# Hydroxychloroquine, an Idea that Could Kill People

**URL:** <https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098>\
**Category:** Conversation\
**Tags:** Science\
**Created:** [April 7, 2020, 4:39pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098 "2020-04-07T16:39:50Z")\
**Posts on this page:** 16\
**Page:** 1

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [April 7, 2020, 4:39pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/1 "2020-04-07T16:39:50Z")

</div>

[https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6](https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6)

Regarding that horrible COVID-19 study ([A Really Bad Clinical Study on COVID-19](https://discourse.peacefulscience.org/t/a-really-bad-clinical-study-on-covid-19/10009)):

> So while this is a small study and not a perfect match, it provides no evidence to show that the HCQ/AZ combination had any benefit at all.

But going on…

> While we’re on the subject of QT prolongation, there’s [this preprint](https://www.medrxiv.org/content/10.1101/2020.04.02.20047050v1.full.pdf) from a medical team at NYU that was also treating patients with the same combination of drugs. In 84 patients, they found notable QT prolongation in about 30% of them, and another 11% were to a level (\>500 milliseconds) that put them at a high risk for arrhythmia. This group’s mean age was 63, 74% male. No

> But with that in mind, the authors report what looks like a bad interaction in that species between HCQ and metformin. And by “bad”, I mean about 30% mortality. If this translates at all to humans, it could be bad news, because (as mentioned above) diabetics look like a high-risk group and many patients may well have been taking metformin when they present at the hospital.

> It’s weird and startling, though, if you haven’t had the opportunity to go back through clinical research (and even patient treatment) and seen how many things looked like they worked and really didn’t. It happens again and again. Alzheimer’s drugs, obesity drugs, cardiovascular drugs, osteoporosis drugs: over and over there have been what looked like positive results that evaporated on closer inspection. After you’ve experienced this a few times, you take the lesson to heart that the only way to be sure about these things is to run sufficiently powered controlled trials. No short cuts, no gut feelings – just data.

---

<div class="post-metadata">

**Author:** ![Mercer](https://avatars.discourse-cdn.com/v4/letter/m/e274bd/32.png) [@Mercer](https://discourse.peacefulscience.org/u/Mercer)\
**Post date:** [April 7, 2020, 4:44pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/2 "2020-04-07T16:44:08Z")

</div>

> [@A Really Bad Clinical Study on COVID-19](https://discourse.peacefulscience.org/t/a-really-bad-clinical-study-on-covid-19/10009/71):
>
> I had the malaria medication at the ready, but did not use them as a prophylactic as prescribed. No one at the mine did because of side effects from long term use.

IMO doxycycline is a better bet than the malaria prophylactics that make you crazy.

> [@A Really Bad Clinical Study on COVID-19](https://discourse.peacefulscience.org/t/a-really-bad-clinical-study-on-covid-19/10009/72):
>
> Pretty clear evidence that chloroquine isn’t a magic superdrug for this virus. Beyond that . . . they’re small studies, and one is uncontrolled. More data needed.

Yes, and given the number of physicians trying it, the bias against publishing negative results, and our incredible ability to fool ourselves, at this point absence of evidence strongly indicates evidence of absence.

At this point, we have to keep in mind that 1 of every 20 studies that is properly done will find a therapeutic effect with a p of 0.05, so we can be statistically certain that such studies will be published.

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [April 7, 2020, 4:44pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/3 "2020-04-07T16:44:56Z")

