
Hydroxychloroquine Probably Isn’t the Answer - obituary_latte
https://www.acsh.org/news/2020/03/25/will-hydroxychloroquine-chloroquines-safer-cousin-make-coronavirus-cut-14663
======
ucha
This morning we had:

France ex-IHU Marseille/AP-HP: 79160 cases, 7527 dead, mortality rate 9.5%

IHU Marseille/AP-HP: 3005 cases, 33 dead, mortality rate 1.1%

France doesn't use HCQ consistently yet. Didier Raoult who heads the IHU in
Marseille has been using it systematically on all cases, even mild ones for
more than 2 weeks. I doubt such a difference in mortality rate could be
explained by a difference in number of tests performed or other parameters.

Everyone can have all sorts of opinions on the efficacy of the treatment but
in the end, mortality rates don't lie. And no, differences in the level of
care, health or other smaller factors cannot explain an 8x difference.

In addition to that, most patients seem to have elevated ferritin which would
be a side effect of consuming too much iron. In this case, it is theorized
that when the virus replicates, it creates non-essential proteins that take
place of the iron in hemoglobin thus preventing red blood cell from carrying
O2 and CO2 from and back to the lungs. Based on molecular simulations, it
seems that HCQ can bond to those viral proteins preventing them from expelling
iron from hemoglobin. It would also explain why it's useful to treat someone
early on rather than later when their hemoglobin lost their iron... Source
here:
[https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surf...](https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173)

~~~
rrss
Seems like those statistics would be pretty easily explained by Marseille
being a week or two behind other areas in France on the epidemic curve.

Pennsylvania: 11510 cases, 150 deaths, mortality rate 1.3%

Is Pennsylvania also using HCQ systematically on all cases? I don't think
these crude CFRs are useful.

~~~
ucha
That's the most interesting rebuttal I've heard but I don't think it's true.
Everything else being equal, you could estimate the stage of the epidemic by
the number of cases per capita. The Marseille department, Bouches-du-Rhône,
has 3% of the French population and about 4% of cases.

Also, in your example, the crude CFR for the US is 2.9% right now, so only
2.2x that of Pennsylvania. We're talking about 8+ here.

~~~
rrss
You didn't finish the comparison for cases for capita.

Bouches-du-Rhône has ~3% of the French population and ~4% of the covid-19
hospitalizations.

The department of Paris has ~3% of the French population and ~10% of the
hospitalizations.

That seems to indicate that Bouches-du-Rhône is behind Paris.

(used hospitalizations instead of cases only because I couldn't find a good
source for case breakdown by department. numbers from
[https://dashboard.covid19.data.gouv.fr/](https://dashboard.covid19.data.gouv.fr/))

------
logicbombr
Prevent Senior in Brazil, an health operator with mosts of its patients on
risk groups (60+ yo) are using hydroxychloroquine on all its COVID-19 patients
with tremendous success.

Right now I choose to believe on MD in front line rather then in Health
Societies, FDA, WHO and those bureaucrats who let the virus spread all around
due to its incompetence

~~~
jacquesm
Do you have a reference for this?

~~~
andrenth
This local news article (in Portuguese) has quotes from Prevent Senior
executives:
[https://www.diariodaregiao.com.br/_conteudo/2020/04/cidades/...](https://www.diariodaregiao.com.br/_conteudo/2020/04/cidades/saude/1190185-medicos-
relatam-sucesso-no-uso-da-hidroxicloroquina-em-pacientes-com-covid-19.html)

“Every patient showing symptoms and with CTs indicating the presence of
Covid-19 are invited to join the protocol. We’ve discharged more than 200
patients”.

------
tgafpc2
This site also has an article wistfully praising Remdesivir, a proprietary
drug with far less evidence than HCQ. I think money might be talking here.

