Are Hydroxychloroquine and Azithromycin Effective Against COVID-19?

Dr. Didier Raoult, French physician and microbiologist who thinks he has an effective treatment for COVID-19 (click for image source)
Two weeks ago I wrote about a possible treatment for COVID-19, the pandemic disease that is affecting most of our lives. It has been championed by French physician and microbiologist Dr. Didier Raoult. So far, he has written two papers about it (here and here). I was excited about his initial report, and I was hoping for a serious follow-up study. When I saw that he had written a second paper, I eagerly read it. Unfortunately, it wasn’t the serious study that I had hoped for. Nevertheless, it has gotten some media attention and seems to have influenced the FDA, so I decided to share my thoughts on it.

The results seem very exciting. He and his colleagues treated 80 patients with the malaria-fighting drug hydroxychloroquine and the antibiotic azithromycin. They note that they saw “clinical improvement” in 78 of them. One of the other two (an 86 year-old patient) died, and the other (a 74 year-old patient) was still in intensive care when the paper was written. While that sounds really good, there are a couple of “red flags” that make me hesitant to think that the treatment is as effective as it seems.

The first problem is that there is no control group. In a serious medical study, there needs to be a similar group of patents who do not receive the treatment. The treated group can be then measured against the untreated (control) group. Without that, it is very difficult to determine what the actual effect of the treatment is. Of course, I understand why there is no control group. Dr. Raoult wants to save lives. He thinks his treatment is effective, so he wants to give it to as many people as he can. He would have to “withhold” his life-saving treatment from some people so that he could have a control group, and that could lead to more deaths. I can understand why a physician would shudder at that idea.

However, the control group is important, because we really have no idea what would have happened to the 78 people who recovered had they not been given the treatment. While we still don’t know, the fatality rate of this disease is thought to be 1-2%. In 80 people, then, you would expect only one or two (0.8-1.6 to be precise) deaths, so this group of patients has the fatality outcome we expect had there been no treatment at all.

Now, of course, Dr. Raoult and his colleagues did more than just track whether or not the patients died. They tracked the amount of virus in each patient’s nasal cavity and found that the amount of virus dropped significantly for most of them. Once again, that sounds nice, but without a control group, we simply don’t know whether or not that was because of the treatment.

The second problem is the profile of patients who got the treatment. They mostly seemed to have a mild case of the disease. Only 15% had fever. Only 53% showed signs of lower respiratory tract infection. Worse, 5% showed no symptoms at all. Once again, it isn’t surprising that most of these patients recovered – most of them fit the profile of people who are expected to recover.

There is a third problem. A scientific study has been done in China with a control group. It is very small, and I can’t read it, since it is in Chinese. However, based on a Forbes article, the study had 30 patients. Half were given hydroxychloroquine, and half were not. That study showed no significant difference between the control group and the treatment group. Thus, if that study is correct, hydroxychloroquine is not an effective treatment for COVID-19.

Now, of course, that study didn’t include the antibiotic, so it’s possible that Dr. Raoult’s treatment is better than the treatment assessed by the study. It’s also possible that because of problems with the Chinese study’s design (small number of patients and no placebo, for example), the Chinese study is wrong. From a scientific point of view, then, we simply do not know whether or not Dr. Raoult’s treatment (or hydroxychloroquine by itself) is effective against COVID-19.

Nevertheless, the FDA has approved using hydroxychloroquine and other, similar drugs to treat COVID-19. This is probably a good plan, since the risks of using the drugs are low. However, until serious, controlled studies are done, we have no idea whether or not they are doing any good.

16 thoughts on “Are Hydroxychloroquine and Azithromycin Effective Against COVID-19?”

  1. Compare that to the 2.7% fatality rates in China or the 1.7% rates in the US. The best one could hope to say from these results is they followed the Hippocratic oath, “I will use treatment to help the sick according to my ability and judgment, but never with a view to injury and wrong-doing. Neither will I administer a poison to anybody when asked to do so, nor will I suggest such a course.”

  2. There is a Jewish doctor in N.Y. touting this as well. The article says he has used it successfully on 500 people and on a recent YouTube video he now says it’s well over 600 people.

    In another interview of a religious activist I follow, he says he was given the drug in combination with an HIV drug. This is apparently the protocol in Austria. He said he noticed a change almost immediately and is now on the road to recovery.

