The Rationale for Using Hydroxychloroquine and Azithromycin to Treat COVID-19


This is the first of a two-part Straight, No Chaser view at the rationales for and against using hydroxychloroquine and azithromycin to treat COVID-19.

Perhaps the distraction of the US President trumpeting (no pun intended) this combination has turned some away from the possibility that these medicines could be helpful. Maybe the well-publicized deaths of individuals taking the medicine has caused concern. Perhaps the robust criticism of the most-commonly cited study used as evidence has led many in the medical and scientific communities to be dismissive. Still, there has to be scientific reasons for putting forth the medications and the combination, right? In fact, there are.

Hydroxychloroquine and Azithromycin

Let’s review the ways the drugs work and the scientific rationale for their use against COVID-19.


Hydroxychloroquine (HC) is a derivative of an older drug (chloroquine). Both drugs are best known as drugs used to treat malaria, which is a disease caused by a parasite spread by mosquitos. HC has the following properties as a drug:

  • It disrupts the ability of parasites to reproduce and proliferate by blocking a chemical needed to digest proteins. It’s basically starving the parasites. This mechanism doesn’t appear to have applicability in viruses.
  • Even though HC is not an anti-viral medication, it has effects that could combat the way viruses in general replicate, thus slowing its spread.
  • There is evidence that HC inhibits cells’ ability to secrete substances known as cytokines. This is relevant because one of the most devastating effects of COVID-19 isn’t found in the activity of the virus itself. It’s the immune system’s response to the virus. In severe cases, there’s an overreaction by the immune system within the lungs by these cytokines. This by itself can cause fatal damage. This concept should be familiar to those with autoimmune diseases. Sometimes the body is just so exuberant in attacking foreign agents within us that damage occurs to us in that fight. Therefore, if HC activity blocked that cytokine release process, it conceivably would be helpful.
  • COVID-19 appears to bind to hemoglobin, the molecule that transports oxygen. COVID-19 seems to force hemoglobin to release its oxygen molecule. This reduces oxygen-carrying capacity, which ultimately contributes to feelings of shortness of breath. Most importantly, the lack of oxygen within the body’s cells contributes to their death. Furthermore, that unbound iron is a free radical and oxidant. In this state, it causes damage to lung cells (wanting to avoid this process is why so many of you take “anti-oxidants”). Hydroxychloroquine appears to inhibit the binding of COVID-19 to hemoglobin, theoretically reducing much of this.


Azithromycin is an antibiotic, meaning it is used against bacteria. You likely have taken it and know it as a “Z-pack.” It does not work against viruses. However, there are many situations in which a viral infection lowers the body’s immunity, and bacterial infections take advantage of the situation and “jump” on you. These are called secondary bacterial infections or co-infections. In these situations, azithromycin could be of use because it’s treating the secondary infection.

The Combination

There is actual case history for the use of hydroxychloroquine with and without azithromycin. It is used in China, South Korea and a few other countries. In fact China asserts that chloroquine might improve the overall treatment’s success rate and subsequent outcome, along with shortening hospital stays. Also, there are scattered physicians in the US who have (in)famously cited miraculous success using these drugs.


Many of those in the pro-camp for the use of these drugs also cite various studies that have shown promise for the use of these medicines. However, as we’ll discuss in the next Straight, No Chaser, those studies actually are support against the current use of these medicines. However, one recalls that penicillin was discovered on a mold that was stopping bacteria from growing on a petri dish.

Even with the theoretical benefits of these drugs having nothing to do with direct anti-viral properties, the indirect efforts are sufficient to suggest that robust research should be conducted within the medical tradition to establish if and how these medicines may be used in patients with COVID-19. It is not inappropriately hopeful to think hydrochloroquine could have a role in the more severe patients. Its indirect effects may prove to be a means of slowing down the march of COVID-19. It is most correct to say that there is insufficient evidence to advance its use, either as prophylaxis or treatment. It is equally important to note that all such evidence is either theoretical or anecdotal.

To that end, in late March, the WHO announced that hydroxychloroquine was among four treatments being analyzed as possible tools in this fight. There is a lot more to come and to be said.

The next post reviews the case against the use of hydrochloroquine and azithromycin in patients with COVID-19.

Need Masks?

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