
Chloroquine, past and present - ilamont
https://blogs.sciencemag.org/pipeline/archives/2020/03/20/chloroquine-past-and-present
======
duchenne
Since this 13th of February, the Koreans recommend the use of hydrochloroquine
for patients infected by the covid-19 [1]. The Covid-19 fatality ratio in
Korea is one of the lowest in the world, around 1%.

The study in France showing a spectacular drop in covid-19 viral load after
only 6 days of hydrochloroquine treatment has been directed by Pr Didier
Raoult who is the most cited researcher on infectious disease in the world.
[2]

Anecdotally, I personally know a patient who took hydrochloroquine, and indeed
the viral load dropped quickly, even though the lung damage is still there.

According to Pr Didier Raoult, the hydrochloroquine has been routinely
prescribed for decades to prevent Malaria, with well known and limited side-
effects.

According to him, the in-vitro effectiveness of hydrochloroquine on covid-19
has been confirmed by several labs independently, including his own lab and
the lab of Mr Zong the most cited researcher on infectious disease in China.
(Sorry, I am not sure about the spelling)

[1]
[http://m.koreabiomed.com/news/articleView.html?idxno=7428](http://m.koreabiomed.com/news/articleView.html?idxno=7428)
[2]
[https://scholar.google.fr/citations?user=n8EF_6kAAAAJ&hl=fr](https://scholar.google.fr/citations?user=n8EF_6kAAAAJ&hl=fr)

~~~
roenxi
I'm reminded of the old armour-where-the-bullets-aren't story [0]. The most
important things to watch out for are places where symptoms don't show up at
all.

One interesting challenge that the people doing studies must be facing is that
by the time symptoms get bad the virus is probably to some degree irrelevant.
If someone's lungs have given out then whether or not there are virus
particles in their body probably doesn't matter so much; the damage is done.
Raw viral load isn't putting people in hospital as much as that important
parts of their body have been dissolved.

For a drug to be effective against the virus maybe it needs to be cheap &
administered very early before symptoms become too obvious. That'd be hard to
study.

[0] [https://medium.com/@penguinpress/an-excerpt-from-how-not-
to-...](https://medium.com/@penguinpress/an-excerpt-from-how-not-to-be-wrong-
by-jordan-ellenberg-664e708cfc3d)

~~~
kayamon
There's actually a team at the University of Minnesota doing that study right
now.

[https://www.reddit.com/r/medicine/comments/fkb0wa/university...](https://www.reddit.com/r/medicine/comments/fkb0wa/university_of_minnesota_covid10/)

------
cameldrv
We definitely want more studies, but IMO we're reaching a tipping point. We
have anecdotal evidence from China and South Korea, and this quite flawed, but
at least data-containing study from France.

Chloroquine's safety profile isn't great, but the safety profile of COVID is
way worse. If you look at Chemotherapy for example, one would never take any
of those drugs unless you had cancer.

COVID isn't quite as bad as cancer, but Chloroquine, especially for a short
course, isn't anywhere near as bad as most chemo drugs. Many people take it
for years as prophylaxis -- not even to treat an existing disease.

~~~
gumby
> Chloroquine's safety profile isn't great, but the safety profile of COVID is
> way worse. If you look at Chemotherapy for example, one would never take any
> of those drugs unless you had cancer.

The FDA's Office of new drugs is split into divisions (dermatology, oncology
etc) and the different divisions have different approval criteria as you
mention. From my Onco friends' PoV, cancer patients are pretty much assumed to
be dying anyway so the standard of risk is quite different from, say, Derm,
whose patients don't really die of anything except cancers.

Note: I have presented to the FDA and have written clinical trial requests
(e.g. IND) which have been approved, but I have never done a submission to
OOD. However my friends who do really talk about the approval path in a
different way than I used to.

Don't self-medicate with chloroquine. It's very hepatotoxic.

~~~
cameldrv
I appreciate an expert opinion here. What do you think is the actual rate of
adverse events from Chloloroquine, and of what severity?

~~~
jennyyang
One of the comments in the article:

I prescribe Plaquenil extensively in patients with autoimmune conditions.The
safety profile of this drug is excellent. It is also still used for malaria
prophylaxis in healthy individuals .it is not a new drug. I don’t see the
reason of labeling it as dangerous. The question is : does it work for Covid19
prevention and treatment? The answer is “the current limited evidence suggests
that it does”. What i can tell you that I am aware of a number of doctors in
the US who are currently infected or waiting for results who are taking the
drug. And I cannot blame them.

~~~
paulmd
This whole incident hasn't done much to shake my impression that US doctors
are interested first and foremost in making sure they get their "cut" on every
prescription, even when the drug is relatively innocuous.

Like fine, we can have this discussion about chloroquine. It's behind-the-
counter in the UK, so on par with sudafed in terms of access control, and OTC
in a lot of countries that actually have to deal with malaria directly. But
the same argument gets applied to stuff like oral contraceptives, which are
straight-up OTC in a lot of countries too, and can simply be discontinued if
you notice symptoms.

At the same time, we allow drugs with insanely narrow theraputic ranges like
tylenol/acetaminophen/paracetamol (seriously, almost as bad as the chloroquine
people are freaking out about, a normal dose is 1-4g and a lethal dose can be
as low as 5g) to be sold OTC here with no questions whatsoever. We allow
combination products despite obvious risks for multiple dosing, we allow
combination products to "dissuade addicts" from abusing opiods (like any
addict has ever been dissuaded by a risk bodily harm). And doctors don't make
a peep about that, because they're not accustomed to getting their cut on that
one.