</div>

From the OP’s article…

> One more point: someone last night was trying to tell me that my job was to “bring people hope” and that my attitude wasn’t helping with that task. Let me clear that up. I am not a physician, and I am not a clinician. I have spent my career in very early stage drug discovery, not at the bedside. Unfortunately, my lab skills are not well matched to the current epidemic – my own research has been more oncology-focused, and it’s way back in the pipeline. None of the last three companies I’ve worked for currently have any antiviral research. So as for my contribution to fighting the coronavirus, well, you’re looking a significant part of it right now. I can curate and annotate the news, add my own opinions after thirty years of drug discovery work and (I hope) make people smarter about what’s going on.
> 
> But keep in mind, most of what I’ve done, the great vast majority of what I’ve done over that thirty years has not worked in the clinic. _Most things don’t_ . My job as a researcher has not to been to raise people’s hopes without data in hand, my job has been to try to produce such data so as to raise hopes with some reason to do so. When I see something to be hopeful about, I’ll say so, and when I think people are getting ahead of what we know, I’ll say that, too. Go back to the [first things I wrote](https://blogs.sciencemag.org/pipeline/archives/2020/03/19/coronavirus-some-clinical-trial-data) about the hydroxychloroquine/azithromycin work: I called it “potentially very interesting” and called for more data to see if it was real. That’s where I still am. Raising hopes just for the sake of raising hopes is not where I am, though, and in fact I find that whole idea to be cruel. We’re going to defeat this virus, this epidemic, by being as hard-nosed as we can be about collecting real data on real-world outcomes as quickly as efficiently as we can, not by talking vaguely about miracle cures and isn’t it something and wouldn’t it be great. You’ll need to go somewhere else for that. Try Dr. Oz, he’s good at that crap. I’ll stick to what I’m good at here.

---

<div class="post-metadata">

**Author:** ![Art](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/art/32/3805_2.png) [@Art](https://discourse.peacefulscience.org/u/Art)\
**Post date:** [April 7, 2020, 6:52pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/4 "2020-04-07T18:52:54Z")

</div>

Zinc was mentioned before in the discussion of hydroxychloroquine:

> **[LA doctor: COVID-19 patients go from 'very ill' to 'symptom-free' in 8 to 12...](https://www.theblaze.com/news/la-doctor-hydroxychloroquine-zinc-coronavirus)**
>
> 'Clinically, I am seeing a resolution'

Again, anecdotes don’t cut it, but the theme of targeting viral RNA replication is a common one in the different trials that have been ongoing or being started. I believe both remdesivir and Actemra are nucleoside analogs of sorts. This harkens back to the first drug (as far as I can recall) used to treat AIDs - AZT.

---

<div class="post-metadata">

**Author:** ![AllenWitmerMiller](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/allenwitmermiller/32/2519_2.png) [@AllenWitmerMiller](https://discourse.peacefulscience.org/u/AllenWitmerMiller)\
**Post date:** [April 7, 2020, 8:53pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/5 "2020-04-07T20:53:27Z")

</div>

> [@Art](#):
>
> Again, anecdotes don’t cut it

Yes. And the Blaze has always been my favorite peer-reviewed medical journal. Not. (I almost used an emoticon but successfully resisted!)

That Blaze article includes this important offer: “Ditch the fake news ==\> Click here to get news you can trust sent right to your inbox. It’s free!”

Irony abounds. (Of course, the reporting of what an actual doctor says about his actual opinion is not necessarily “fake news” per se—but you get the idea. Anecdotal accounts turned into reports that get people all excited, including some White House people, is not good.)

---

<div class="post-metadata">

**Author:** ![Mercer](https://avatars.discourse-cdn.com/v4/letter/m/e274bd/32.png) [@Mercer](https://discourse.peacefulscience.org/u/Mercer)\
**Post date:** [April 7, 2020, 9:45pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/6 "2020-04-07T21:45:31Z")

</div>

> [@swamidass](#):
>
> Regarding that horrible COVID-19 study ([A Really Bad Clinical Study on COVID-19](https://discourse.peacefulscience.org/t/a-really-bad-clinical-study-on-covid-19/10009)):
> 
> > So while this is a small study and not a perfect match, it provides no evidence to show that the HCQ/AZ combination had any benefit at all.