~~~
cjhopman
A proprietary drug whose maker has said they will donate all 1.5 million doses
that they currently have. That's more than they'll be able to produce over the
next year (1 million) even after greatly increasing that production capacity.

~~~
pseudalopex
The goal is more than 1 million treatment courses (10 million doses) by the
end of this year.

[https://www.gilead.com/stories/articles/an-update-on-
covid-1...](https://www.gilead.com/stories/articles/an-update-on-
covid-19-from-our-chairman-and-ceo)

~~~
cjhopman
Ah, I had misread that.

That statement didn't clearly say whether they were going to donate those that
they haven't produced yet. If they aren't donating that, this donation is like
a ~10% discount (compared to the ~66% discount I had originally interpreted it
in that case).

------
snapetom
“ There is absolutely no evidence that HCQ or HCQ/azithromycin would have any
effect on seriously ill patients with viral pneumonia.”

Correct. that’s against the thought right now. HCQ is great at preventing
patients from getting to the serious pneumonia stage. Once they’re on a vent,
they should be on another cocktail.

~~~
jojo2000
Yes, once they're on a vent, your main problem is not even the viral load, but
rather that the body reacts to the infection in desperate ways like cytokine
storm [0] which destroys organs.

[0]
[https://en.wikipedia.org/wiki/Cytokine_release_syndrome](https://en.wikipedia.org/wiki/Cytokine_release_syndrome)

------
gonational
Has anyone noticed that the CDC’s reported deaths by week from ordinary flu
and pneumonia have been plummeting while COVID-19 death rise?

They are down from the normal 4.5k+ per week during this period to around 2.3k
per week and they are falling parabolically as COVID-19 expands.

What could cause this?

~~~
mjul
The Danish Serum Institute runs a “sentinel” testing programme for the common
flu, and they note in their report about covid-19 last week (available in
Danish) that the common flu has mostly been eliminated since the social
distancing and lockdown measure were implemented. They interpret this a
leading indicator for the reduction in covid-19 since it has a similar
transmission mechanism.

~~~
foota
Would be amazing if we managed to eliminate the common flu as a side effect of
this :) not likely, but it does seem possible?

~~~
obituary_latte
There’s an interesting docuseries on Netflix that is partially about a team
that is working on a permanent 1-shot flu vaccine:
[https://www.netflix.com/title/81026143](https://www.netflix.com/title/81026143)

------
ysleepy
If it would have situation altering effects we would already know. Huge
effects would have been seen very early in the wide spread application of it.

~~~
Ozzie_osman
I'm not so sure. Let's say it halves the number of deaths or halves the time
it takes for someone to get better. But also it requires a certain dose to be
most effective. How would you know in this fog of war? You'd still have many
patients who are sick or dying.

The whole point of this article is that it's really hard to know without
controlled, randomized trials. And I agree.

~~~
ysleepy
Sure, but more so than all the other drugs?

People just have a problem with a no-information-yet state, they'd rather talk
about the unfounded rumor than acknowledge that people are hard at work and
there is no definitive news yet.

------
ck2
It's more likely ivermectin, FDA/WHO approved, cheap, well tested on both
animals and humans and aggressive against covid19 in virto

[https://www.sciencedirect.com/science/article/pii/S016635422...](https://www.sciencedirect.com/science/article/pii/S0166354220302011)

[https://www.who.int/bulletin/volumes/82/8/editorial30804html...](https://www.who.int/bulletin/volumes/82/8/editorial30804html/en/)

every dog, cat and horse that is on heartworm medication is already using it

------
fareesh
I have G6PD deficiency and there are mixed opinions on whether this form of
chloroquine is safe for me to take. The deficiency affects about 400M people
worldwide, surprised to see that this part of the discussion rarely gets
brought up.

------
af33
> There is absolutely no evidence that HCQ or HCQ/azithromycin would have any
> effect on seriously ill patients with viral pneumonia

It's supposed to be taken BEFORE you become seriously ill and develop ARDS.

In fact, many elites are put on a short course of HCQ/Z-Pak as soon as they
show symptoms, even before the results of their tests come back (which can
take days).