That's also why the AMA resists nurse practitioners so hard. The truth is, a
lot of those drugs really should be "behind the counter", a pharmacist should
simply have to give you a quick rundown of possible symptoms and what to do if
you notice them (discontinue and see a doctor or go to a hospital depending on
urgency, same as you would do with a doctor-prescribed drug), but doctors
won't allow that because they wouldn't get their cut, so we just call them
"nurse practitioners" instead.

US doctors really like playing gatekeeper, to a much greater extent than other
countries (where coincidentally, money doesn't come into the picture as much).

~~~
pkaye
Do doctors "get a cut" when their patients buy from a neighborhood pharmacy?

~~~
paulmd
They get a couple hundred bucks for a 5 minute office visit to write the
prescription, yeah.

I'm fine if there's a serious reason for a physical examination, but a lot of
stuff the doctor is effectively filling the role of a pharmacist: telling you
side effects and if you have this set of serious side effects then to stop it
and/or go to a hospital, here's your script, pay at the front desk. A lot of
stuff is unnecessarily shoehorned into Rx-only, and despite a lot of talk
about "reducing costs" there is no real drive to actually do so.

A great example is oral contraceptives. You may have to try a couple different
blends before you find the right mix for your body. Some of them will be
uncomfortable. Some may cause dangerous bleeding and you need to go to a
hospital. There is not _zero_ risk here, or with any drug. But the doctor has
no way of telling which might be which for your particular body, they are
there to tell you the risks, sign the paper and let you try it out. And that's
why oral contraceptives specifically are being looked at as something that
could be moved out of Rx only and to either OTC or pharmacist-prescribable -
but the problem is there are really a lot of drugs that don't belong there.

A pharmacist can read the risks to you just as easily and not charge you $250
for a 15 minute office visit and another $250 for a one-month followup 15
minute office visit.

I have lots of 6-month maintenance visits that are literally 5 minutes.
Everything going well? "Yup!" "OK, we'll call in your prescription, pay up
front". They're just using their gatekeeping power to extract a check.

~~~
jac241
They don't make a couple hundred bucks. A 99213 established outpatient visit
is worth 0.96 work RVUs * $36.0391 Medicare conversion factor = $34.59 for a
standard outpatient visit. Even if you add the facility RVU = 0.48 +
malpractice RVU 0.08 that is $54.78 for an outpatient visit. To make a couple
hundred bucks, you need to do something like placing a stent for someone who
is having a heart attack: CPT code 92941 - 12.31 work RVUs = $443.64.

All this information is available online. You can look up the physician fee
schedule straight from the CMS. [https://www.cms.gov/apps/physician-fee-
schedule/search/searc...](https://www.cms.gov/apps/physician-fee-
schedule/search/search-results.aspx?Y=0&T=2&HT=0&H1=92941&M=5) . Here are the
cardiology codes - [https://myheart.net/cardiology-coding-center/coronary-
interv...](https://myheart.net/cardiology-coding-center/coronary-intervention-
cpt-codes-and-rvu/)

To add an additional data point, doing a heart transplant is 89.50 wRVU *
36.0391 = $3225. I don't think doctors are living as well as you think. CPT
code 33945.

~~~
paulmd
Providers don't bill Medicare rates to normal patients, so none of that is
valid.

Providers in fact make a point that they lose a significant amount of money at
Medicare rates and have to limit the number of Medicare/Medicaid patients they
see as a result.

I can confirm that a "45 minute" (5 minutes with nurse taking vitals, 25
minutes waiting in office exam room, 15 minutes with doctor) specialist "new"
office visit was just billed to me for $246. They didn't charge me half the
rate they charge a heart attack, they charge the heart attack patient 100x as
much.

I don't think you understand how US billing works. Probably not from the US,
or probably not subject to the system due to age (child or senior) or
privilege (an engineer on a cadillac PPO plan perhaps).

Anyone who has ever experienced the US system knows that's absolutely normal.

~~~
jac241
You said physicians get paid a couple hundred bucks for each visit. I provided
the source that says how much a physician gets paid by medicare for an
established outpatient visit. An outpatient visit for a new patient (99203) is
1.42 wRVU + 1.48 facility RVU + 0.13 malpractice RVU = 2.14 RVUs = $109 for
Medicare. A complex new visit (99205) is 3.17 wRVU + 2.40 facility RVU + 0.28
malpractice RVU = 5.85*36.06 = 210 dollars. The facility RVU is the amount
given to pay for staff, rent, and other overhead. In general, if a physician
is employed, they are getting just the wRVU for the visit.

For outpatient visits, this source says medicare pays 92% of what private
insurance pays for established outpatient visits, and 80% overall
[https://money.cnn.com/2014/04/21/news/economy/medicare-
docto...](https://money.cnn.com/2014/04/21/news/economy/medicare-doctors/) .

I am a US citizen who used to be a software engineer who now attends a US MD
Medical school and I have student health insurance.

For the heart attack patient, it isn't the physician who is charging the huge
amount. It's the hospital. The physician is only going to get a certain factor
(somewhere between 1x - maybe 3x on the extreme end) of that $440 for the
wRVUs.