The journal is disavowing it now:

> **[Statement on IJAA paper | International Society of Antimicrobial Chemotherapy](https://www.isac.world/news-and-publications/official-isac-statement)**
>
> Statement on IJAA paper | International Society of Antimicrobial Chemotherapy

I also learned something new and scary from the comments on the _Science_ blog:

_Hydroxychloroquine has a half life of 50 days, meaning it resides in the body for nearly a full year. If you react poorly to it, you are screwed._

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [April 7, 2020, 11:54pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/7 "2020-04-07T23:54:36Z")

</div>

I think that is because there is evidence it conjugates to proteins in red blood cells, which take quite a while to clear. If there is a bad reaction however, they might clear quicker. It would be good to see some references on this.

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [April 7, 2020, 11:55pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/8 "2020-04-07T23:55:42Z")

</div>

This is a good time to note that @nlents and I are interviewing a drug development expert next week in livestream. Details to follow.

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [April 8, 2020, 4:57pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/9 "2020-04-08T16:57:14Z")

</div>

3 posts were split to a new topic: [High Throughput Screening for New Drugs?](https://discourse.peacefulscience.org/t/high-throughput-screening-for-new-drugs/10108)

---

<div class="post-metadata">

**Author:** ![glipsnort](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/glipsnort/32/1541_2.png) [@glipsnort](https://discourse.peacefulscience.org/u/glipsnort)\
**Post date:** [April 8, 2020, 7:17pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/11 "2020-04-08T19:17:55Z")

</div>

There’s one possibility that I haven’t seen mentioned: CQ or HCQ could actually make COVID-19 worse. At least that’s what CQ seems to have done with chikungunya in an animal study.

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [February 21, 2021, 1:19am UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/12 "2021-02-21T01:19:21Z")

</div>

61 posts were split to a new topic: [Comments on Bad Hydroxycloroquine Study](https://discourse.peacefulscience.org/t/comments-on-bad-hydroxycloroquine-study/13240)

---

<div class="post-metadata">

**Author:** ![Mercer](https://avatars.discourse-cdn.com/v4/letter/m/e274bd/32.png) [@Mercer](https://discourse.peacefulscience.org/u/Mercer)\
**Post date:** [April 8, 2020, 8:15pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/15 "2020-04-08T20:15:39Z")

</div>

Just noting that the _Science_ blog @swamidass cited is superb:

> **[In the Pipeline](https://blogs.sciencemag.org/pipeline/)**
>
> Derek Lowe’s commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine.

---

<div class="post-metadata">

**Author:** ![Mercer](https://avatars.discourse-cdn.com/v4/letter/m/e274bd/32.png) [@Mercer](https://discourse.peacefulscience.org/u/Mercer)\
**Post date:** [February 20, 2021, 1:22am UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/63 "2021-02-20T01:22:14Z")

</div>

We now have a very good idea why hydroxychloroquine doesn’t work in people, despite my friend’s 2005 paper showing that it worked beautifully to stop SARS-CoV-1 in cultured cells. Both SARS-CoV-1 and SARS-CoV-2 use a second pathway for getting into cells that is insensitive to hydroxychloroquine; moreover, that pathway is more important for SARS-CoV-2. This was conclusively demonstrated by swapping the relevant parts of the spike protein:

> **[Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by...](https://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1009212)**
>
> Author summary The novel pathogenic coronavirus SARS-CoV-2 causes COVID-19 and remains a threat to global public health. Chloroquine and hydroxychloroquine have been shown to prevent viral infection in cell-culture systems, but human clinical trials...

Hydroxychloroquine might still have some utility as an adjunct in combination with inhibiting TMPRSS2 protease, but this explains all of its clinical failures, @Giltil and @colewd.

Once again, science is more dependable than wishful thinking.

---

<div class="post-metadata">

**Author:** ![Witchdoc](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/witchdoc/32/10610_2.png) [@Witchdoc](https://discourse.peacefulscience.org/u/Witchdoc)\
**Post date:** [February 20, 2021, 7:46pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/65 "2021-02-20T19:46:50Z")

</div>

In terms of mechanism of action, it is still not known all that well how hydroxychloroquine works (both as anti-malarial and anti-rheumatic), though we use it in rheumatoid arthritis and lupus.

