How effective is Hydroxychloroquine for treating the novel coronavirus COVID-19?
In March 2020, U.S. President Donald Trump touted hydroxychloroquine as an effective treatment for coronavirus disease 2019 (COVID-19). Mr. Trump highlighted the drug cocktail of hydroxychloroquine and azithromycin as “one of the biggest game changers in the history of medicine.”1 But how effective is hydroxychloroquine in combating COVID-19 in actuality?
What is Hydroxychloroquine?
First, we must understand what hydroxychloroquine is: an anti-malarial drug, used to treat malaria, lupus erythematosus, rheumatoid arthritis, and porphyria.2 The drug was first synthesized in the 1940s, and along with a similar variant minus the hydroxyl group – chloroquine, of greater toxicity than hydroxychloroquine – has been designated by the World Health Organization as an essential medicine for its clinical efficacy and cost-effectiveness.3 4
Hydroxychloroquine is an anti-malarial drug created in the 1940s
In the midst of the 2019-20 coronavirus pandemic, hydroxychloroquine was repositioned to determine its efficacy against COVID-19. One of the earliest clinical trials took place from February 4 to February 28, 2020 with sixty-two patients at Wuhan University’s Renmin Hospital in Hubei Province, China, where the index case was identified.5
Clinical Results on Hydroxychloroquine Treatment for COVID-19
The study found that when compared with the control group, 80.6% of patients receiving hydroxychloroquine saw improvement to their pneumonia condition when compared with only 54.8% of those in the control group not receiving hydroxychloroquine.5 Furthermore, although two patients reacted adversely to hydroxychloroquine treatment, “the body temperature recovery time and the cough remission time were significantly shortened” for those taking the drug.5
A similar Chinese study in March investigated the means by which hydroxychloroquine inhibits COVID-19 in vitro. According to the study, the drug’s efficacy is predicated on “the alkalinization of the intracellular phagolysosome, which prevents virion fusion and uncoating and, therefore, viral spread.” 6 7 A study in France corroborated the Wuhan study and expounded upon it with the efficacy of drug cocktail of hydroxychloroquine and azithromycin.7 8
Insufficient Research Evidence on Efficacy of Hydroxychloroquine for COVID-19 Treatment
However, the medical community has deemed extant research insufficient to suggest a causal relationship between the administration of either hydroxychloroquine or the drug cocktail hydroxychloroquine and azithromycin and the potent inhibition of viral spread or mitigation of pneumonia and other COVID-19 symptoms. Rajesh Gandhi, a doctor at Massachusetts General Hospital and professor at Harvard Medical School, said that the Infection Diseases Society of America deemed “that the data so far for hydroxychloroquine and chloroquine is insufficient to be either for or against it. We don’t know that it doesn’t work or that it works.”9
“We don’t know that it doesn’t work or that it works.” ~ Dr. Rajesh Gandhi at Harvard Medical School
Concerns about Hydroxychloroquine Safety as COVID-10 Treatment
In fact, there exist concerns about the safety of hydroxychloroquine and chloroquine as treatment for COVID-19. Earlier findings of adverse responses to the former in Wuhan were corroborated by a Brazilian study where when patients were given a larger dosage of chloroquine, the lethality rate increased to 17%, a dramatic increase from the 13% baseline rate as found in studies not using chloroquine.10 The Brazilian study’s results appear to demonstrate that a high dosage of chloroquine, more toxic than hydroxychloroquine, can have adverse effects.
Side Effects of Hydroxychloroquine
One of the side effects of hydroxychloroquine has also emerged as a concern: ventricular arrhythmia. The American College of Cardiology (ACC) has stated that hydroxychloroquine has been found to lead to QT prolongation, by which the QT intervals recorded by an electrocardiogram are farther apart, indicating that the heart takes longer to recharge between beats.11 QT prolongation is associated with greater risk for sudden cardiac death (SCD) and torsades de pointes (TDP).11 The former involves impairment or termination of the heart’s function, leading to death; the latter is an abnormal heart rhythm that can lead to SCD.11 Although the ACC notes that instances of QT prolongation in patients taking hydroxychloroquine remains low, the inherent safety concerns lead them to regard the drug as high-risk, but that this can be reduced by close monitoring of patients.11
Hydroxychloroquine can cause heart arrhythmia in the ventricles.
