Coronavirus and Chloroquine?

Recently, one non-peer-reviewed publication claimed that a combination of hydroxychloroquine and azithromycin might be effective for treating the novel Coronavirus or Covid-19[1].

Hydroxychloroquine is a derivative of chloroquine, a common antimalarial drug. It is also used to treat amoebic liver abscesses when other drugs used for such infections are not working. These drugs also mildly suppress the immune system, which is why they are used as part of the treatment of some autoimmune disorders, such as lupus erythematosis or rheumatoid arthritis. It’s been known that chloroquine has some antiviral activity against certain viruses.

One thing that should be understood is that these are not entirely benign drugs. They have a number of side effects and adverse reactions. In addition to more mild side effects, such as nausea, headache, loss of appetite, and diarrhea, there are two more severe potential side effects. One is that long term use of these drugs can damage the retina and lead to macular degeneration, which is why patients taking these drugs long term need regular ophthalmological examinations. They can also affect the heart.

Another concern was that it is easy to overdose on hydroxychloroqine, its therapeutic window (the difference between the lowest effective dose and doses that will cause toxicity, in this case cardiac toxicity) being narrow. 

The other drug in the combination, azithromycin is a common antibiotic, used to treat a number of infections. It can also be used to treat malaria. It has few adverse side effects, but it shares one with hydroxychloroquine: it affects the heart. The FDA issued a warning in 2013 that azithromycine “can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.”

The study by Gautret et al. regarding the effect of hydroxychloroquine and azithromycin on coronavirus is not a randomized study and had only 36 patients. There is no evidence from this paper that these two drugs made any difference in the clinical outcomes of these patients.

This paper almost certainly would have failed peer review, given that it is not randomized, doesn’t do a proper intention-to-treat analysis, and has a whole lot of missing datapoints among the control subjects.

So, could hydroxychloroquine and chloroquine be effective drugs to treat and/or prevent coronavirus? It is a possiblity. There exists a plausible mechanism by which the drugs could inhibit viral replication, plus in vitro evidence of antiviral activity.

[Update 08 April 2020] Swedish hospitals abandon trial of promising malaria drug chloroquine for coronavirus patients after it caused them blinding headaches, vision loss and agonising cramps. See here.

[1] Gautret et al: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial in [not officially published] - 2020. See here (pdf).