French researcher posts successful Covid-19 chloroquine drug trial | Hacker News Reader

French researcher posts successful Covid-19 chloroquine drug trial

connexionfrance.com

219 pointsjseliger112 comments

I have some meta-doubts about the linked presentation (https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj...)

1. for starters, it's a random gdrive link not on medrxiv or biorxiv. why?

2. it's GPL3'd? Conventionally, we disseminate open access research as CC-BY 4.

3. the first author is who he says he is -- but he is a "managing partner" at blocktown capital not a practicing physician. [0]

4. The second author is a bioinformatics masters student who is also a lawyer and not obviously a practicing researcher. [1]

5. Figures 1 and 2 are presented without obvious attribution from https://virologyj.biomedcentral.com/articles/10.1186/1743-42..., which is not about SARS-CoV-2, but about the first SARS from 2002.

This isn't my field, but i am a biomedical researcher and i'm very used to reading the medical literature, and this read deeply strangely in a lot of ways that are hard to quantify. The language isn't what I'd expect for a research paper, but it's kind of written like it wants to be one. I'm not super clear on what's going on.

I have no reason to doubt the intentions of the authors, per se, but this work is super rough around the edges. It reads like a thrown-together collection of notes for a lab meeting, but not something I'd show off in public.

[0]: https://twitter.com/JamesTodaroMD [1]: https://www.riganollc.com/attorneys/gregory-j-rigano/

I'm generally in agreement with you, but tangentially, Chloroquine was already tried in some countries (not in the controlled sense we expect in an actual clinical trial), and showed "promising results"

https://sci-hub.si/https://www.sciencedirect.com/science/art...

that is a much more comprehensibly written document. Nice find.

it might be that this author is rushing to confirm something that other research is already suggesting. south korea and italy are both using hydroxychloroquinine at scale and US hospitals are also starting to use it.

> italy are both using hydroxychloroquinine

Do you have a link? I wonder because the "regular" media does not talk about it, and the AIFA (Italy's FDA) did not make public statements on the use of this drug.

The UK blocked the export of Chloroquinine on Feb 24th without much fanfair. I believe they don't want regular people rushing out to hoard the drug when they don't need it. There is already lots of talk on Twitter about shortages for people who were already using it (ie, for Lupus).

In Canada it requires a prescription but plenty of countries have it over-the-counter.

There are some news about a limited trial on 15 people:

https://www.fondazioneveronesi.it/magazine/articoli/lesperto...

but of course that is old news, 13 th March.

It mentions "Chinese patients" which means that at least generally, cloroquine is not yet used here (Italy) as an accepted/attempted therapeutic protocol (although I'm sure it was used for compassionate use).

Toclizumab is a different story, since there's now a proper trial with 300 patients starting on Thursday.

Guidelines from the Italian Society of Infective Diseases Physicians indicates chloroquinine/hydroxychloroquinine as a first line treatment together with one of various antivirals.

http://www.simit.org/medias/1569-covid19-vademecum-13-03-202...

Thanks a lot.

I know MedCram has covered the use of hydroxychloroquine a few days ago (at 1:20): https://youtu.be/vE4_LsftNKM?t=79

More on chloroquine & zinc: https://youtu.be/U7F1cnWup9M?t=95

He is an active ICU specialist MD out of CA and makes some of the only expert videos on the subject at the moment.

I listened to the linked video and read the article/papers. What I take from them is:

- Chinese doctors initially tested chloroquine in-vitro on SARS-Cov-2 and it reduced the viral load significantly. Similar results were observed with other viruses including SARS-Cov.

- They then tested it in-vivo (on patients) and it showed promising results

- The speaker explains then that they had 3 cohorts of infected patients on which they tested daily for SARS-Cov-2. First cohort was the control (no treatment), second one received Plaquenil (hydroxychloroquine), third one received Plaquenil and azithromycin (an antibiotic). After 7 days 1st cohort had approximately 85% testing positive, 2nd 40%, 3rd 5%. One could be surprised by the use of an antibiotic but it apparently helps with fight opportunistic bacterial infection resulting from a viral pneumonia. He adds that for every recorded death, the patient tested positive for the virus before their death and concludes that if the double treatment of azythromicin + Plaquenil reduces the viral load, then it would improve patient prognosis.

