Social media is one again a-twitter (pun intended) over hydroxychloroquine as a supposed COVID-19 therapy that is (for some reason) being suppressed by a variety of evil actors: physicians, Big Pharma, Anthony Fauci, etc.

This is a modest effort to explain why these arguments don’t make sense, or are misleading.

I’ve already discussed the fact that all randomized controlled trials have shown no benefit form hydroxychloroquine in COVID-19. This includes treatment, post-exposure prophylaxis, and prevention.

Randomized controlled trials are the gold standard of medicine. When you have lots of them about a treatment that says the treatment doesn’t work, that’s a pretty good sign something is unsuccessful; or if it does provide benefit it’s so small as to not be worth worrying about.

Other types of trials and studies are not as good. There are too many ways to skew the data–for example, if you pick who you give medication to and who gets placebo instead of doing it randomly, you may bias the results.

A few studies keep getting cited as supposed “evidence” that there is a cover-up.

2005 – Journal of Virology

The first is a study from the Journal of Virology. It is dated 2005 — fifteen years ago. This is an eternity in medicine.

COVID-19 did not exist when this study was done. The study was done on SARS (which is related to COVID-19 but is not the same thing).

More importantly, however, is that this study is in vitro. That is Latin for “in glass”–it means it is a study on cells in a petri dish–in this case, tissue culture of monkey KIDNEY cells (i.e., not even lungs).

(People have usually heard of couples with fertility problems having “in vitro” fertilization or IVF–that’s a test tube baby. The egg and sperm are fertilized “in glass” in the lab, and then implanted into the mother’s uterus. So, if you like, this study has as much to do with COVID-19 in living humans as making a test tube baby has to do with real human sexual intercourse, i.e., nothing.)

In vitro is where you start research, it’s where you look for promising leads. But there’s a huge distance between in vitro and human use (in vivo = in life). In vitro gives you ideas to test further, but most of them don’t pan out in real life.

My favourite example of this principle is bleach killing bacteria–if you have bacteria in vitro (a test tube) and you add bleach, you will kill them. It works really, really well.

But, that doesn’t mean that you can drink or inject bleach into a human patient, and have it kill their bacterial infection. (Well, I guess it would kill them eventually since it would kill the patient and then the bacteria wouldn’t have anything to eat and they’d eventually die too, but killing the patient is generally considered a side effect that isn’t desired.)So, this study is:

  • 1) Not about COVID-19
  • 2) Not in real life, it’s in a test tube
  • 3) Not a randomized controlled trial
  • 4) The idea was tested multiple times in real humans with real COVID-19 in clinical trials and it didn’t work. This is disappointing, but usually how it goes.
  • 5) In kidney cells, not even lung cells.

There is a 2020 study that is also in vitro that does use COVID-19. It too works in tissue culture. So, anyone who is citing the 2005 study to you doesn’t know what they are talking about, because it is:

  • a) fifteen years old;
  • b) talking about a different virus when we have a study of the virus we care about in 2020;

So, if in vitro work proved anything, they should be citing the 2020 study. But most are just parroting each other, not understanding the study at all.

If we wanted to save lung cells in tissue culture in a dish, hydroxychloroquine would be awesome. But we want to save human lives. Not the same thing. The tissue culture told us it would be good to look at it, and people have. And it didn’t work. That’s the way the ball bounces in medical research. Most promising things don’t pan out.

Henry Ford Center Observational Trial

This is a more recent trial, and it is in humans (in vivo) and it involves COVID-19. So it is already way better than the 2005 example above.

But it is what is called a “retrospective observational trial”:

Limitations to our analysis include the retrospective, non-randomized, non-blinded study design.

It does not involve randomization. It basically just takes a bunch of patients after the fact, gets all the charts together, looks at what people did, and sees what the results were.

In this case, patients who got hydroxychloroquine did better than those who didn’t. So, case closed, right? Well, not so fast.

The problem is, as it happened, most of the patients who got hydroxychloroquine also got steroids.

Steroids are often used in these types of cases, because it is partly the body’s inflammatory response that causes the damage. So, steroids help the body from being too “enthusiastic.” This works for lots of diseases, and so it makes sense to see if it works for COVID-19.

A randomized controlled trial DOES show that steroids help. They are now a standard part of recommended COVID-19 treatment for those who need oxygen.

This is good news, but it creates a problem for the Henry Ford observations. If I give a drug that works (steroids) and a drug that doesn’t work (hydroxychloroquine) to people, and they get better, is it fair to say that BOTH drugs work? No, that’s silly.

If you know steroids work, you can’t combine them with hydroxychloroquine and compare them to patients who didn’t get either drug, and then claim that hydroxychloroquine works.

What you’d need to do is give EVERYONE who qualifies for steroids the steroid, and then give hydroxychloroquine to half and placebo to the other half. But that hasn’t been done by Henry Ford. And when we give hydroxychloroquine, death rates don’t change.

The study authors are quite clear that this is not some sort of slam dunk. They are being responsible scientists and clinicians; those who are using this study in a political way are not:

our results should be interpreted with some caution and should not be applied to patients treated outside of hospital settings. Our results also require further confirmation in prospective, randomized controlled trials that rigorously evaluate the safety and efficacy of hydroxychloroquine therapy for COVID-19 in hospitalized patients

How about Zinc?

What about needing to add zinc to hydroxychloroquine for it to work? Sorry, that too has been looked at in a trial of nearly a 1000 people, and it made no difference. More work is on-going, but for now there’s just no evidence it helps.

Lots of other agents have also been looked at, lots of which are cheap. These include ACE inhibitors, statins, ARBs, NSAIDs, azithromycin (an antibiotic). So far, none have helped.

Why not use it? What can it hurt?

Hydroxychloroquine has a number of potential heart side effects that can cause death. The risk of those side effects increases with more medications being used, and many of these patients have a number of other illnesses (“comorbidities” we call them) that involve the heart and other drugs.

Using hydroxychloroquine could increase death rates. That’s unacceptable for a drug with no proven benefit, and considerable evidence that it does not work.

Also, there are patients that do need hydroxychloroquine. Using the med for COVID-19 denies the medication to those who do need it. (There are supply issues.) I had patients early in the pandemic who were having a hard time finding their medication, until the Alberta College of Pharmacists clamped down on dispensing hydroxychloroquine for unproven and untested uses.

It’s not fair to harm some patients who need a medication that we know works, just so people for whom it doesn’t work can have it.

The supposed conspiracy

Some are claiming that doctors or big pharma or whoever don’t want hydroxychloroquine to work, because it is cheap or generic, or whatever.

This doesn’t make much sense. Doctors don’t get paid more if we use more expensive drugs (or any drug at all). (And, doctors are more likely to get sick than most people–so they have no interest in hiding things that work.)

But, most importantly, perhaps–remember, we ARE using steroids. They are recommended and now standard treatment.

But guess what? Steroids are cheap –they are generic drugs, they’ve been around for years, and no one has a patent on them either. Just like hydroxychloroquine.

So, if this is some big conspiracy, why are we happy to use steroids, but not using hydroxychloroquine except in clinical trials?

The reason is simple–because one works, and the other doesn’t. If the data changes, that will change.

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