> [https://www.cbsnews.com/news/coronavirus-treatment-drug-
> hydr...](https://www.cbsnews.com/news/coronavirus-treatment-drug-
> hydroxychloroquine-doctor-prescription-family-friends/)

------
podgaj
Can someone explain the dearth of research looking out how zinc deficiency
might explain variations in outcome after SARS-CoV-2 infection?

Both ADAM17, which helps ACE2 shed from the cell, and ACE2 itself, are zinc
finger proteins and use zinc as a cofactor.

------
PragmaticPulp
Collectively, we need to get over the idea of all-or-nothing solutions to
Coronavirus.

We're not going to wake up one day with a "cure" for COVID-19. No one in the
medical field actually expects Hydroxychloroquine to produce miraculous
recoveries at this point. The idea is that any treatment that slows the
progress of the infection will also buy the patient's immune system more time
to fight the infection. If we can push the peak symptoms back even 1-2 days
relative to untreated individuals, that gives the immune system that much
extra time to mount an effective defense against the virus.

When we finally confirm which treatments, if any, are useful for slowing the
progress of the infections, we can combine them with earlier testing and
identification to help reduce the number of patients who require
hospitalization. It won't look like a cure, but it will be making improvements
in treatment outcomes and reducing the burden on hospitals.

At this scale, a small modification of disease severity can still be useful
for minimizing the burden on hospitals, even if it doesn't fit the narrative
of a miracle cure.

~~~
gus_massa
> _The idea is that any treatment that slows the progress of the infection
> will also buy the patient 's immune system more time to fight the
> infection._

Is there any serious trial that shows that Hydroxychloroquine has any effect
at all?

~~~
Mountain_Skies
Double blind peer reviewed trials are a good goal but in the middle of a
crisis you can't let a desire for perfection get in the way of the good. There
is enough imperfect evidence that this treatment stack (that is, several drugs
used in combination with hydroxychloroquine) has benefits that it should be
considered a potential part of a solution. Waiting a couple of years for
perfect studies to be carefully conducted is waiting until the crisis is over
and the treatment moot. What is well known are the side effects of this drug,
their likelyhood, and how to ameliorate them.

~~~
gus_massa
> _There is enough imperfect evidence that this treatment stack_ [...] _has
> benefits that it should be considered a potential part of a solution._

Is there any evidence? Do you have a link to the best evidence so far? Did
someone tried a similar treatment and get the same result?

It is not necessary to have a perfect study, because there too little time.
But how hard is to make a study with a randomized control group? You are not
sure if this drug is better or worse, so giving only the standard treatment
perhaps is better. I guess a double blind experiment is more difficult for
logistic reasons, but if the patients have respirators and are sedated, it is
almost a single blind experiment. And if the results are the number of death
or an analysis in a lab by a machine (instead of self reports), they can be
less influenceable.

~~~
pbreit
Yes, there is quite a bit of evidence.

Proven against SARS in vitro:
[https://www.ncbi.nlm.nih.gov/pubmed/15351731](https://www.ncbi.nlm.nih.gov/pubmed/15351731)

And much evidence for efficacy against COVID-19 in humans:
[https://twitter.com/__ice9/status/1246549028382408706](https://twitter.com/__ice9/status/1246549028382408706)

------
swader999
From what I've read it only works when given very early in the illness.

------
stri8ed
Not to diminish the possible successes, but without a randomized control
trial, there is no way the success can reliably be attributed to the
medications.

That's not to say they should stop prescribing it, simply due to lack of
formal trials. But the perceived benefits should not be taken at face value,
yet.

~~~
hexl
> but without a randomized control trial, there is no way the success can
> reliably be attributed to the medications

That's non-sense, if everyone that had cancer got cured by a miracle drug,
would you still demand a randomized control trial?

~~~
gus_massa
Yes! I want to be sure that this miracle drug is 100% to eliminate all the
other drugs that has nasty side effects and have a lower effectivity.

