Early on in the COVID-19 pandemic, hydroxychloroquine, an inexpensive anti-malarial drug with over 60 years of therapeutic use, showed promise in lab studies in battling the novel coronavirus, SARS-CoV-2.
But on Monday, the Food & Drug Administration (FDA) announced in a letter that it was revoking the drug of its Emergency Use Authorization (EUA) status to treat COVID-19.
In revoking the EUA, which was ordered on March 28, hydroxychloroquine will no longer be distributed from the Strategic National Stockpile (SNS), which is the United States’ national repository of antibiotics, vaccines, chemical antidotes, and other critical medical supplies. The SNS provides state and local municipalities with these supplies during public health emergencies.
In practical terms, the revocation of the EUA means that the FDA is asking doctors to stop using hydroxychloroquine on patients diagnosed with COVID-19.
Why The FDA’s About Face?
According to the letter, written by Rear Admiral Denise Hinton, the FDA’s Chief Scientist, “Based on new information, including clinical trial data results … this drug may not be effective to treat COVID-19 … and that the drug’s potential benefits for such use do not outweigh its known and potential risks.”
As you’ll read further on, the data that the FDA examined is just one of the controversies surrounding hydroxychloroquine. The drug is mired in controversy for other reasons as well.
President Trump & Hydroxychloroquine
Perhaps the biggest reason for the controversy surrounding the drug is that President Donald Trump has repeatedly touted it (some 50 times), despite a lack of positive clinical trials on the remedy, specifically for COVID-19. The President claimed to have preemptively taken a two-week course of the drug in hopes of avoiding becoming contagious.
There’s another controversial issue surrounding the drug and the President. The Trump family’s trusts contain a mutual fund investment. In this particular mutual fund, the largest holding is the pharmaceutical manufacturer (Sanofi) of a brand-name version of hydroxychloroquine (Plaquenil). Critics of the President argue that touting a drug in which he has a financial interest is a conflict of interest.
There’s plenty more controversy surrounding hydroxychloroquine. But for a brief moment, let’s take a detour and take a look at why the drug was considered a promising treatment for COVID-19 in the first place.
How Does Hydroxychloroquine Work Against Coronavirus?
Hydroxychloroquine and its more toxic close chemical cousin, chloroquine, are traditionally used to treat malaria and autoimmune disorders such as lupus and rheumatoid arthritis.
Just a few years ago, hydroxychloroquine (henceforth “HCQ”) was shown in a lab study to fight another virus that generated widespread panic: Zika virus. The mosquito-borne disease causes encephalitis (swelling of the brain) in newborns. In 2016 the medical journal, Viruses, showed that chloroquine blocks the process by which Zika enters the cells and replicates itself.
In lab tests, HCQ has been shown to prevent the SARS-CoV-2 virus from replicating in a similar fashion.
Specifically, here’s how HCQ works…. (If you’re not interested, skip to the next section.)
First, it alters the pH level of cellular components called endosomes and lysosomes. (Lysosomes are like the digestive system of the cell. Endosomes mature into lysosomes.) HCQ shifts the pH level of these cellular components towards a more alkaline state. This causes these cellular components to become dysfunctional; the virus can’t enter the cell and do damage.
Second, a medical student in a video references a study that shows how chloroquine helps the mineral, zinc, penetrate into the cells. Zinc can then prevent an enzyme that gets hijacked into making viral RNA; the virus is stopped from replicating its genetic code.
A 2010 study shows that zinc in the cells, paired with certain drugs that transport zinc across the fatty membrane of cells (such as HCQ), inhibits coronavirus.
Stay tuned because zinc is a part of the HCQ controversy. But before exploring more about the HCQ debate, there’s one more way in which HCQ may help battle coronavirus…
The third way HCQ works against coronavirus is by binding to sialic acid. Sialic acid is essentially the endpiece of a chain of sugar molecules attached to the surfaces of cells. The SARS-CoV-2 virus binds to this sugar molecule. HCQ prevents the spike protein in the coronavirus from binding to the sugary acid and causing a cytokine storm, which is an overreaction of the immune system.
Although these studies on HCQ seem convincing, they were conducted in vitro. In vitro studies are performed in cell cultures in petri dishes, not on humans.