~~~
paulmd
And like I said, billing for normal patients isn't determined on
medicare/medicaid rates and those are widely noted to be far lower than break-
even let alone private billing rates.

> The researchers found the gap between the prices Medicare and private
> insurers pay hospitals increased from 2015 to 2017. Specifically, the
> researchers found private insurers in 2015 on average paid 236% of Medicare
> rates, and by 2017 that grew to 241% of Medicare rates.

[https://www.advisory.com/daily-
briefing/2019/05/13/hospital-...](https://www.advisory.com/daily-
briefing/2019/05/13/hospital-prices-rand)

Again, I just provided you an example of me getting billed $250 for 15 minutes
of physician time during an office literally this month. Right now. Just paid
it today. Will seeing the bill solve this discussion for you?

> For the heart attack patient, it isn't the physician who is charging the
> huge amount. It's the hospital. The physician is only going to get a certain
> factor (somewhere between 1x - maybe 3x on the extreme end) of that $440 for
> the wRVUs.

That's not what we were discussing, you're changing the topic from an office
visit to a heart attack. A doctor's office visit is mostly doctor time,
there's no surgical ampitheatre necessary for an office visit. No recovery
time in a hospital bed. Completely different situation.

$1000 an hour net billing rate for a specialist office visit sounds about
right. That's what I just got billed.

And yes, student insurance is unusually generous and usually subsidized by the
university in terms of provider reimbursement as well as direct rates. You are
not paying the full freight there.

Furthermore, you are far, far off the reservation suggesting the normal
billing for a heart attack is $3200. You are underneath the Dunning-Kruger
curve here, you don't even know what you don't know and you think you are
informed for it.

> Heart attack hospitalizations cost a median $53,384 and strokes cost
> $31,218, according to the study. The resulting catastrophic costs make it
> difficult for uninsured patients to keep up with basic living expenses such
> as transportation and housing, according to researchers.

[https://newsarchive.heart.org/uninsured-patients-faced-
devas...](https://newsarchive.heart.org/uninsured-patients-faced-devastating-
hospital-bills-heart-attack-stroke/)

Feel free to tell the American Heart Association that they're wrong by a
factor of 15. Let me know when they update the article. You're wrong, it's no
longer worth continuing the debate with you.

Again, like I said, I mean this in the gentlest possible way: if you think an
average heart attack billing (not just for the doctor, the whole thing) is
$3200, you're too privileged to have been exposed to the realities of the
American system. You are more incorrect than you have the worldview to even
grasp. Even the doctors' association themselves think you are wrong.

~~~
jac241
I get that a heart attack hospitalization is expensive, $55k on average. The
physician is not pocketing all of that $55k. They aren't the ones charging
that, that is the hospital. The physician will get ~$1k of that (look below
for the calculation). Please try to be charitable in your evaluation of my
ability to reason here.

I'm not trying to change the topic from office visit to heart attack. I
provided the RVU calculation for the outpatient visits. That is how much the
physicians are getting paid. You said that physicians are making a couple
hundred bucks of each outpatient visit, which I don't believe is accurate, and
I provided the calculation of why I don't think that is accurate. The total
cost of the visit can be $250, but the physician is not getting anywhere near
that.

I don't think it's accurate to say that they will be able clear $1000/hr.
There is additional time needed to document each patient (often equal to the
amount of time seeing the patient). I think seeing 3 visits in that time is
plausible, but the physician is not getting that whole $250 (which is the
point I'm trying to make). The clinic revenue may be $750 for that hour, but
that needs to cover all of the overhead, and the physician will get whatever
is left.

Make sure you are looking for sources that compare how much the private
insurance pays physicians compared to medicare in particular vs how much they
pay hospitals compared to medicare. The numbers will be different.

The $53,384 is what the hospital charges for the heart attack. The physician
only gets the wRVUs for the services they provide in the hospital (if they're
employed), so the 12.56 wRVU for the cardiac revascularization + the admission
history and physical (2.61 wRVU CPT 99222) however many days of progress notes
(2.00 wRV 1x each day - CPT 99233) in the hospital and the discharge summary
(1.28 wRVU - CPT 99238) they write for the patient. So if a patient got
revascularized and were in the hospital for 4 days before being discharged
that's 12.56 + 2.61 (admission day) + 2 * 2.00 (2 inpatient days) + 1.28
(discharge day) = 20.45 wRVUs for the admission = $737 for the physician for
that hospitalization.

I'm trying to make the distinction here between how much the hospital gets
paid vs. the physician who provided the care. It's not accurate to say the
physician is making $53,384 for the heart attack hospitalization, that is what
the hospital is charging. The physician may make ~$1000 for an admission like
that. If the physician is self-employed or in a group, they will charge for
the facility RVUs and malpractice RVUs as well, because they need to cover the
overhead of having a clinic to see the patient after the hospitalization.

If your bill breaks down the overhead for the clinic separate from the
physician charge, then I'll agree that the physician made the $250 straight
cash, but I don't think that is in any way the average amount any kind of
doctor will make off an outpatient visit. Look at what you're suggesting, that
a physician makes $1000/hr * 2080 workable hours in a year (not likely a
physician only works 40hrs a week..) = $2+ million a year.

------
axguscbklp
It seems to me that we should immediately move to massively increase
production of hydroxychloroquine. If it turns out to be part of a solution,
great. If not, I doubt that more than a tiny fraction of the total resources
dedicated to the pandemic would have been used up by the effort. There is no
time to take things slowly in our situation. In any case, from what I've read
on places like r/medicine, many people who have access to hydroxychloroquine
have already begun to hoard it. So one way or another, if we do not ramp up
production there will be trouble.

Hydroxychloroquine has been around for decades, so it's not like we would be
jumping into a total mystery about its side effects.

It seems to me that, whether hydroxychloroquine ultimately turns out to be
effective or not, it is the closest thing we have right now to something that
might prove to be a very helpful medicine.