    1. I am glad that people are getting better, but once again, without a control group, have no idea whether or not it is because of the treatment. Also, I am very skeptical of any treatment that claims it is 100% effective. Medicine rarely works like that.

    1. As I told John, I am VERY skeptical of any claim that a medical procedure is 100% effective. Medicine doesn’t work like that. Once again, without a controlled study, we have no idea whether or not the treatment actually did anything.

  3. 100 percent IS a pretty weighty claim. I guess we’ll have to wait and see what more thorough trials ultimately reveal.

    I’m still watching Denmark and Sweden. I think you might disagree but it seems like it’s the closest thing we have to a control group on strict quarantine vs a scaled back (but still very open) society.

    Obviously we can’t know all the variables but these two countries are socially and ethnically very similar and also geographically close, so it’ll be useful to see if the full lockdown measures made a significant difference (exponential difference).

  4. I previously wrote with a lot of confidence that chloroquine should be used. All my reasons were good then and still good now.

    One of the things that seems glaringly missing is an analysis of why the virus has been controlled both in China (if you believe their stats) and in S. Korea. And why has the USA vaulted to the top of the charts in terms of number of cases and are #3 (at the moment) in the number of deaths? Merely because of testing? I have to doubt that. We were way down on the hit parade 3 or 4 weeks ago and now we’re #1? The virus continues to be on an exponential increase here. Why have we shot past every other country?

    In this country there’s been foot dragging and resistance to everything that could help except shutting down the economy, the thing which, political effects aside, is going to really hurt a lot of Christian ministries not to mention hurting the country as a whole. I’m very concerned about the AIG and ICR ministries who have a lot invested in tourist attractions which are now shut down. Meanwhile there’s a strong 5th column influence saying not to blame or suspect China, our 2nd biggest enemy. (The first is our spiritual enemy.) China, who has put a lid on the virus is not being effected while we’re dealing with a monstrous monkey wrench in the gears!

    1. The U.S. has jumped to the top of the charts because of our large population. I think this graph is the best one to compare countries:

      China isn’t on there, because their numbers are almost certainly false, only France and South Korea have done a better job in limiting the death rate. This might change, of course, but for right now, the U.S. is looking pretty good.

        1. I meant France. Look at the graph I posted in that reply. It shows deaths per million people by the number of days after the first reported death. France’s curve doesn’t go up for the longest number of days, compared to the other countries, and its number of deaths per million people is consistently the lowest compared to the other countries (except South Korea) for each day past the first death. To me, that means they are managing the crisis the best (except for South Korea, which started off poorly but seems to be doing the best now).

        2. But according to the BBC link I posted above, France is not counting COVID deaths that happen in nursing homes. Simply not counting deaths is an easy way to flatten the curve.

        3. I was just telling you why I meant France. Certainly, if they aren’t counting deaths properly, then that conclusion is wrong.

        4. Okay, I get where you are coming from now. I just had never heard anyone say that France was doing well before and I have been getting pretty far into the weeds on this topic. Your chart is pretty cool, but sadly, I have come to the conclusion that the only data that is worth anything comes from a few narrow studies of things like Cruise ships or isolated Italian towns that have been studied in detail. Everything else (even a lot of US data) has so much ambiguity in it to be almost worthless.

  5. Hey Dr. Wile,

    I wanted to share a little of my research. In college my virology professors really directed much of the study in courses to antiviral targets. Having a good understanding of all the biochemicals at play provide possible targets to stop the virus. The main identifier would be a chemical a human cell doesn’t use but is critical for viral replication like viral polymerase and reverse transcriptases.

    To keep it simple, the spike is important on many levels but mainly for getting into the cell. The reactions involving the spike appear to be acid-induced which allow the virus to bind to the cell and get dumped into the cytoplasm. Hydroxychloroquine appears to increase the ph of these intracellular vacuoles. Next, the antibiotic was interesting but not too shocking because many doctors prescribe an antibiotic to flu infections just in case it may be a bacterial infection or to prevent a coinfection. All I could really find on it as it relates to antiviral properties was a study in 2010 that showed in bronchial tissue azithromycin prevented mRNA translation. It seemed only to have those properties in bronchial tissue which would make it a nice fight against a virus being able to make its proteins.

    So together they appear to attack cellular recognition and viral replication.

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