Doctors Report Success Using HCQ Against COVID-19
Nonetheless, there has been anecdotal evidence that HCQ works for hospitalized COVID-19 patients. Most anecdotal reports suggest the drug is more effective if the disease has not progressed to a severe or critical state. Also, HCQ may be more effective in battling coronaviruses if it’s combined with zinc or antiviral drugs.
One proponent of HCQ treatment for COVID-19 is Joseph Varon, Chief Medical Officer of United Memorial Medical Center in Houston. Dr. Varon was profiled by a Houston NBC news affiliate and says he “swears by it.”
In the segment, Dr. Varon claims to have treated 100 COVID-19 patients in the hospital with HCQ. The patients treated with HCQ, he says, experienced a survival rate of more than 99%. “Hydroxychloroquine works,” he exclaims, adding that the drug usually takes 3-4 days of usage before patient outcomes are improved. Varon says that HCQ will help people recover as long as the drug is given early to patients, and if patients are monitored by a health professional. Varon plans on continuing to use the drug at least until a more effective remedy is made available.
Most doctors who support the use of HCQ do not recommend it in the way President Trump did, prophylactically. Rather, HCQ advocates advise taking it only for hospitalized patients and for use in clinical trials. (However, some governments such as India backs Trump’s use of the drug for virus prevention.)
A Dallas physician, Ivette Lozano, claims she successfully treated COVID-19 patients who were turned away from hospitals without receiving any treatment. In a speech, Lozano says she learned about treatment using HCQ through a press briefing by President Trump, who in turn, she says, learned about HCQ through its use in France.
Per an NPR report, France’s enthusiasm for HCQ was led by prominent researcher Didier Raoult. Raoult claimed to have had successfully treated COVID-19 patients using the drug in combination with azithromycin.
Why Did The FDA Pull The Plug on HCQ For COVID-19?
On May 22, an analysis of HCQ and chloroquine was published in The Lancet, one of the most influential peer-reviewed medical journals. The data analyzed was from 96,000 patients spread among 671 hospitals in six continents, and included patients hospitalized between Dec 20, 2019, and April 14, 2020. All patients tested positive for SARS-CoV-2.
The co-authors of the study wrote the following in their interpretation of the data:
“We were unable to confirm a benefit of hydroxychloroquine or chloroquine … for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias [abnormal heartbeat] when used for treatment of COVID-19.”
Shortly after the study was published, Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), and a key medical adviser on the White House coronavirus task force, said the following about HCQ in an interview aired on CNN:
“The scientific data is really quite evident now about the lack of efficacy.”
Three days after the Lancet study was published, the World Health Organization (WHO) halted hydroxychloroquine from being used in a smaller study on COVID-19 treatments.
A barrage of news reports on the seeming failure of HCQ to treat the disease and concern over its side effects ensued.
France’s health ministry subsequently barred the use of HCQ for treating COVID-19, asserting that recent studies show the treatment can produce “cardiac toxicity, particularly in combination with azithromycin.”
And in the United Kingdom, researchers abruptly stopped clinical trials on the efficacy of the malaria drug for the novel coronavirus.
End of story?
Hardly. The controversy continues….
Lancet Study Retracted For Data Integrity
On June 4, editors of The Lancet retracted the May 22 study that influenced the decision of the WHO and governments around the world to halt HCQ-COVID-19 clinical trials.
The reason for the retraction?
Three of the four co-authors seemed to be influenced by this open letter, signed by more than 200 scientists.
In the letter, the scientists called into question the veracity of the data. Their concerns were: 1) Patients were prescribed doses of hydroxychloroquine far higher than the FDA-recommended doses; 2) The hospitals that contributed patient data were not identified; 3) Inconsistencies between the number of patients in the study and data from government databases; 4) An unlikely amount of patients in Australia prescribed chloroquine as the drug is not available without special government authorization; 5) Data surrounding the deaths reported in Australia and Africa seem unlikely.
But perhaps the most egregious problem with the study is this….
The fourth co-author of the study, Sapan Desai, M.D., heads a small medical data analytics company called Surgisphere. Surgishpere, based in Chicago, was the company that collected the data on the 96,000 COVID-19 patients.