In conclusion, I think it's quite a big deal if it is confirmed that chloroquine can reduce contagiosity and improve outcomes. It's widely available, cheap and safe. Give it to everyone showing symptoms, individuals who were in contact with confirmed cases, medical professionals, and you'll surely reduce R0 significantly.

video: https://www.youtube.com/watch?v=n4J8kydOvbc&feature=emb_titl...

pre-pub paper: https://www.sciencedirect.com/science/article/pii/S092485792...

ppt (last page is result of experiment mentioned above): https://www.mediterranee-infection.com/wp-content/uploads/20...

> last page is result of experiment mentioned above

The last slide is a bibliography. The second to the last is a slide is in vitro results.

There's not one shred of new clinical data in that presentation from what I can see.

What's happened is that the OP has linked to an article making claims that are not supported from the slide deck or YouTube video.

You're mistaken. The last slide is, like I said, the result of the experiment, the second to last is the bibliography.

Only for the record, not only Chinese, the idea dates back to the previous SARS (Italian but not that bad in Google Translate):

https://www.iss.it/web/guest/primo-piano/-/asset_publisher/o...

Good to see some progress. The more experimental research on this sort of stuff the better. It's still not clear if these sort of meds should be given early as soon as you get a temperature say, or wait till hospital, or how those options compare. I'm hoping there'll be some good result like giving it early means almost everyone recovers without hospital but then maybe that won't work. Test baby test!

In fact this sort of stuff may be our biggest hope. Containment doesn't seem to be working, vaccines will likely take too long but treatments like say giving chloroquine on fever might reduce deaths from 1% to 0.1% or some such. But we won't know without experiment.

Call me skeptical.

The details in this article are insufficient to draw many conclusions. There is no paper, although a YouTube video (in French) is linked. The article doesn't make it clear whether Raoult was being interviewed, or the information was taken from the video.

The linked Google Doc (not regarding the study in question, despite another comment on this thread) summarizes results from other purported studies. Even then, this document itself appears to lack the usual signs of authenticity.

Be careful about drawing conclusions because the details just aren't there. Details are everything in drug discovery.

Edit:

Then there's the vague language in the article.

> “We were able to ascertain that patients who had not received Plaquenil (the drug containing hydroxychloroquine) were still contagious after six days, but of those that had received Plaquenil, after six days, only 25% were still contagious.”

"Contagious" means nothing because AFAIK, there is no test for it. There is a PCR test being used around the world to detect the presence of viral RNA. So it's suspicious that an expert would be using the word "contagious," which implies the ability to transmit the virus under experimental conditions.

And it gets worse.

Have a look at the video linked in the article:

https://www.mediterranee-infection.com/coronavirus-diagnosti...

First, it begins with a title that doesn't match the title of the speaker's slide deck.

Second, judging from the slides the video appears to be about COVID-19 testing in general. There doesn't seem to be anything of substance about chloroquine anywhere. I don't speak French, so maybe there is something there. If so, the slide deck doesn't reflect it. And there's no way that a successful clinical trial of a COVID-19 drug would begin with basic introductory slides that everyone already knows.

This just doesn't add up. I'm calling bullshit.

The article links to that research too: https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj...

Under: "US academic study concurs" half page.

I have never heard of that news source, Connexion France. The language is all over the place. I’d be highly skeptical of that source. The hospital quoted isn’t one of the main institute that would have a direct mandate from the government: Institut Pasteur (in spite of being private) would the reference research center for infectious diseases.

The domain appears to have been registered in 2004.