~~~
pbreit
Supply is not an issue: [https://www.fiercepharma.com/pharma/new-commitments-
mylan-an...](https://www.fiercepharma.com/pharma/new-commitments-mylan-and-
teva-move-to-supply-tens-millions-hydroxychloroquine-tablets-to)

We need testing that the medical community will accept.

~~~
qes
> Supply is not an issue

Well, I was going to order some, been researching for a couple days before
buying, and in that time all stock on my known pharmacy sites is now gone.

~~~
hn1970
How does one find these sites? I've never been able to determine which are
reputable

~~~
qes
I literally just googled it. Read around for people's experiences ordering.
Picked one to try. Same way you'd find info about anything you're looking to
buy on the internet. They delivered and the meds were clearly effective, been
using the same place for a decade now. I've also tried a couple others over
the years when looking for something my main site didn't carry. Never been
burned.

------
pazimzadeh
Also take a look at thymoquinone, which supposedly inhibits mouse coronavirus,
which is very similar to SARS-coronavirus.

The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis
(Cs) extracts on the replication of coronavirus and the expression of TRP
genes family
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933739/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933739/)

Thymoquinone is also generally protective of lung health in several models:
[https://www.tandfonline.com/doi/abs/10.1080/10520295.2019.16...](https://www.tandfonline.com/doi/abs/10.1080/10520295.2019.1681511)
[https://www.ncbi.nlm.nih.gov/pubmed/31044379](https://www.ncbi.nlm.nih.gov/pubmed/31044379)
[https://www.ncbi.nlm.nih.gov/pubmed/31143688](https://www.ncbi.nlm.nih.gov/pubmed/31143688)

It is found in orange peel and black seed (Nigella sativa) extract.

~~~
taneq
Pardon the dumb question, but has anyone just tried quinine? I've been
wondering if a hefty gin and tonic would help matters.

~~~
red-indian
I'm taking it, I've also got my family and neighbors on it. I was unable to
convince doctors since February to take me seriously that hydroxychloroquine
is likely to have prophylactic effects so I took matters into my own hands. I
know what I'm doing. Those who don't know what they are doing should not just
jump in since they need to manage and understand the dose, the drug
interactions, and the side effects. None of which are a problem for most
people. Most. The ones that aren't though the interactions are well enough
known and documented. I am not recommending it to anyone, that would probably
be a crime. I'm saying if you're smart and understand science and thoughtful
and not reckless you might be able to use it with the same safety that indians
did for thousands of years. I still don't think you should though. Push for
HCQ instead.

Commercial tonic is limited by federal law to 20mg per 8 oz, so I make my own
tonic.

It would be much much better and would likely stop this whole problem if we'd
just mail prophylactic doses of HCQ to the whole population instead of mailing
a $1500 check to everyone like they've decided instead.

It's very humorous how people look at tropical countries that still have
widespread HCQ use for anti-malaria and announce that they must be
undercounting cases since their reported numbers are far too low. No, their
numbers are not too low. It's just a lot of people in these regions are
essentially vaccinated.

~~~
entee
I think you’re missing one of the key parts of the article: be careful. Mass
administration of a drug is dangerous. As you mention early in your post, you
know what you’re doing, I take you at your word. But a drug with known serious
side effects shouldn’t be mass distributed without clear benefit. Studies so
far are encouraging but tiny and noisy sample size. We’ll get better data
soon.

Even then, if it proves effective in symptomatic cases, it’s unclear
prophylactic use is called for. More sensible to administer to those with
current symptoms. If truly effective this would lower fatalities and keep ICUs
from being overwhelmed.

Finally, the most recent French study suggests a combination with azithromycin
is the actual effective treatment. We just don’t know enough yet, we will
soon, let’s be responsible.

------
fny
I was under the impression that chloroquine was used to facilitate cellular
absorption of zinc and that the zinc was responsible for any antiviral
behavior:
[https://www.youtube.com/watch?v=dT6mHi_8V5E](https://www.youtube.com/watch?v=dT6mHi_8V5E)

~~~
tristor
I was under the same impression. Zinc acts to disrupt cellular replication of
viral cells, and this is true for MANY viruses. Cloroquine acts as a zinc
ionophore providing a pathway for zinc to cross the cellular wall at much
lower concentrations, greatly improving its effectiveness.

------
transreal
This is pretty interesting. I've been taking Plaquenil (hydroxochloroquine)
regularly for 6 months now to control an auto-immune disease, and I came down
with potential symptoms of covid-19 2 weeks ago, but it was very mild - just a
sore throat and cough that lasted 4 days, and I had a slight fever the first
night. I self quarantined just in case, but after recovering thought I must
have just caught a cold, since my symptoms were so mild. But I wonder now if I
got it and if taking Plaquenil helped me recover quickly.

Too bad I can't get tested to know for sure :-(

When I started Plaquenil, the doctor told me it takes about a month or two to
really build up in the blood stream to help control my condition. I wonder if
the need to take it for a while also applies for Covid-19.