Let's pick some terminal ill patients. I think cancer metastasis in the brain
has a very bad prognosis, like less than a year of life expectancy [1]. Let's
make a one year trial: 100 patients in the control group that receive the
usual treatment and a placebo. 100 patients in the treatment group that
receive the miracle drug instead of the placebo. Obviously a double blind
study.

If the terminal patients selection was good enough, after a year you will get
90 death in the control group (there are some lucky guys) and only 5 death in
the treatment group (someone died in a car accident). That would be very
convincing and in a few years (with a few additional studies) it will remove
all the current drugs from the market.

Without a serious study, some doctors will believe in the miracle drug and
some will have the gut feeling that another drug or drug combination is better
and continue using the old treatment. The lack of a convincing study kill
people.

And also, there is the risk of snake oil. Some doctors are convinced that a
drug cures 100% of the patients and push it to be applied to everyone.
Sometimes they are wrong, without a study it is impossible to separate the
good and the bad ideas. The lack of a convincing study kill people.

[1] Unless it a metastasis of breast cancer and is affected by hormones? I
think there a few exceptions, but it is usually very bad.

~~~
Dylan16807
So you have a cancer that normally has a 90% fatality rate after a year.
Someone gives you evidence that they gave this drug to everyone with this
cancer in their hospital, and 70/73 survived for a year. Not properly
randomized, not properly controlled. Would you really reject their data and
find it unconvincing?

~~~
gus_massa
If the results are so good it would be impressive. But it will be necessary to
take a look at the data. Dollar to doughnuts they have a horrible
methodological mistake, like a bad classification of the patients, or using a
weird definition of cure [1], or cherrypicking the patients that get cured.

[1] We have a big announcement of a miracle cure in Argentina in 1986. It was
crotoxina [links bellow] that is a part of the venom of some snakes. One of
the problems was that they were comparing CT from different angles and finding
fake reductions in the size of the tumors. (Other parts of the study were just
frauds.)

[https://translate.google.com/translate?sl=auto&tl=en&u=https...](https://translate.google.com/translate?sl=auto&tl=en&u=https%3A%2F%2Fes.wikipedia.org%2Fwiki%2FCrotoxina)

[https://translate.google.com/translate?hl=&sl=es&tl=en&u=htt...](https://translate.google.com/translate?hl=&sl=es&tl=en&u=https%3A%2F%2Fwww.clarin.com%2Fediciones-
anteriores%2Fcrotoxina-ilusion-duro-demasiado_0_S1xMQNxJUhe.html)

[https://translate.google.com/translate?hl=&sl=es&tl=en&u=htt...](https://translate.google.com/translate?hl=&sl=es&tl=en&u=https%3A%2F%2Fpulperiaquilapan.com%2Fcrotoxina-
un-invento-argentino-que-cura-el-cancer%2F)

~~~
Dylan16807
Valid issues, but you can have all of those problems in a randomized
controlled trial too. That's not a very compelling argument that the non-
random poorly-controlled version is any _worse_ in this hypothetical.

~~~
gus_massa
For example if the "usual" death rate is 90% and you select some group of
patients for security reasons, like 18<=age<=60, perhaps the death rate is
reduced to 80%. If the testing and control group is randomized, then if there
is no effect of the drug you will get the same 80% in both groups. If the
group is not randomized, you can't be sure that any of the selection criteria
is the cause of the improvement.

~~~
Dylan16807
You can look at the selection criteria and perform an analysis. If the data is
clear enough, you can still pull a signal out of the noise. I assume that's
the reason you took a 70/73 survival rate in the hypothetical I posed and
reduced it to 20% in your version. And to be clear, in my version it's a
general hospital and they give the treatment to everyone that has this
diagnosis. There are no intentional selection criteria, it's mostly just who
lives in the area.

~~~
gus_massa
[Sorry for the late reply.]

> _If the data is clear enough, you can still pull a signal out of the noise._

It is theoretically possible, but very difficult. Unless you use a lot of
people in the trial, but then you must ensure that the measurements are done
in a consistent way.