I’m glad you’re not a doctor. A possible mechanism of benefit does not overrule RCTs testing whether or not the drug is beneficial in a given scenario.

Btw, “HCL” looks more like hydrochloric acid than hydroxychloroquine.

> - The initial study that showed its benefit wasn’t well controlled and randomised.  
> [Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial - PMC](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102549)
> - [The anti-inflammatory drug hydroxychloroquine does not significantly reduce admission to intensive care or death in patients hospitalised with pneumonia due to covid-19, finds a study from France published by The BMJ today.](https://amp.reddit.com/r/science/comments/gk67gr/the_antiinflammatory_drug_hydroxychloroquine_does/)
> - [The malaria drug hydroxychloroquine did not help prevent people who had been exposed to others with Covid-19 from developing the disease, according to the results. Slightly over 40% of people who took hydroxychloroquine experienced side effects, although none were serious.](https://amp.reddit.com/r/science/comments/gwg2qo/the_malaria_drug_hydroxychloroquine_did_not_help/)
> - [Hydroxychloroquine, with or without Azithromycin in Mild-to-Moderate Covid-19, did not improve clinical status at 15 days as compared with standard care. | NEJM](https://amp.reddit.com/r/science/comments/i03d3a/hydroxychloroquine_with_or_without_azithromycin/)
> - [The combination of hydroxychloroquine and azithromycin significantly increased mortality in COVID-19 patients (relative risk=1.27), finds a new systematic review and meta-analysis. (Clinical Microbiology and Infection Journal, 26 August 2020)](https://amp.reddit.com/r/science/comments/ihy7lq/the_combination_of_hydroxychloroquine_and/)
> - [There was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19.](https://amp.reddit.com/r/science/comments/j3lek1/there_was_no_clinical_benefit_of/)

> Two large randomized clinical trials ([RECOVERY](https://www.recoverytrial.net/) and [SOLIDARITY](https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments)) have both reported no benefit and potential risk from hydroxychloroquine. Derek Lowe has good summaries of both on his _Science: In The Pipeline_ blog: [The RECOVERY Trial Reports on Hydroxychloroquine](https://blogs.sciencemag.org/pipeline/archives/2020/06/05/the-recovery-trial-reports-on-hydroxychloroquine), [The SOLIDARITY Data](https://blogs.sciencemag.org/pipeline/archives/2020/10/16/the-solidarity-data). A combination of the two trials with 27 smaller randomized trials found no benefit from the drug (RR=1.10, 0.99-1.22). Due to the lack of efficacy and potential risk, both RECOVERY and SOLIDARITY have discontinued the hydroxychloroquine arms of their trials.

[https://amp.reddit.com/r/science/comments/jr84fn/study\_hydroxychloroquine\_no\_better\_than\_placebo/](https://amp.reddit.com/r/science/comments/jr84fn/study_hydroxychloroquine_no_better_than_placebo/)

---

<div class="post-metadata">

**Author:** ![Mercer](https://avatars.discourse-cdn.com/v4/letter/m/e274bd/32.png) [@Mercer](https://discourse.peacefulscience.org/u/Mercer)\
**Post date:** [February 20, 2021, 8:22pm UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/67 "2021-02-20T20:22:55Z")

</div>

> [@Witchdoc](#):
>
> In terms of mechanism of action, it is still not known all that well how hydroxychloroquine works (both as anti-malarial and anti-rheumatic), though we use it in rheumatoid arthritis and lupus.

Correct, but it’s fairly clear that for coronaviruses, it changes endosomal and lysosomal pH.

---

<div class="post-metadata">

**Author:** ![swamidass](https://sea2.discourse-cdn.com/flex016/user_avatar/discourse.peacefulscience.org/swamidass/32/3_2.png) [@swamidass](https://discourse.peacefulscience.org/u/swamidass)\
**Post date:** [February 21, 2021, 1:19am UTC](https://discourse.peacefulscience.org/t/hydroxychloroquine-an-idea-that-could-kill-people/10098/68 "2021-02-21T01:19:33Z")

</div>