They state they've been around since 2002: https://www.connexionfrance.com/About-Us-Legal-Information

That page doesn’t really look like most reasonable media ‘About Us’ page: no by-line, no photos, link to PO boxes or AWS (!), unclear editorial line. I’m happy there is a (generic) name for the editor but the rest wouldn’t really count as a positive to me.

It'd be easier if you pointed out what about their site set you off into thinking it was fake news conspiracy pushing publication...

Institut Pasteur is not the only research body in France regarding infectious diseases... They are directly linked to the Marseille University Hospital (AP-HM) and all the usual public research bodies like INSERM, CNRS.

If you want another source than connexion France, you have this article from Le Monde: https://www.lemonde.fr/sciences/article/2020/03/17/la-chloro...

Are you highly skeptical of Le Monde?

I would be skeptical of _Le Monde_ too indeed. My point was that particular site had all the flavours of the fake news site that had mushroomed in the last year, with non-sensical translations and controversial content.

Before anyone raids pharmacies, I’d rather have a vigorous debate with peers, clear methodology, etc.

Previous thread on the Chinese study https://news.ycombinator.com/item?id=22601196

This is the presentation Raoult gave yesterday, publication is coming next week. https://youtu.be/n4J8kydOvbc Link to the powerpoint. Please don't kill the IHU's servers though: it's all in french. https://www.mediterranee-infection.com/wp-content/uploads/20...

1. The video is linked in the article.

2. The linked PDF is just a generic presentation about COVID-19 testing.

I believe the 6th and last slides are the result of their own testing and experiments.

I think you have to watch the video to understand why he is going through other published results on that virus. I understand he is pushing the idea that instead of telling people who feel sick to self isolate and only call a hospital (and get tested) if they have respiratory problems, to instead test them early, and if the are positive, provide them with anti-viral treatments. That way the patient is contagious for less than a week instead of 3 weeks on average.

> I understand he is pushing the idea that instead of telling people who feel sick to self isolate and only call a hospital (and get tested) if they have respiratory problems, to instead test them early, and if the are positive, provide them with anti-viral treatments.

If so, that's about as far away from reporting the results of a successful clinical trial as you can get.

The article is fake.

Any doctors or medical researchers here? I am not, so DON'T take the following as if I personally have any knowledge in this area. So talk to a medical expert about this!

A Chinese study from March 9, see the link 1) with a downloadable PDF, say the following in its conclusions: "Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro."

Does the French study use Hydroxychloroquine as well? From the article it mentions Hydroxychloroquine but also Chloroquine phosphate.

1) https://academic.oup.com/cid/advance-article/doi/10.1093/cid...

Didier is very real.

"According to the analysis of the publications from 2007 to 2013 ... Didier Raoult appears at the top of the European classification (including Israel) with 18,128 citations.... He totalizes more than 2,300 indexed publications..."

https://en.wikipedia.org/wiki/Didier_Raoult

Chloroquine is very real: This Feb 20, 2020 Nature>Cell Research paper mentions the efficacy of chlorquine: https://www.nature.com/articles/s41422-020-0282-0

Chloroquine is real, but in vitro work is a long, long way from human treatment. The paper you linked is an in vitro study only. There isn't even any preliminary animal data.

Just an FYI doctors are using hydroxychloroquine in the US today to fight C19.

This isn’t the only study that suggests chloroquine is a good treatment. Medcram had its own analysis of a different paper from china that said hydroxychloroquine was useful when administered early. However it’s possible new data may present itself in the coming weeks that suggest otherwise.

But the type of confirmation you’re looking for is impossible in this critical timeframe.

I wish I could find the study so take this with a grain of salt without my presenting that, but I'll do a search; it's also all in French. It was a double blind, peer reviewed, replicated study that suggested 400-500mg hydroxyquinone (NOT hydroxyquinone sulfate,nor chloroquine nor chloroquine phosphate) + azithromycin (Zithromax, Z-pack, etc.) + zinc was shown to be effective either once symptoms began to shorten the duration, or can be used as a prophylactic measure, preventing the disease altogether in medical personnel. Raoult was one of the scientists behind the study, which differed slightly from his other studies. There was has been a 100% success rate so far, and presently they are testing on a larger sample of those in the medical profession. I will try to find the link.

