
Hydroxychloroquine Update for April 6 - hprotagonist
https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6
======
robocat
“hydroxychloroquine itself actually lowers the activity of the innate immune
system; that’s why people take it for lupus and for rheumatoid arthritis. Many
people are saying that perhaps it will work best if taken early in the course
of infection” (from article.)

Yet HCQ takes a very long time to act as an efficient immunosuppressant (1 to
3 months for Lupus) as per
[https://news.ycombinator.com/item?id=22798370](https://news.ycombinator.com/item?id=22798370)
which seemed factual; but anyone have references to how long HCQ takes to
become immunosuppressant?

Hydroxychloroquine has a long half life in the body, so you have to wonder
what effects there will be from using it, especially if it turns out to be
ineffective.

The original idea HCQ was useful was from long term users of HCQ, which may
have quite different biological effects from short term usage in reaction to
dosing.

Also perhaps Lupus has a confounding factor that makes Lupus sufferers less
susceptible to Covid19?

~~~
treeman79
I have Sjogrens. A cousin to Lupus.

One month after starting this drug I noticed a decrease in symptoms.

I stopped taking it for a couple weeks. Symptoms started again.

So works but is slow. The stimulant aspect however hits in an hour and last
all day, and into the next morning. And oddly seems have some viagra like
effects. I have to really be careful if I take other stimulants.

Antibiotics also keep symptoms at bay, but doctors won’t write script despite
success.

This drug does a lot to the body. Good and bad.

------
raphlinus
I'm a fan of this review, and of Derek Lowe in general. I especially like the
way he explains effect size and also the reasons why we have to be cautious
when looking at promising drugs.

Another take, by James Hamblin at the Atlantic:
[https://www.theatlantic.com/health/archive/2020/04/hydroxych...](https://www.theatlantic.com/health/archive/2020/04/hydroxychloroquine-
trump/609547/)

This is written for a more general audience, and is not shy about taking on
the more political aspects, including the clashing agendas of the people
promoting HCQ and those urging a more skeptical approach.

~~~
mirimir
Yeah, I'm a huge fan too. And this is a _great_ summary and perspective.

------
kevingadd
The possible high-mortality interaction with metformin is a terrifying
prospect. Diabetes is so common... hopefully it's something that doesn't apply
to humans.

~~~
buboard
In mice. Hcq has been around for a long time, you d think that if it was so
lethal in humans someone would have noticed

------
nwah1
Various doctors have been using chloroquine with high dose zinc. One idea is
that chloroquine is simply a zinc ionophore, and its other effects aren't so
relevant. Zinc has a long history of being recognized as an important nutrient
for the immune system.

[https://journals.plos.org/plosone/article?id=10.1371/journal...](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109180)

------
dmh2000
isn't it the azithromycin that causes the arrhythmia and i heard it is
recommended to use doxycycline instead for anyone vulnerable to that side
effect.

~~~
sunnyP
I just read an article where Dr. Mohammud Alam in Long Island is treating
covid19 patients that have heart issues with that combination.
[https://townhall.com/tipsheet/katiepavlich/2020/04/06/here-a...](https://townhall.com/tipsheet/katiepavlich/2020/04/06/here-
are-five-doctors-whose-patients-have-seen-recovery-with-hydroxy-
chloroquine-n2566409)

------
moron4hire
Why are we talking about drugs in the public media? This is like people
demanding certain drugs from their doctors because they saw it in
pharmaceutical commercial.

~~~
threeseed
Because it's actively being pushed by right-wing media and the President.

We have a Presidential election in November. And there is a proven, strong
correlation between the strength of the economy and your chance of being
elected. You can't have a strong economy and people feeling happy when they
are stuck at home without a job and fearful of leaving the house.

So they need to get people back to work. And the only way that happens is if
you can convince people that it's okay to get COVID-19 because there is some
magical drug that will cure you if you end up in hospital.