~~~
axaxs
Please remember that greater than 90 percent of people who have covid like
symptoms test negative. So while there's a chance you had it and recovered,
it's very small. Stay safe and assume you're still vulnerable.

~~~
jennyyang
90% of _tests_ reported negative. If someone is tested, they need to take 2
tests. If someone is tested positive, they need to be tested until they get 2
negative tests in a row. So the numbers are very skewed.

~~~
axaxs
This is good info. Are you suggesting that most people would get 3 tests...a
confirmation, then after x weeks 2 negatives, skewing the number potentially
up to max ~66% testing negative even for people with the virus?

------
guiriduro
Is there not an argument that given chloroquine's apparent efficacy, albeit
statistically weakly or improperly demonstrated (so far), along with its long
history of relative safety in anti-malarial prophylaxis (with known caveats),
set against an exponential growth in dangerous pneumonia - it is therefore
rational to want to at least offer it to all suspected cases and healthworkers
in balance of the serious risks they face?

~~~
hannob
The possible side effects include permanent blindness.

Giving this drug to people while you simply don't know if it does any good is
only justifiable if you do it within a properly designed clinical trial. Which
is the thing you should do. If you feel lots of people should get this drug -
do a large trial. Will give us better data.

~~~
nshepperd
If you take it for years. Why is everyone ignoring that part?

~~~
1996
because it doesn't generate enough offense. most online arguments seems to be
attempts at creating the maximum possible offense to create "engagement"

the fact you need to have 1 kilogram of chloroquine during years of treatment
is an inconvenient complicated fact, while the emotional appeal of blindness
scores more indignation.

------
ggm
I think the drug combinations are going to turn out to be as important as the
single instances. One to bind to receptors. One to limit related infection
risk. One to be an anti-pyretic.

This is how HIV was fought, with cocktails. Single drug treatment comes later.

Chloroquine is a powerful drug. It needs to be treated with respect. Yes it is
cheap. it also has effects on the mind and we don't need a wave a psychosis to
follow the corona-virus illnesses.

~~~
Red_Leaves_Flyy
We've already weathered at least one wave of panic induced psychosis. From
panic buyers, to Congress members using privileged information to blatantly
sell stock just before the first crash.

~~~
save_ferris
Neither of those are examples of psychosis. Overreactions to unusual
instability in our society? Sure, but hyperbolic comparisons like this muddy
the waters around what psychosis is.

------
andreygrehov
Does anyone have any information about the Favipiravir testing going on in
China? From what I read, it has a 90% success rate treating coronavirus AND is
a super safe drug in general.

~~~
gnulinux
I read this X% success rate for many drugs, Remdesivir, chloroquine etc...
What does it mean? Giving no drug, just ventilator alone has 97% success rate
right? So how do we know that that 90% is due to the drug and not, you know,
immune system itself? Moreover, a lot of people keep saying both Remdesivir
and chloroquine are in official treatment suggestions in Italy, and seeing
Italy is suffering a pretty bad mortality rate, how do we even know these
drugs are better than placebo?

~~~
mypalmike
Was 97% a hypothetical? I have heard much lower figures for ventilator success
rates.

~~~
gnulinux
Do they use these drugs only to severe patients who need ventilator? I was
referring to the overall estimated CFR (3%). What is the success rate of
ventilators then?

------
brucer
I was intrigued by the results from the recent quick french study:
[https://www.mediterranee-infection.com/wp-
content/uploads/20...](https://www.mediterranee-infection.com/wp-
content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA.pdf)

I read through the paper, and it's not immediately obvious, but if you look at
the two graphs at the bottom, the hydroxychloroquine is 75% effective in the
first chart, but only 50% in the second one. That's because the actual test
was:

Control: 16

hydroxychloroquine: 14

hydroxychloroquine + azithromycin: 6

The first chart includes all 20 people who got hydroxychloroquine - including
the 6 who also got azithromycin.

My question: do we know how effective azithromycin would be on it's own? Maybe
it's the wonder drug we should be focused on, which would be great since it's
available everywhere.

It should go without saying these are VERY preliminary results from a small
trial but it's something!

~~~
Nav_Panel
It's an antibiotic. Severe patients will be dealing with secondary (bacterial)
infections, so it makes sense to use both. But on its own, I expect it would
have little effect.

~~~
alkonaut
It’s already commonly used as both treatment and profylactic (in healthy risk
group patients) for viral pneumonia. _Why_ it works for I think is still not
entirely clear.

Being an antibiotic is also convenient because many times you would also get
antibiotics to prevent a secondary infection from bacteria.

It’s not exactly a miracle cure (like an antibiotic is against a bacterial
pneumonia), but doctors have few tools when it comes to viral pneumonia, so
even something that helps a little is welcome.

------
ropiwqefjnpoa
Quinine is amazing stuff and quite easy to make, but the poison is in the
dosage. Controlling that when you're making your own with cinchona bark isn't
something you want to do trial and error style, serious side effects.