> _in my version it 's a general hospital and they give the treatment to
> everyone that has this diagnosis_

Does it include pregnant women and babies with less than 1 year? Does it
include people with more than 90 years? Does it include people that goes to
the hospital in an ambulance because they are almost dying, like a hearth
attack? Does it include someone that had one of the lungs removed and is under
a chemotherapy treatment?

What about people that can't sign the form for the experimental treatment?
Just signing a form is a selection of people that is not toooooooooooooooooooo
bad.

What about asymptomatic people? Does your are has the same policy to test
everyone/someone/noone than the region you are comparing with? What about the
effects of temperature or humidity?

What about diet? Poor people may have a bad diet, with a low amount of
vitamins and that can affect the illness. Some countries drink a lot of milk
and some very few, some countries add vitamins to the milk.

What about the median income? If the city has a few hospitals, there will be
one closer to the poor area and other closer to the rich one. Some people has
health plan that include one hospital(s) but not other hospital(s). How does
it affect the selection of people in the hospital? Different countries have a
different definition of poor.

Some hospital are famous and get more of the strange/difficult cases after the
standard hospitals give up or realize it is a complex case.

I may be missing other factor, or overestimating some of them, but it is very
difficult to be sure that you know all the things that change the cure rate
and that you can correct the result.

------
mrfusion
I think this drug has become too politicized to be able to have a factual
scientific debate.

~~~
jacquesm
"If there was any effect of this drug on COVID-19, it was minimal.
Hydroxychloroquine, whose toxicity is far lower, may be safer than
chloroquine. But that doesn't matter if the drugs are ineffective."

What's political about that?

The whole idea that if there were a simple and cheap cure that it would be
politicized to the point where it won't see widespread application is
ridiculous.

~~~
shripadk
> What's political about that?

Then why does the title say that Hydroxychloroquine "probably" isn't the
answer? It either works or it doesn't. If the drugs are ineffective just say
so. Why beat around the bush with a "probably"?

~~~
jacquesm
Probably as in 'not yet 100% sure'. As a measure of probability based on
available evidence.

~~~
Natsu
To me, the headline reads like it's saying "this probably won't work" rather
than "we don't yet have enough evidence to say that this works." If I had to
headline this article, I probably would have written something like
"Hydroxychloroquine data still inconclusive, don't get your hopes up yet" to
better convey the meaning.

From reading it, what the article actually supports is that we have seen two
trials that are inconclusive. This is the meat of it in my view -

==

A French study of HCQ suggested that it had was effective in decreasing the
viral load from nasal secretions. When azithromycin was added the magnitude of
the effect was larger.

[...]

And a Chinese study of 30 patients doesn't prove that HCQ worked. Or that it
doesn't. But the two groups, control and treated, showed no difference in the
amount of virus in the throat on day seven, the length of time for the fever
to go away. There was an apparent difference in the progression of the
infection (determined by x-ray), in the two groups but this means little since
5/15 treated patients got worse vs. 7/15 in the control group. This effect
could easily be by chance and nothing to do to the drug. Furthermore, this
trial did not include azithromycin, so it cannot be compared to the French
trial.

------
nradov
Why is this flagged? It seems like an interesting article from a reputable
source.

~~~
downerending
I'm guessing it's because the organization has been praised by a number of
well-known people on the right (e.g., Steve Forbes, Ben Carson).

And because the question of whether or not this drug works, or even should be
used at all, seems to have become highly politicized. I think I read that at
least one US governor threatened to pull the medical license of any doctor
that used it.

I don't have any idea whether this drug might be useful, but I think our most
boring, apolitical scientists should be making that call. It could well end up
that it sort of works, some of the time, perhaps in combination with other
drugs or factors. Conceivably this will be solved the way AIDS ultimately was,
slowly zeroing in on a set of treatments that mostly work.

~~~
nradov
US state governors don't have the authority to pull medical licenses.

~~~
downerending
Perhaps. I believe that doctors are licensed at the state level, and if I were
a doctor, I wouldn't care to cross a governor making such a statement.