Very interesting stuff on this page that I'll have to read through...

The bottom line is there isn't any quality data. But there are a lot of clinical trials in patients going on, so there should be something more reliable in 4 weeks or so. The most relevant endpoint at this time is not viral clearance (which also has reliability issues), it is avoidance of severe disease requiring hospitalisation and respiratory support, in particular invasive ventilation. Also relevant is whether prophylactic treatment in people at high risk of infection, such as healthcare workers, is effective.

The treatment courses are short, so the side effects of hydroxychloroquine are largely irrelevant under the circumstances.

That's hydroxychloroquine right?

Same drug they use to treat lupus so it's well tested?

edit: oh wait, maybe not https://www.ncbi.nlm.nih.gov/pubmed/32150618

      Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

If so, goodrx shows it's $20, hopefully it will spare some deaths.

https://www.goodrx.com/hydroxychloroquine

No, it is a relative to the drug. Although from what I understand is that they behave similarly. Someone posted a link to this useful video yesterday, https://www.youtube.com/watch?v=U7F1cnWup9M

edit: typo

Chloroquine is a common anti-malarial and can be purchased OTC in much of Latin America.

From the article

Paper: https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj...

Video(not in English): https://www.mediterranee-infection.com/coronavirus-diagnosti...

That researcher is likely, at best, controversial:

- he starts by arguing against quarantine; his point is that it didn’t work for Cholera in 1832;

- he dismisses two thirds of the efforts against HIV/AIDS: understanding transmission effort and promoting condoms, focusing on treatment lowering viral load;

- he then moves on to framing response to the pandemic in a conspiracy-sounding “shift of power towards the Far East”;

- he then says “most countries” have chosen to test extensively early — I don’t think that’s really true: South Korea, has but I don’t think many other did;

- he’s surprisingly unmoved by mortality on the cruise boat ashore Japan; I know epidemiologists can seem comfortable with terrifying stats, but he’s more than that.

He’s not terrible over all and fairly eloquent to make his case but I’d take his presentation with a grain of salt.

Key points:

- children don’t seem to be contagious (they are asymptomatic but vectors for the flu);

- viral loads are more predictive than anything;

- people appear contagious for 20 days; key point isn’t a fix duration but measuring viral load and isolating anyone with a high level;

- the hospital has 143 samples, they are looking forward to comparing genes with symptoms.

He’s happy that people are attacking him for advertising chloroquinine because the controversy drives traffic… Not sure most doctors would be confortable with that media strategy. He’s unhappy that television features people without qualification, though.

He compares his findings with similar findings in China and Korea with slightly different treatment (600 mg vs 2x500 hydroxi-chloroquinine, which he claims to have been the first to propose for other infections).

He uses patients from nearby town who didn’t receive the treatment in a quasi-experiment on the impact on viral-load duration. He’s also recommending a combination with an anti-biotic because complications are often microbial.

His final point is to not recommend to go home but be tested and treated.

I think that he’s onto something scientifically and he could be talking about it on TV but before that, he _needs_ to get some media training to focus on the positive.

One one point, HIV treatments is so effective now (viral load undetectable) that many don't use condoms with informed partners. On the other end of the spectrum PrEP has been wildly successful in virtually eliminating transmission. And we know humans are not great at using condoms despite the risks.

The focus on the viral load has helped, that’s for sure but as doctor and a researcher, I wouldn‘t throw most of the initial effort under the bus, or explain that quarantine doesn‘t work by quoting a pre-Pasteur example.

does higher viral load mean worse symptoms?

He seems to assume it but doesn’t really detail. I’m not sure there’s a scale for measure symptoms in details.

question about viral load[0]: do masks reduce it ?