------
jojo2000
There are papers out there that qualify chloroquine and derivates as effective
in case of viral infections with viruses related to covid-19 [0] and try to
explain what the mechanism could be :

« The exact mechanism of antiviral intervention by chloroquine is not yet
elucidated but is possibly a multitarget mechanism, depending on the time
point at which the drug is added »

[0]
[https://aac.asm.org/content/53/8/3416](https://aac.asm.org/content/53/8/3416)

------
Mountain_Skies
How well does chloroquine mix with gin? Asking for a friend.

~~~
munk-a
It's much more often to mix in Quinine - and you're doing so every time you
have a gin & tonic (with real tonic - not just carbonated water). Amusingly
it's also an anti-malarial.

------
macinjosh
I realize that the FDA serves a purpose, but in dire situations I think anyone
should be able to take any drug if they sign a document stating they will hold
no one liable for adverse affects of a drug that might have chance of saving
their lives. Why does one have to follow the state's one-size-fits-all rules
when their life is at stake and any potential harm is limited to themselves?

~~~
odyssey7
It’s an interesting question what aspects of human behavior the government
should be able to regulate.

A couple of points beside that are 1) this would incentivize drug companies to
use desperate patients as a low-cost way of screening drug candidates — “free”
data with all liability signed away. And 2) the externalities of a person
being injured can be huge, so the possible harm isn’t really limited to that
patient.

Edit: With some reasonable guardrails, I think “right to try” makes sense. I
personally don’t know what the guardrails should be.

------
cgio
Given the relationship with Malaria, does anyone know if correlation with G6PD
has been subject of research? G6PD is a common genetic Deficiency that
provides immunity from malaria. G6PD people have to avoid consuming e.g. blue
colour, sulphites and other anti malarial drugs, aspirin, fava beans etc. at
risk of haemolysis.

------
fspeech
As non-specific antivirals the benefits of these drugs are most likely at
disease onset or as preventives. A trial has started in the US for people with
known exposure:
[https://clinicaltrials.gov/ct2/show/NCT04308668?term=hydroxy...](https://clinicaltrials.gov/ct2/show/NCT04308668?term=hydroxychloroquine&recrs=ab&cond=COVID-19&draw=2&rank=4)

Note the dosage being trialed is quite high. Definitely not something to do
without proper medical supervision.

------
known
[https://en.wikipedia.org/wiki/Chloroquine#COVID-19](https://en.wikipedia.org/wiki/Chloroquine#COVID-19)
is not suitable for people with heart disease or diabetes

------
AdmiralBumbleB
This chloroquinine rush is already out of control. My pharmacy is already out
of it and is unable to procure from other pharmacies (which are also out
already!)

My pharmacist placed orders for all her patients to prefill prescriptions
(where possible) for the next few months.

I can understand a shortage when there's a clear evidence-based need, but the
rumour-mill hasn't even ramped to full bore yet and it's already harming
people with a pre-existing need for the medication.

It's even worse _if_ the medication works to prevent or shorten c19
infections, because the people currently taking chloroquinine are very likely
high-risk (immunocompromised) patients.

Really wish people would chill out.

Note - This affects me, as I take the medication. It's scary to think I could
be without it at some point in the future as it's been practically life-
changing.

~~~
altcognito
This is where having a fully funded CDC and pandemic team in the US pays off.
They would have been paying very close attention for weeks on end in China,
Italy and South Korea and many approaches could have been already dead-ended
before it even significantly reached out shores.

To say nothing of actually being in the process of ramping up medications that
_HAVE_ shown to be effective. It feels like we are starting from ground zero
when that should simply not be the case.

~~~
throwaway894345
I think everyone would like to see the CDC be better funded. Hindsight makes
that an obvious mistake, but monitoring C19 should have been their number one
priority in any case. From January onwards it was clear that it was the number
one threat. There's still no explanation (afaik) for why they rolled their own
test instead of using the WHO's test, nor have they effectively communicated
their plans for ramping up testing or medical capacity. I don't see how this
is anything besides mismanagement (e.g., how does funding impact which test
they used? Presumably being under-funded would prompt them to use the test
that the rest of the world is going with instead of rolling their own), and I
really hope congress or the justice dept rips into this after the crisis is
averted.

EDIT: Note that I say all of this as someone who is a big believer in "it's
almost always more complicated/nuanced than it looks", but there seems to be
no information about said nuance or complexity.

~~~
makomk
There seems to be a really obvious explanation of why they rolled their own
test instead of using the WHO's test: there was no WHO test when they did it,
the two different tests were developed in parallel (and they're not the only
country which developed their own test either, there are something like seven
different ones used in various countries). The CDC had already been using its
own test internally when the WHO announced the alternative German one they'd
been using. Then when the CDC test didn't work when rolled out to labs, it's
not like the WHO could have supplied them with testing kits instead. The CDC
would have had to produced the WHO-designed test itself, verified it worked,
arrange for it to be mass produced, and hope that the same problem didn't
happen - all whilst their test rollout was massively delayed by essentially
starting from scratch. Most of the media just doesn't seem to be interested in
explaining this.

~~~
throwaway894345
I didn't see any such explanation on the CDC page either, and I thought I was
pretty thorough in searching for it. I did know that they were developed
concurrently, but I'm unaware of any information about why they couldn't at
any point pivot and use the WHO test, for example. Why is this information so
hard to find?

