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05/10/2020

We have all seen the drug Hydroxychloroquine/Chloroquine gaining too much fame among the public these days. As soon as it was discovered that it is effective against COVID, at least to some extent, governments around the world began to import it in large numbers. President of the United States, Donald J. Trump even regarded it as a game-changer in the history of medicine. 

An image depicting structural proteins of the SARS-CoV2.
Image by Lecturio.

Its demand rose as the COVID situation worsened in areas such as the United States and the United Kingdom. WHO has warned the world of its side-effects and has stated that further research is sought in the direction before it can be used as a treatment. Hydroxychloroquine is potentially dangerous to patients with chronic heart diseases.

 

As of April 25, according to the Centers for Disease Control and Prevention(CDC) website, there are no drugs or other therapeutics presently approved by the U.S. Food and Drug Administration (FDA) 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.

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A study on “Efficacy and Safety of Hydroxychloroquine for Treatment of COVID-19″ published by the Shanghai Public Health Clinical Center, China in the U.S. National Library of Medicine has concluded that:

The prognosis of common COVID-19 patients is good. Larger sample size studies are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments.

Viral load was also found to be decreased in the pharyngeal swabs of patients in the experimental group, the study has suggested.

According to a paper published by the WHO on cardiac toxicity of antimalarials in 2016,

Antimalarial medicines that can induce QT/QTc interval prolongation should be used with caution in individuals with known heart disease, a family history of sudden unexplained death consistent with cardiac arrhythmias, or who are already taking medicines that can prolong the QT/QTc interval.

Further studies are needed to identify genetic polymorphisms and other pre-existing conditions that may contribute to the risk of drug-induced cardiotoxicity.

 

How is chloroquine of use in dealing with COVID-19?

It is worth wondering though, how can CQ/HCQ( antimalarials ) help treat COVID( caused by the SARS-CoV2 virus). Malaria is caused by a protozoan, Plasmodium. How can they then be effective against a disease caused by a virus? The probable rationale behind this has been that CQ/HCQ increases surface pH and does not let the cell and virus interact.

Chloroquine increases endosomal pH and interferes with the glycosylation of cellular receptors of SARS-CoV and thereby it has the potential to block viral infection. In addition, chloroquine also inhibits the quinone reductase-2, which is involved in sialic acid biosynthesis (an acidic monosaccharides of cell transmembrane proteins required for ligand recognition) that makes this drug a broad antiviral agent.

The use of Chloroquine/Hydroxychloroquine has been approved for other diseases such as rheumatoid arthritis and lupus(SLE)

Both the drugs( Chloroquine Phosphate and Hydroxychloroquine Sulfate) have shown to inhibit SARS-CoV2 in-vitro but there is no scientific evidence to back it. Clinically, it still requires many human trials. Hitherto, no clinical trial has been published in any journal that can satisfactorily support the rationale.

Image by shutterstock.

On  March 28, the FDA had granted an emergency authorization for the use of Hydroxychloroquine for hospitalized patients. However, the FDA had clarified that these drugs can be used as a treatment for hospitalized COVID patients and its use outside the hospital-setting should be prohibited. It had stated that it should be administered only on the valid prescription of a registered medical practitioner. 

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The medicines being used under the hydroxychloroquine/chloroquine EUA(Emergency Use Authorization) are supplied from the Strategic National Stockpile, the national repository of critical medical supplies to be used during public health emergencies.

It has been hypothesized that the mechanism of entry of SARS-CoV2 is much similar to that of SARS-Cov1. Chloroquine and Hydroxychloroquine seem to block the entry of SARS-CoV1 into host cells by inhibiting glycosylation of host receptors(ACE Receptors), proteolytic processing, and endosomal acidification. This supports the rationale of CQ/HCQ use against SARS-CoV2.

Why does it cause QT prolongation?

An image depicting a prolonged QT interval.
Image by Mayo Clinic.

The QT interval on the surface EKG represents the summation of action potential (AP) of ventricular myocytes. The action potential reflects the flow of ion currents across a cell membrane through specialized channels made of protein complexes. Malfunction of these protein channels can lead to either increased inward current or reduced outward current. This subsequently increases the action potential duration and hence QT interval prolongation.

 

The risk of QT/QTc prolongation is increased in cases where it is administered along with a macrolide antibiotic(eg. Azithromycin). It then causes ventricular tachycardia and arrhythmias. Patients who also have other health issues such as heart and kidney disease are likely to be at increased risk of these heart problems when receiving these medicines. 

Should you self-medicate yourself with CQ/HCQ?

The answer is a strict NO. You shouldn’t take it unless specified by a registered medical practitioner. At no cost should you intake the drug or think of it as a prophylaxis against COVID. It is being highlighted here that the FDA has approved its use only for hospitalized COVID patients. There are still speculations leading us to believe that taking it could actually worsen your health. Following is a case that should serve as a deterrent against the use of CQ/HCQ by the common man.

An Arizona man died and his wife got hospitalized after they took a form of the same drug. CQ is commonly used in aquariums to clean them. The couple took it from the aquarium and suffered the effect within 30 minutes of ingestion. So you shouldn’t be taking it unless the FDA or any clinical trial has proved otherwise.

Common Side-effects of CQ/HCQ:

  • Upset stomach.
  • Headache
  • Diarrhea
  • Skin rash 
  • Itching 
  • Hair Loss
  • Heart problems

Other investigational, empiric therapies, and advancements:

  • Hyper-immune Plasma Therapy
  • Remdesivir
  • Lopinavir-Ritonavir
  • Tocilizumab
  • Camostat-Mesylate
  • mRNA-1273 vaccine

Abbreviations Used:

  • CQ-Chloroquine
  • HCQ-HydroxyChloroQuine
  • mRNA-messenger RNA
  • FDA-Food and Drug Administration
  • CDC-Centers for Disease Control and Prevention
  • ACE-Angiotensin Converting Enzyme
  • QTc-Corrected QT interval
  • EKG-Electrocardiogram
  • SLE-Systemic Lupus Erythematosus

References and Further reads:

  1. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?
  2. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.
  3. U.S. National Library of Medicine: Interventional Studies on COVID
  4. Coronaviruses: An Overview of Their Replication and Pathogenesis
  5. CDC: Healthcare Infection Prevention and Control FAQs for COVID-19

Authors:

Harsh Rai-NMCTH

Himanshu Jindal-GSVM Medical College

 

Special Thanks to Dr. Rajnish Raj Sir(State President IMA MSN UP) for his support and guidance.


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16 thoughts on “Hydroxychloroquine- All you need to know”

    1. Good initiative! And really inspiring to all the medical students to be updated about the current COVID-19 scenario,
      Beautifully written,
      Keep it up!!

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