An investigation by the British media outlet, The Guardian revealed several troubling facts about Surgisphere, including:
- The three employees with the company have little or no data or scientific background, including one who is an “adult model.”
- The company has virtually no online or social media presence.
- Until earlier this month, the company’s “get in touch” link redirected to a WordPress template for a cryptocurrency website. The Guardian suggests this raises questions about how hospitals could easily contact the company to join its database.
- Desai, Surgisphere CEO, has been named in three medical malpractice suits, and his personal Wikipedia page has been deleted.
The three co-authors of The Lancet study asked for Surgishpere to have its data audited by a third party. Surgishpere refused. As a result, the three co-authors (minus Desai) of the Lancet study recommended to the editor to have these papers retracted.
(Another point of contention with the study is that zinc is not mentioned at all in the treatment protocol. As mentioned above, HCQ assists zinc in penetrating the cells, preventing the virus from replicating itself.)
New England Journal of Medicine Study Also Used Surgisphere Data
On the same day The Lancet retracted its study, the New England Journal of Medicine (NEJM), another influential peer-reviewed medical journal, retracted a study on COVID-19 therapies and heart disease that also used data by Surgisphere. Desai also co-authored the NEJM study.
The retraction says:
“Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.” We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”
What Is The Result of the Retraction?
The WHO has resumed allowing HCQ into its own COVID-19 therapy study (dubbed “Solidarity”).
But at present, HCQ’s reputation seems to have been permanently damaged.
Physicians who want to prescribe the drug for patients are having trouble getting prescriptions filled by pharmacists in several states, including New York, which based on an executive order by Governor Andrew Cuomo, has banned its use for COVID-19—unless the patient is part of a state-approved clinical trial.
Philippe Douste-Blazy, MD, is a cardiologist and a former French Health Minister who served as Under-Secretary General of the United Nations. A candidate in 2017 for Director of the World Health Organization, Blazy is featured in an interview on a French news station that aired on May 24. Blazy claims that in a closed door meeting with top medical experts, the editors of both The Lancet and the NEJM expressed their exasperation citing the pressures put on them by pharmaceutical companies. “Criminal” is the word they described for “the erosion of science.”
Blazy advocates the use of HCQ with azithromycin for Covid-19. This is the same combination that was recommended by the aforementioned French researcher, Didier Raoult. In April
Per AHRP.org, Dr. Douste-Blazy started a petition that has been signed by almost 500,000 French doctors and citizens urging French government officials to permit physicians to prescribe HCQ to treat coronavirus patients early, before they require intensive care.
What About The Risk of Side Effects From Hydroxychloroquine?
In a Fox Business segment, chairman of the Mayo Clinic’s COVID-19 Research Task Force, and infectious disease physician, Dr. Andrew Badley, first says that HCQ appears to have no effect in controlled clinical trials. “On the basis of those studies, it’s appropriate to stop studying the drug.”
As for the side effects of the drug, Badley goes on to say that “If you’ve already taken it and stopped it’s unlikely you’ll have them.” He adds that the side effects you can get from it can be serious or life threatening, such as heart arrhythmia, but those side effects will likely appear early on.
Professor Harvey Risch, M.D., Ph.D., is a researcher at the Yale School of Public Health with a specialty in cancer. Risch told the Yale Institute For Global Health that the combination of hydroxychloroquine and azithromycin has been used for decades in hundreds of thousands of people with rheumatoid arthritis. Although these two drugs when used in combination may cause a change in heart rhythm, these arrhythmias are still very rare in people using these medications.
“People who already have heart arrhythmias or are predisposed to them or have family histories of them should discuss this with their health care providers and see if using hydroxychloroquine plus doxycycline or some other medications would be a better choice,” Risch tells the Institute.
Risch adds that HCQ alone is not the whole story. “It needs to be combined with azithromycin or doxycycline and probably with zinc to make it most effective. The game changer is to aggressively treat people as soon as possible, before they are hospitalized, to keep them from becoming hospitalized in the first place.”
Why Is Hydroxychloroquine So Controversial: Conclusion
Perhaps this study published May 22 in The International Journal of Microbial Agents says it best, “Given that there is no cure for COVID-19, the clinical testing of HCQ is urgently needed to ascertain its potency against the virus as this is the current available treatment option.”