------
Animats
Yesterday's paper from the COVID-19 hospital in China mentioned chloroquine.
They use it, but only in a few specific situations.

------
sabujp
hydroxychloroquinine should be readily available in pharmacies in India. I
expect many to start using those when they're in bad shape.

------
hprotagonist
_And so to today. As I said yesterday, I find the reports of chloroquine
/hydroxychloroquine activity against the coronovirus very interesting, but
preliminary. There has as yet been no well-controlled trial, and unfortunately
the effects seen are still the sort of thing that can look exciting but
disappear when you look closely. I mean that. It happens all the time – ask
anyone else who does drug research for a living. If this drug isn’t useful,
then sending hundreds of millions of people out to swallow all of it that they
can find will be a massive waste of time and money, and will actively harm
people besides. This is not a benign compound; it should only be taken when
you have a solid expectation of benefit, and (saying it again), we don’t yet
have that. Better trials are cranking up right now: please, wait for those.
The generic drug companies (Teva and Mylan, I’ve seen so far, and there’s
this) that are cranking up production are doing the prudent thing – if this
reads out well, we’ll need a lot of it. But we’ll need to give it to people
who are in bad shape from the viral infection, too, remember that, and I fear
that a lot of people around the world are just starting to take it now in
hopes of a prophylactic effect, which is (saying it again) a bad idea._

~~~
patrickbuckley
This is a great reminder, thank you for pointing it out. Interestingly during
the 1918 Spanish flu aspirin was a new drug and was given to people in an
effort to reduce fever. The problem is they gave it in doses that we now know
is toxic. There is some evidence that patients treated in hospitals with
aspirin had a 30x!!! deathrate vs those treated "homeopathically". This
YouTube video goes into the history and context of it ...

[https://youtu.be/dT6mHi_8V5E](https://youtu.be/dT6mHi_8V5E) (go to 11:30 in
video)

I beleive in modern medicine and science but we should be careful about being
overly optimistic and harming people by giving them a powerful drug that
hasn't been tested properly.

Edited to add time point in video.

~~~
mymacbook
Those that did not take aspirin during the Spanish flu had far lower morbidity
rates. Fever is not something I rush to suppress with drugs until I exceed
104.0 - same for my family and even when our daughter was a little tiny thing.

Preliminary unpublished information shows concerns on accelerating progression
of SARS-CoV-2 virus to COVID-19 illness for ALL NSAIDs (not just aspirin).
However, even with non-NSAIDs I exercise extreme caution when using (e.g.
acetaminophen - Tylenol - 4000mg is considered VERY TOXIC for liver).

------
stevespang
Derek's column does not ever post my responses (censorship ?) so here it is:

The side effects of chloroquine are modest for most, especially on a 10 days
or less regimen. Approx. 5% or higher risk of NOT taking it when ill from
coronavirus it is you could end up in ICU on a ventilator, on the other hand,
the risk of taking it and getting serious side effects is minimal, like at
about 1.5% in the study below.

Google this title: Reported Side Effects to Chloroquine, Chloroquine plus
Proguanil, and Mefloquine as Chemoprophylaxis against Malaria in Danish
Travelers

Summary: 85% of Danish travelers reported no side effects

minor side effects are:

Diarrhea, stomach pain (take only with a full meal), dizziness

the depression / anxiety incident was ONE person - - we don't base science on
what happen to ONE person.

severe side effects in only 1.5% of cases

Only LONG TERM USE for many months or years can have retina involvement.

So all those who want to bash the multiple recent published research results
showing good results with chloroquine and hydroxychloroquine for COVID19 - - -
maybe I'll read about you in morgue statistics somewhere soon. I have already
got my 'script for chloroquine (cost me 70 cents total), I am ready and
prepared - - - instead of being a naysayer with my head in the sand.

------
Munky-Necan
Until there's a double blind placebo trial I will take this type of report
with a truck load of salt. We want randomized control trials in medicine. We
want highly vetted research in medicine. Lacking either is a bad idea.

I am also not holding my breath about a vaccine. We tried making a vaccine
with SARS-CoV with a significant amount of the animal models dying from
cytokine storm after viral exposure. Drug trials are hard, but necessary.

~~~
icelancer
>> Until there's a double blind placebo trial I will take this type of report
with a truck load of salt.

You're welcome to. The remainder of the world should have the choice. Some
people can't - or don't - want to wait for an RCT with a sample size in the
thousands before taking a cheap and well-known drug with well-tolerated side
effects.

~~~
jki275
To be fair, I don't think that he's saying it should be banned -- he's saying
that we need a lot more testing before claiming this is a cure based on one
study with a tiny number of participants. His statement is accurate.

And the quinine derivatives have some very subtle neurological effects that
last a lifetime. Suicidal ideations -- for life and incurable -- are a well
known side effect of mefloquine at least. Maybe this one doesn't have those
effects, I don't know -- but there's a really good argument to do a lot of
testing before taking this in any other than an in-extremis situation.

~~~
Munky-Necan
Bingo, we need nonbiased blinded drug trials otherwise the data could be
seriously flawed. There's drug trials for reasons, and even in this pandemic
we should respect the rationale for why we established those trials.

Also, I'm finding that this forum is full of incredibly intelligent
individuals who demonstrate the a little knowledge is a dangerous thing. It
amazes me how often y'all will talk about medicine like you're experts but
miss fundamental concepts. May points, like the other poster, sound awesome to
lay people, but under the scrutiny of any medical professional would be
laughed at.