[0] IIUC viral load means amount of viruses getting in your system

I believe that viral load ("charge virale") is the number of virus in your system, so mainly viruses that are coming out of your own cells. Masks prevent contamination before it starts but if one is measuring load, I’d say it’s too late.

ok, I thought it was the initial intake

Is that what you base him being "controversial" on? My understanding is that he regularly publishes in the Lancet [1] and New England Journal of Medecine [2] (if I am using pubmed correctly).

[1] https://www.ncbi.nlm.nih.gov/pubmed?term=(Raoult%2C%20Didier...

[2] https://www.ncbi.nlm.nih.gov/pubmed?term=(Raoult%2C%20Didier...

His tone is controversial: he’s happy to say things that will make some people unhappy.

You are quoting a highly respected peer-review journal. Those were set-up to avoid appeals to individual authority and replace them with (anonymous) peer review. His presentation is certainly promising but it hasn’t gone through such a review yet.

I don't think 'controversial' is the right word for "he’s happy to say things that will make some people unhappy."

How does his tone compare to other French researchers? The work is the important bit, not the accent or even individual personality.

He wrote letters to the editor of the Lancet in response to somebody else's papers!

That researcher is probably one of the best experts on communicable diseases with decades of experience : http://www.expertscape.com/ex/communicable+diseases

He has published at least 71 articles : http://www.expertscape.com/ar/communicable+diseases/a/Raoult...

His most recent article seems to be "Chloroquine and hydroxychloroquine as available weapons to fight COVID-19" https://www.ncbi.nlm.nih.gov/pubmed/32145363

Have you already published something in this domain ? Is it your field of expertise ?

I have not but she has: https://twitter.com/MicrobiomDigest/status/12414295448478638...

I don't see how any of what he's saying can be interpreted as controversial and I think you're nitpicking. I watched his presentation and to me he is clearly suggesting we move to a treatment based approach _after_ finding something that works, while suggesting that we can do better than we did with cholera and aids - medical professionals didn't even want to test their patients.

And obviously nothing coming out now is going to be clinical trial grade research! At least you admit that he's onto something, so it's strange to see you up and down this thread criticizing his work and presentation.

He’s not asking for reviews, or using the usual precautionary tone: he’s claiming that his solution work, explicitly seeking limelight. I’m afraid of two things:

1. Without professionals pandemic specialist to deliver the message, people who care about rumours, organisation and industrial capacity, there will be runs on pharmacies and hospitals won’t be able to treat severe patients in time. Or that people start taking large amount of a fairly toxic compound. Or that people leave quarantine because they have taken an (unproven) treatment. The 200,000 people who have seen this video, how many know how to measure a viral load? How many will decide to order Chloroquine vs. have the lab experience to measure that? Chloroquine is available OTC in many countries because most people take it as a prophylactic. Can you guarantee that the same people won’t double the dose, to an amount that even Pr. Raoult sees as hard to manage? There’s already been some problematic situations with masks.

2. Other doctors in this pandemic or the next, admire his success, stumble on a treatment that has similar numbers but isn’t a solution (because of confounding factors, lack of random control trial) publish it through the same channels.

I’m not a clinician, but I teach people how to use proper scientific method and avoid listening to the loudest voice in the room, even when that voice is right, because science was built on giving time to the less appealing criticism.

I’m not criticising his work: he’s onto something. I am criticising his presentation because he’s explicitly ignoring good practices.

I think he just wants to get this out there and in use by people. It's a fairly harmless drug that can even be taken long term (so long as you don't start hallucinating -- I have) and there are long term effects on respiratory capacity from this infection in some people who might otherwise be healthy.

But I completely agree though that once we're through this, we need proper clinical trials. And people are going to be stupid and overdose or break quarantine and all that stuff...but there's not much you can do about that: https://www.youtube.com/watch?v=ZZamrmTMs6w

Better to have that stuff out there than not, though honestly I think we're going to end up having to have a forced quarantine like China, because whatever we're doing now may not end up working.