Cardiotoxic Risks for Hydroxychloroquine Use
A 2018 study suggested that in response to a patient developing an arrhythmia, terminating hydroxychloroquine’s use by the patient may be conducive to mitigating any fatal effects.12 However, a 2013 study found that two months after a fifty-two-year-old woman’s arrhythmic heart condition was diagnosed and her intake of hydroxychloroquine was terminated, the result was still fatal.13 This led researchers to believe that the inherent cardiotoxicity risk that some patients experience from hydroxychloroquine may render the suspension of drug administration futile, particularly in instances in which the cardiotoxicity induces irreversible histopathological changes, or tissue alteration.13
Conclusion on Efficacy of Hydroxychloroquine
It is important to note that although QT prolongation may be exhibited less commonly by hydroxychloroquine users, the lack of understanding as to the risk factors for sudden cardiac death emanating from the drug’s usage render it high-risk. Irreversible tissue changes by hydroxychloroquine-induced cardiotoxicity can be irreversible in some patients. With regard to any amelioration of condition in patients with COVID-19, extant research is still insufficient to make any determinations as to the drug’s efficacy in combating the disease. Therefore, although in isolated instances the drug has been shown to lead to an amelioration in COVID-19 patients’ condition, a significant lack of research on the causal relationship between hydroxychloroquine and the inhibition of viral spread, as well as potentially fatal side effects with the more toxic agent chloroquine, have led the scientific community to neither affirm nor deny the drug’s efficacy. Its high-risk nature continues to be maintained by the ACC’s drug guidelines.
1. Trump, Donald J. “HYDROXYCHLOROQUINE & AZITHROMYCIN, Taken Together, Have a Real Chance to Be One of the Biggest Game Changers in the History of Medicine. The FDA Has Moved Mountains – Thank You! Hopefully They Will BOTH (H Works Better with A, International Journal of Antimicrobial Agents)…..” Twitter, Twitter, 21 Mar. 2020, twitter.com/realDonaldTrump/status/1241367239900778501.
2. “Hydroxychloroquine: MedlinePlus Drug Information.” MedlinePlus, U.S. National Library of Medicine, medlineplus.gov/druginfo/meds/a601240.html.
3. “Hydroxychloroquine: Benefits, Side Effects, and Dosing.” Lupus Foundation of America, http://www.lupus.org/resources/drug-spotlight-on-hydroxychloroquine.
4. “Essential Medicines.” World Health Organization, World Health Organization, 15 Feb. 2016, http://www.who.int/medicines/services/essmedicines_def/en/.
5. Chen, Zhaowei, et al. “Efficacy of Hydroxychloroquine in Patients with COVID-19: Results of a Randomized Clinical Trial.” MedRxiv, Cold Spring Harbor Laboratory Press, 1 Jan. 2020, http://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3.
6. Yao, Xueting, et al. “In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).” Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, Oxford University Press, 9 Mar. 2020, http://www.ncbi.nlm.nih.gov/pubmed/32150618.
7. Vincent, Jean-Louis, and Fabio S Taccone. “Understanding Pathways to Death in Patients with COVID-19.” The Lancet. Respiratory Medicine, Elsevier Ltd., 6 Apr. 2020, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159849/.
8. Gautret, Philippe, et al. “Clinical and Microbiological Effect of a Combination of Hydroxychloroquine and Azithromycin in 80 COVID-19 Patients with at Least a Six-Day Follow up: A Pilot Observational Study.” Travel Medicine and Infectious Disease, Published by Elsevier Ltd., 11 Apr. 2020, http://www.ncbi.nlm.nih.gov/pubmed/32289548.
9. Weise, Elizabeth. “Study of Trump-Touted Chloroquine for Coronavirus Stopped Due to Heart Problems, Deaths.” USA Today, Gannett Satellite Information Network, 15 Apr. 2020, http://www.usatoday.com/story/news/2020/04/15/coronavirus-chloroquine-test-halted-drug/2983129001/.
10. Barba, Mayla Gabriela Silva. “Chloroquine Diphosphate in Two Different Dosages as …” MedRxiv, Cold Spring Harbor Laboratory, 16 Apr. 2020, http://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1.
11. “Ventricular Arrhythmia Risk Due to Hydroxychloroquine-Azithromycin Treatment For COVID-19.” American College of Cardiology, 29 Mar. 2020, http://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/ventricular-arrhythmia-risk-due-to-hydroxychloroquine-azithromycin-treatment-for-covid-19.
12. Zhao, Hang, et al. “Hydroxychloroquine-Induced Cardiomyopathy and Heart Failure in Twins.” Journal of Thoracic Disease, AME Publishing Company, Jan. 2018, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863196/.
13. Joyce, Emer, et al. “Hydroxychloroquine Cardiotoxicity Presenting as a Rapidly Evolving Biventricular Cardiomyopathy: Key Diagnostic Features and Literature Review.” European Heart Journal. Acute Cardiovascular Care, SAGE Publications, Mar. 2013, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760572/.
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