~~~
jki275
Dunning-Kruger is a thing unfortunately.

------
tibbydudeza
A vaccine was developed in haste for an outbreak of swine flu in 1976 (CDC
feared it was a repeat of 1918 flu) and about 45 million Americans received it
but 450 people developed GBS (Guillaine-Barre Syndrome) as a result.

Going on a hunch or unproven stuff is simply going to give the anti-vaxxer
idiots further ammo

~~~
ApolloFortyNine
Taking your numbers as fact, that would be a .001% death rate.

Coronavirus has a death rate ranging from .6-2% (overall), varying drastically
to upwards of 20% with age.

It's not a hard call to make.

~~~
wtallis
> Taking your numbers as fact, that would be a .001% death rate.

Death rate for GBS is more like 7.5%, not 100%. Though for today's challenge,
the relevant stat may be that ~15% of GBP patients end up needing a
ventilator. But even that wouldn't be a problem if we had such a vaccine for
this coronavirus.

------
aazaa
Only one clinical study has been published on chloroquine (by a French group),
and the results are lackluster. No patient was cleared of virus after six days
using hydroxychloroquine alone. A tiny fraction of patients were cleared in 4
days using an adjunct therapy (azithromycin). The study itself has issues, and
it's not even clear whether it will clear peer review.

The President is doing something very dangerous here with his comments in the
last two days.

By stoking chloroquine hype, he's setting the country up for a massive
disappointment should the drug fail to produce treatment, or unexpected side
effects.

Although the drug has been used in humans for decades to treat malaria, it has
not been used to any extent on humans to treat COVID-19. There's a non-zero
chance of adverse reactions, potentially serious given known problems with the
chloroquines.

Even worse, the idea that a "treatment" exists will encourage people to let
down their guard and will very likely lead to even worse outbreaks.

Unexpected things happen all the time in clinical trials. This is the main
reason it costs billions to bring a drug to market. We can't predict jack
squat.

~~~
Judson
Are you referring to this study?

[https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWS...](https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWSHnGbj/view)

Afaikt, 57% patients on HCQ alone were “virologically cleared” by day 6 and
100% on HCQ+Azithromycin were clear By day 6. Compared with ~12% of control
group.

~~~
aazaa
Yes, and I'm looking at the aggregate data in the last two graphs, and also
the big table.

HCQ + AZ was the only group with clearance for all after six days. It was also
the smaller of the two groups, which makes it hard to give any weight to the
finding. But there are many other features of this study that make the result
hard to interpret.

~~~
Judson
Great that we’re looking at the same study! I’m not sure what you mean by:

“No patient was cleared of virus after six days using hydroxychloroquine
alone.“

Because the percentages there are 57% Of patients on HCQ alone we’re cleared,
vs 12% control.

~~~
jschwartzi
Is there sufficient evidence in favor of rejecting the null hypothesis, that
57% of patients in the HCQ study group would have gone on to spontaneously
recover without HCQ? Because that's the really interesting question. It's not
a question of the study group versus control group, it's a question of whether
the study group and control group had enough characteristics in common to make
them statistically equivalent samples of a population that vary only in
whether they were given HCQ. And I think the consensus among people who are
clear on that is that the populations have too little in common.

~~~
Judson
A fair criticism of the study, but does not make the case that “no patient on
HCQ alone was virus free by day 6”, since that is objectively false by my
reading.

------
bpaddock
The Quinism Foundation Warns of Dangers from Use of Antimalarial Quinolines
Against COVID‑19.

"Use of Chloroquine, Hydroxychloroquine, Mefloquine, Quinine, and Related
Quinoline Drugs Risks Sudden and Lasting Neuropsychiatric Effects from
Idiosyncratic Neurotoxicity."

[https://quinism.org/press-releases/dangers-of-
antimalarial-q...](https://quinism.org/press-releases/dangers-of-antimalarial-
quinolines-against-covid-19/)

The Anit-Malaria drugs They are pushing have a common ancestor to
Fluoroquinolone antibiotics have MANY FDA warnings. The FDA says they should
not be used unless all other options have been exhausted.

Those that have already been devastated by Fluoroquinolones are extremely
upset to hear that a related quinolines drug is being proposed. While these
two drugs are technically in a different class, they share some common
ancestors. They both share many of the devastating side effects.

I have put all the FDA warnings for Fluoroquinolone antibiotics on my late
wife's website. Levaquin was a significant contributor to Karen's suicide. :-(

[http://www.kpaddock.com/fq](http://www.kpaddock.com/fq)

~~~
twomoretime
Respectfully, though I understand your effort to warn others, I think it is
dangerous at this time to conflate chloroquine derivatives with Chloroquine.
Single substitutions in biologically active compounds can cause drastically
different effects including substantially different therapeutic ratios.
Compare for example the various drugs in the amphetamine family
(methamphetamine, amphetamine, MDMA, etc). They are not equally dangerous.

Similarly, the terrible results you report are AFAIK rare with Chloroquine. It
is a well tolerated drug and if you're an older or immunocompromised patient
playing Russian roulette with a late stage COVID19 infection, the minimal risk
is highly preferable to no treatment.