I don’t know what he wanted, but he walked into creating this aware, awake and knowing:

https://twitter.com/BostonJoan/status/1240626380020289539

I'd love to have your reaction to this: https://twitter.com/MicrobiomDigest/status/12414295448478638...

This is some good research...reading it now.

Fox news, bitcoin..the communities surrounding these two entities are cesspools of misinformation and do pose a risk that I don't believe should be abated by throwing away the idea of abridged trials during times like these.

Look, my brother is infected, and he's positive and under 40 without any underlying disease and weeks of respiratory symptoms. Doctors now think he might suffer permanent lung damage in the form of reduced lung capacity, so on a personal/emotional level, the risk of doing nothing is far greater than any side effects such a dose could bring.

On the other hand, we have people still going out for spring break and crowding the parks in Florida and NYC respectively...and a drug with this effect might close the gap between a proper lockdown and whatever it is we have going on now. With those two risk factors in mind, I think it's fair to let this half-assed study out into the wild. It's not like chloroquine is available without a prescription, and people will be vomiting their guts out from the sugar long before they get a clinical dose of it from tonic water.

But come to think of it...did the author of the original paper go on Tucker Carlson and say that it's 100% effective or was that the random eye doctor? If it's the former, then yea I'm furious, but I can't seem to find the clip. Otherwise, stuff like this is never going to stop from happening. It sounds to me like the real culprits here are the news agencies responsible for diluting down the information responsibly.

> did the author of the original paper go on Tucker Carlson and say that it's 100% effective

He did so, in French but he absolutely offered to go on the French talk shows, with a clear snide to Cauhet, the French equivalent of Tucker Carlson, because people who were not him where scaring people into quarantine while he “has a treatment that cheap, reliable and safe”. So yes, he absolutely did that.

There was no reason to make his presentation public beyond specialists — hell, he quotes studies on the same molecule who have shared temporary results without the same publicity.

Found the clip. That doctor is insane.

And a short presentation:

https://www.mediterranee-infection.com/wp-content/uploads/20...

See the last slide, combination with Azythromycin seems to help (they say). Azythromycin is the widely known Zithromax, less than 7€ to get a box of 500mg doses.

Interesting. Zithromax is an antibacterial, not an antiviral.

New Paper just released by the same group: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open- label non-randomized clinical trial Gregory Rigano @RiganoESQ (posted to twitter 7am PDT 3/18/2020 Didier Raoult MD, PhD

https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWS...

Gregory Rigano ist a LAWYER who is trying to get a patent for Hydroxychloroquinine as Covid-19 treatment. This must be a complete fraud! Obviously someone with high fever during the infection will have his temperature lowered, since this is also the purpose of the drug during a malaria attack! Even if there is a real effect in vitro, if it doesn't work in vivo, it means nothing! The medical world is littered with unsuccessful in vivo attempts of in vitro successes!

This sounds really promising! I hope this report find its way to the officials...

Form what I read the UK has already stopped all export of this drug.

Yes, alongside Aletra.

Source: https://www.pharmaceutical-technology.com/comment/parallel-e...

This is easy to synthesize and very cheap.

It also has potentially irreversible side effects, namely retina damage.

Thankfully retina damage seems to only be from continual use. This is medication people have stayed on for decades. It seems pretty benign for just a few weeks, unlike many medications where the long term side effects can kick in after just months.

I can readily believe this is helpful. It's related to quinine. I've used quinine for years to deal effectively with exposure to viral infections.

I have a compromised immune system and get sick very easily. I do a lot of weird stuff.

/Anecdata

I'm curious about the Tocilizumab/Actemra study, but it's extremely dangerous to the heart, so I'm interested in the dosages and time frame used

Also curious about the Remdesivir studies...

I can't say whether the work reported is defensible, but I can say that (1) chloroquine is not available over the counter in the US as it is in many places, (2) it can be dangerous, even fatal if misused, and (3) it is available in the US in pet stores for treating aquariums.

