Is Hydroxychloroquine effective for treatment of COVID-19?

With the President of the United States extolling the virtues of Hydroxychloroquine and world supply suddenly under strain, the question remains is it an effective treatment or miracle drug against the virus. Is there evidence behind the claims of an effective treatment for COVID-19?

The short answer is we don’t really know if Hydroxychloroquine has a meaningful effect on humans. Hydroxychloroquine is the second generation of the anti-malarial drug Chloroquine that saw widespread use as an anti-malarial in the 1950’s until malaria developed resistance to the drug. Hydroxychloroquine is a chloroquine derivative that is most commonly used at present for autoimmune diseases such as Lupus or Rheumatoid Arthritis in the West. Chloroquine and Hydroxychloroquine do have some anti-viral effects, both drugs can increase the pH in lysozymes on a cellular level which inhibits the release of the virus.¹ These drugs can also act as Zinc ionophores that transport Zinc into the cell which can inhibit viral replication.²

In a French study that has been cited quite often for the beneficial effects of Hydroxychloroquine for the treatment of COVID-19, the researchers found the reduction of viral load that was enhanced with the addition of Azithromycin.³ Why Azithromycin, an antibiotic that is commonly used for bacterial pneumonia, would have any effect against a COVID-19, viral pneumonia, is unclear.  The criticisms of the study center around the small sample size (28 patients), and the study was unblinded. Most importantly, the study did not establish if the regimen had any effect on the clinical outcome of the patients involved in the study.

A second more recent randomized trial with a control arm from China showed no benefit with the use of Hydroxychloroquine.⁴ Weaknesses of this trial include the study size which was 30 patients, and that the control arm also had other experimental treatments for COVID-19 including multiple anti-viral agents.

So why is the world supply of Hydroxychloroquine under strain? With a pandemic comes fear and the fear itself has caused even the most measured of us to regress to our survival instincts and hence hydroxychloroquine that until recently was a niche drug that was used primarily in autoimmune diseases is now hard to find and in high demand. The question is still open on whether Hydroxychloroquine has a clinical benefit in the treatment of COVID-19, but thankfully the answer will be forthcoming. Several clinical trials have been started to assess its effect on the treatment and prophylaxis against COVID-19. Here is a link to just one of the many clinical trials being initiated in the US. This trial is being initiated at Columbia University in New York and concentrates on prophylaxis for family members of COVID-19 positive patients. In first week of April, FDA issued Emergency use authorization (EUA) of hydroxychloroquine sulfate to treat hospitalised adults with COVID-19 when participation in clinical trial is not feasible.

Until the science is in, it is important to remember that Hydroxychloroquine and Chloroquine can have some side effects. They can cause retinal toxicity with prolonged use (greater than 5 years at 200 mg twice daily) and can cause heart arrhythmias (QT prolongation) with high doses or in susceptible people. 

REFERENCES: 

1. Al-Bari MAA. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol Res Perspect. 2017 Jan 23; 5(1).

2. Xue J, Moyer A, Peng B, et. al. Chloroquine is a Zinc Ionophore. Plos One. 2014 Oct 1;9(10).

3. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and Azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20:105949.

4. Chen J, Liu D, Liu P, et. al. A pilot study of hydroxychloroquine in the treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang University. 2020 Mar: 10.3785.