
French researcher posts successful Covid-19 chloroquine drug trial - jseliger
https://www.connexionfrance.com/French-news/French-researcher-in-Marseille-posts-successful-Covid-19-coronavirus-drug-trial-results
======
hprotagonist
I have some meta-doubts about the linked presentation
([https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj...](https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub))

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...](https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-2-69),
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](https://twitter.com/JamesTodaroMD)
[1]: [https://www.riganollc.com/attorneys/gregory-j-
rigano/](https://www.riganollc.com/attorneys/gregory-j-rigano/)

~~~
avip
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...](https://sci-
hub.si/https://www.sciencedirect.com/science/article/pii/S0166354220301145)

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

------
ucha
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...](https://www.youtube.com/watch?v=n4J8kydOvbc&feature=emb_title)

pre-pub paper:
[https://www.sciencedirect.com/science/article/pii/S092485792...](https://www.sciencedirect.com/science/article/pii/S0924857920300820?via%3Dihub)

ppt (last page is result of experiment mentioned above):
[https://www.mediterranee-infection.com/wp-
content/uploads/20...](https://www.mediterranee-infection.com/wp-
content/uploads/2020/03/COVID-19.pdf)

~~~
aazaa
> 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.

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

------
tim333
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.

------
aazaa
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...](https://www.mediterranee-infection.com/coronavirus-
diagnostiquons-et-traitons-premiers-resultats-pour-la-chloroquine/)

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.

~~~
bertil
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.

~~~
greatpatton
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...](https://www.lemonde.fr/sciences/article/2020/03/17/la-chloroquine-
une-piste-pour-lutter-contre-le-sars-cov-2_6033364_1650684.html)

Are you highly skeptical of Le Monde?

~~~
bertil
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.

------
sheighzam
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...

------
Gatsky
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.

------
ck2
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](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](https://www.goodrx.com/hydroxychloroquine)

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

------
shanxS
From the article

Paper:
[https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj...](https://docs.google.com/document/d/e/2PACX-1vTi-g18ftNZUMRAj2SwRPodtscFio7bJ7GdNgbJAGbdfF67WuRJB3ZsidgpidB2eocFHAVjIL-7deJ7/pub)

Video(not in English): [https://www.mediterranee-infection.com/coronavirus-
diagnosti...](https://www.mediterranee-infection.com/coronavirus-
diagnostiquons-et-traitons-premiers-resultats-pour-la-chloroquine/)

~~~
bertil
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.

~~~
cm2187
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...](https://www.ncbi.nlm.nih.gov/pubmed?term=\(Raoult%2C%20Didier%5BAuthor%5D\)%20AND%20%22lancet%22%5BJournal%5D)

[2]
[https://www.ncbi.nlm.nih.gov/pubmed?term=(Raoult%2C%20Didier...](https://www.ncbi.nlm.nih.gov/pubmed?term=\(Raoult%2C%20Didier%5BAuthor%5D\)%20AND%20%22The%20New%20England%20journal%20of%20medicine%22%5BJournal%5D)

~~~
bertil
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.

~~~
j88439h84
I don't think 'controversial' is the right word for "he’s happy to say things
that will make some people unhappy."

------
CaveShadow
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...](https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWSHnGbj/view)

~~~
Nettle2
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!

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

~~~
raindeer3
Form what I read the UK has already stopped all export of this drug.

~~~
77pt77
This is easy to synthesize and very cheap.

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

~~~
stubish
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.

------
DoreenMichele
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

------
sheighzam
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...

------
ncmncm
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.

~~~
Nettle2
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.

------
mrob
>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.

~~~
bertil
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.

~~~
jaclaz
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](https://news.ycombinator.com/item?id=22616404)

------
tim333
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...](https://www.mediterranee-infection.com/wp-
content/uploads/2020/03/COVID-19.pdf) (graph at bottom)

------
oli5679
Naive question, does this mean quinine may also help, and is there enough in
tonic water to have any clinical effect?

~~~
dheera
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.

~~~
nullc
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?

------
ineedasername
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.

~~~
ncmncm
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.

------
nraynaud
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.

------
jeromebaek
Explains why there's little outbreak in Africa.

~~~
tim333
Probably not. It's available there but it's not like everyone is on the stuff.

------
sheighzam
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!

------
theologic
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.

~~~
avip
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).

~~~
sgt101
Is it unapproved? I thought it was in widespread use as an anti-malarial (for
70 + years)?

~~~
77pt77
It is widespread but this usage is off label.

------
fhoe
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.

~~~
cm2187
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).

------
Ace17
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.