So, provided you only put it in the tank you swim in, you should be OK, but I don't know about the safety of chloroquine phosphate taken orally. Still, if you are on the down slide, it might be preferable to risk it, and also to have some on hand against such an event.

Hydroxychloroquinine is the drug that my father received during World WarII to treat Malaria tropica. The high dose worked so well on him, that he never again had a malaria attack. But unfortunately he developed severe liver damage as a consequence of the high dose, from which he never completely recovered.

>Patients were given 600mcg per day for 10 days.

Did they really mean micrograms or is this a mistranslation of milligrams? 600mcg is much lower than any dose I've heard of for other conditions.

I'm sure it's mg. There is a similar experiment from Melbourne that cites similar dosage. I'll try to find it.

Also, it looks like there is a US clinical trial of chloriquine to start in May: https://clinicaltrials.gov/ct2/show/NCT04303507

EDIT: this source [0] seems to confirm that it is indeed milligrams, but I don't understand how any of this jives with what I found earlier from the FDA on therapeutic index and overdosing.

[0]: https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj...

See the original comment with my findings from the FDA below, however.

---

I don't think it's a mistake. 600mg per day is 14x the recommended dosage for malarial suppression with cholorquine.

Per the FDA, the dosage is 300mg of chloroquine per week for malarial suppression:

> Adult Dose: 500 mg (=300 mg base) on exactly the same day of each week.

For children:

> The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

Source: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/00...

Additionally, it seems that it is incredibly easy to fatally overdose on this:

> Chloroquine is very rapidly and completely absorbed after ingestion. Toxic doses of chloroquine can be fatal. As little as 1 g may be fatal in children. Toxic symptoms can occur within minutes. These consist of headache, drowsiness, visual disturbances, nausea and vomiting, cardiovascular collapse, shock and convulsions followed by sudden and early respiratory and cardiac arrest. Hypokalemia has been observed with arrhythmias in cases of intoxication. The electrocardiogram may reveal atrial standstill, nodal rhythm, prolonged intraventricular conduction time, and progressive bradycardia leading to ventricular fibrillation and/or arrest. Cases of extrapyramidal disorders have also been reported in the context of chloroquine overdose (see WARNINGS and ADVERSE REACTIONS)

See also this paper about known cases of overdose in kids: https://pediatrics.aappublications.org/content/27/1/95.long?...

Note that is for all for cholorquine base, not chloroquine phosphate which is ~60% choloroquine.

In the video he says that his hospital and Korea use 600 mg/d and that Chinese authors mention two times 500 mg per day. He describes that larger treatment as “harder to handle” and I suspect he’s referring to secondary effects.

The tests suggested in Italy also use a 500 mg per day dose, see article linked to here:

https://news.ycombinator.com/item?id=22616404

Summary of the best bit:

Viral load dropped to near zero in patients with azithromycin and hydroxychloroquine compared to not much change with the control group https://www.mediterranee-infection.com/wp-content/uploads/20... (graph at bottom)

Naive question, does this mean quinine may also help, and is there enough in tonic water to have any clinical effect?

1. Yes. 2. No, you'd have to drink like 30 liters a day.

No. 1 liter of commercial tonic water has about 83 mg of quinine, and the typical dose for malaria treatment is 648 mg three times a day. You'd have to drink 23.4 liters of tonic water a day to get that amount of quinine, and you'd probably poison yourself from that amount of water and sugar.

These doses are quite high though because they are using them for treatment.

Preventative doses of chloroquine for malaria are about 300mg per week. I'm not sure what preventative doses of quinine are typically, presumably much higher than chloroquine, but how much higher?

I wonder if quinine, a very similar drug, would have similar results. We already have industrial infrastructure in place to mass produce and disseminate quinine (tonic water) but would have to increase the amount in each bottle. Pure, unadulterated speculation though.

Quinine has much worse side effects than chloroquine's. The amount of quinine in tonic water is very, very low, or it would not be allowed.

Fun fact: the lifetime of chloroquine in the body is 1 to 2 months.

