did not announce is that these adverse events were generated from tens of millions of patient uses of HCQ for long periods of time, often for the chronic treatment of lupus or rheumatoid arthritis. 

“Even if the true rates of arrhythmia are ten-fold higher than those reported, the harms would be minuscule compared to the mortality occurring right now in inadequately treated high-risk COVID-19 patients,” Hirsch writes. 

Hirsch did not cite in his article a study published in Circulation, a peer-reviewed journal of the American Heart Association, titled “The Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection.” 

The QT interval is a measurement made on an electrocardiogram, which records electrical impulses of the heart. Abnormally long or short QT intervals are associated with an increased risk of developing abnormal heart rhythms and sudden cardiac death. The findings from the Circulation study, which at the time of its publication in April was the largest reported observational study of Covid-19 patients treated with HCQ, found no instances of rapid or irregular heart beat. “Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy,” the study concluded. 

Were Solidarity and Recovery Patients Given Toxic Doses of HCQ?

Hirsch alleges in the Newsweek article that HCQ “has not been used properly in many studies.”

Some critics of the Recovery and Solidarity studies, such as the Alliance for Human Research Protection claim that hospitalized patients with severe Covid-19 symptoms were administered toxic doses of HCQ. 

In one such study, the so-called REMAP-CAP trial, some patients administered HCQ were already on a ventilator at the time the controversial drug was administered. 

Meryl Nass, M.D., a member of the board for The Alliance for Human Research Protection, and a physician in Maine, argues that “Such patients are hardly capable of giving consent. Rather than attempting to save their lives, they are being given multiple high doses of hydroxychloroquine and other drugs whose combination is contraindicated.”

The Politicized Hydroxychloroquine Debate Is Worldwide

While President Trump has been a key figure of the HCQ controversy, another world leader that has touted its benefits has made recent headlines. Brazilian President Jair Bolsonaro claimed HCQ saved his life after testing positive for Covid-19 and developing symptoms. 

“I’m healed from Covid. I have antibodies, no problems. In my particular case, I first thank God, and secondly, the medication prescribed by the presidential doctor: hydroxychloroquine,” Bolsonaro said in an address. 

Despite Bolsonaro’s claim and the studies Hirsch alludes to in the Newsweek article, CNN’s article about the Brazilian leader says, “Numerous studies have shown that the drug — also touted by US President Donald Trump — is ineffective against Covid-19, and may even be harmful.”

CNN’s reporting fails to mention that the influential Lancet study was retracted. 

And because of the lag time of the publication and retraction (two weeks), and because of the dearth of reporting on the retraction, some states followed the FDA’s recommendation to discontinue HCQ as a Covid-19 intervention. 

In Ohio, that state’s Board of Pharmacy issued a rule that prohibited the use of hydroxychloroquine and chloroquine (a more toxic version of HCQ) to treat Covid-19. However, on July 31, as a result of the feedback received by the medical and patient community and at the request of the state’s Republican Governor, Mike DeWine , the Board backed off its ban of HCQ, Cleveland.com reports. 

Likewise, the state of Texas’ Pharmacy Board loosened restrictions on dispensing HCQ prescriptions. 

Conclusion: Why is Hydroxychloroquine So Controversial? 

Revisiting Hirsch’s Newsweek article, the Yale professor writes he hopes that in the future, that “This misbegotten episode regarding hydroxychloroquine will be studied by sociologists of medicine as a classic example of how extra-scientific factors overrode clear-cut medical evidence.”

Hirsch continues, “But for now, reality demands a clear, scientific eye on the evidence and where it points. For the sake of high-risk patients, for the sake of our parents and grandparents, for the sake of the unemployed, for our economy and for our polity, especially those disproportionally [sic] affected, we must start treating immediately.”

Hirsch also could have added to this list the thousands of front line medical workers, such as Dr. Joseph Costa, Chief of Critical Care at Baltimore’s Mercy Medical Center, who died July 27 from Covid-19 complications. 

The HCQ controversy is unlikely to fade anytime soon. (Perhaps a part 3 will be published in the near future, and will include information on the expensive antiviral drug, Remdesivir, which just completed a phase 3 trial for patients with moderate Covid-19 symptoms. Remdesivir costs over $3,000 for one treatment course. The cost of HCQ for 100 tablets: less than $50.