I saw a tweet by a MD recently saying that some preliminary explanation of the effect of the virus (something about heme) would also explain why chloroquine would work.

There seem to be a web of low quality data going in a coherent direction.

Explains why there's little outbreak in Africa.

Now that's an interesting theory...

Probably not. It's available there but it's not like everyone is on the stuff.

No. Temperature has more to do with it, which has already been proven with the semi-log growth charts.

Studies show that hydroxychloroquinone- not chloroquine or chloroquine phosphate - is what's effective. It has less side effects if not used for a long period of time (>5 years, then serious liver and retinal damage can occur). Plaquenil, the brand, is 100% hydroxychloroquine (possibly hydroxychloroquinone sulfate, I'd have to check), which requires perfect dosing per patient, usually around 500mg/day for a typical adult.

With the generic hydroxychloroquinone, there are fillers, so taking 600mg might be better off, but don't quote me.

The problem is that hydroxyc. can have major interactions with antibiotics (which interests me, since Azithromycin is recommended in conjunction - perhaps its referring to Flouroquonines which are very dangerous to cartilage anyway by themselves (Levaquin,Cipro,etc.). Also, seizure meds psychiatric meds, acetaminophen, and blood pressure medicines can cause interactions.

Hydroxychloroquinone can actually help with weight loss and lowering glucose levels.

I think this sounds promising - not as a treatment per se, nor a vaccine, but a prophylactic at the first sign of symptoms. I suspect adding zinc might be helpful, but that's just my idea for clearing up infections sooner.

I think the Azithromycin may be used to address any bacterial side effects to which the hydroxychloroquinone may leave the immune system more susceptible, such as eye problems and strep. Another reason I think early use of zinc may help.

Anyway, this is interesting stuff. And it's so cheap - since it's already a generic, no "lawyer" can patent this to make money.

I think they're just trying to find the treatment, and I'm grateful it's not big pharma!

I am tremendously torn by this:

a. We have multiple indications that this is an adjunct therapy that can help

b. Humans are exceptionally easy to fool, and we know that placebos are incredibly effective because they trick our brain into creating chemicals.

The placebo is so strong that we design double blind studies because we can't even trust the person giving the experiment.

However, if it does help, it will be extremely encouraging. The critical thing is to get a double blind study with sufficient n to immediately make a choice. This is where having more resources do help because the safety of the drug, normally a massive bottleneck, is well understood.

You're missing the point that patients receiving this treatment are considered in a terminal condition and are likely on life-support (that is the only situation you could give an unapproved drug to a patient).

Is it unapproved? I thought it was in widespread use as an anti-malarial (for 70 + years)?

It is widespread but this usage is off label.

This is not an unapproved drug, just an off-label use. From wikipedia:

> Chloroquine was discovered in 1934 by Hans Andersag.[3][4] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[5]

Where did you see that this is for terminal conditions? Raoult suggested even patients with mild symptoms be treated with those molecules to reduce the contagion.

If a placebo is actually effective against covid-19, what difference does it make that it's a placebo? It's still good news.

If you asked the patients if the felt better it could be placebo effect but I don't think any placebos drop measured viral load like that.

The problem is patients only get this at the point that they require hospitalization.

It should be as easy to get a short-term dose of this (unlikely to cause severe side effects) as it is to get a seasonal flu shot, and people should be advised to take it for two weeks (or whatever) at the onset of symptoms, or even as a prophylactic if they know they were exposed.

I don't think he was suggesting it as a preventive use. Rather as a way for patients that have been diagnosed with the virus, even with little symptoms, to make them less contagious quicker (and therefore to significantly slow down the propagation of the virus).

No placebo for the control group? no double-blind?

C'mon guys ... these kind of crisis are where strict scientific discipline is the most needed, because the risk of rushing to a false conclusion is higher.

"but we don't have time, so we'll take whatever that seems to work" would be a valid argument if Chloroquine had zero negative side-effects. Which isn't the case.

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