~~~
brandon272
That might work if the election was say, within the next 15 to 30 days. Trying
to scam the general population into believing that an unproven drug is some
kind of "magic" cure is an awfully bold and risky move 7 months from an
election, especially before a potentially staggering number of deaths has been
realized.

~~~
threeseed
Consumer confidence, unemployment rate and economy strength are all lagging
indicators.

People need to be working, shopping, socialising and the media reports of
death and despair completely over before everyone is going to feel happy about
the world. If we ended COVID-19 today it would take months for the negative
effects to wear off. Just look at what happened after 9-11.

There is a reason that the same right-wing commentators and Trump were so
aggressively pushing the "get back to work" easter timeframe and are still
talking mostly about jumpstarting the economy. Politics doesn't stop just
because of COVID-19.

------
pazimzadeh
Taking Chloroquine too soon might promote viral infection by inhibiting the
anti-viral response.
[https://sciencedirect.com/science/article/abs/pii/S016635421...](https://sciencedirect.com/science/article/abs/pii/S0166354216300237?via%3Dihub)

CQ is for patients who have uncontrolled inflammation in response to the
virus, not to be taken as a prophylactic.

~~~
hexl
If I remember correctly, someone on twiv's podcast said that the inmune
inhibition occurs months into treatment for lupus patients taking HCG. So,
Could you explain in layman terms why this is not the case? Most of us have no
clue about what's being discussed in the paper.

~~~
pazimzadeh
I haven't seen any evidence that (Xydroxy)chloroquine alone directly inhibits
anything to do with the viral replication. The closest thing that I found is
that Thymoquinone inhibits Mouse coronavirus replication and is generally
protective of lungs:

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933739/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933739/)
[https://erj.ersjournals.com/content/50/suppl_61/PA4935](https://erj.ersjournals.com/content/50/suppl_61/PA4935)

Chloroquine is an antipyretic and relieves symptoms like fever from diseases
like Malaria and dengue.

Chloroquine stops the inflammation from going out of control, which a good
thing during an infection. But if you take it when you don't have an
infection, it could stop you from detecting viruses in the first place.

The paper I cited in the previous comment mentions that Chloroquine is a TLR7
inhibitor. TLR7 is a receptor that senses of single-stranded viral RNA.
[https://www.sciencedirect.com/science/article/abs/pii/S01663...](https://www.sciencedirect.com/science/article/abs/pii/S0166354216300237?via%3Dihub)

------
ck2
While other drugs are looking far more promising, there might be an obvious
reason why despite lack of clear proof/results the president is pushing it so
hard like everything else that motivates him:
[https://lawandcrime.com/covid-19-pandemic/major-producer-
of-...](https://lawandcrime.com/covid-19-pandemic/major-producer-of-
hydroxychloroquine-once-paid-michael-cohen-hefty-sum-for-access-to-trump/)

~~~
Mountain_Skies
Is it possible to corner the market on a generic drug that is produced across
the world?

~~~
kevingadd
Given the widespread shortages of the drug, you could operate on a 'rising
tide lifts all boats' model here and if you're one of only 3 large scale
suppliers you know that you and your competitors will all be selling more
product.

I don't think it makes sense as a reasoning for boosting HCQ, though, and
there are more obvious reasons why he'd promote it. If you want to make money
this isn't how you do it.

------
m0zg
In the left corner we have Derek Lowe, who's not a doctor.

In the right corner we have the Yale School of Medicine which recommends HCQ
for both the mild and severely ill patients: [https://files-
profile.medicine.yale.edu/documents/7801c631-3...](https://files-
profile.medicine.yale.edu/documents/7801c631-3dcc-48fc-a438-3aa18f3b7130)

Let's see who will win.

~~~
zimpenfish
That Yale flowchat is basically "throw whatever we can at the patient and hope
that something works". It's not a considered plan of treatment that has been
thrashed out over years of trials and experiments.

~~~
m0zg
As opposed to Derek Lowe's "considered plan of treatment"?

~~~
zimpenfish
As opposed to his decades of work in pharmaceutical-related areas of organic
biochemistry, yeah.

~~~
m0zg
None of which was in the proximity of an actual living, breathing patient.

------
war1025
My completely anecdotal experience with the Hydroxychloroquine story is that
researchers keep pooh-poohing it and people in the field keep having success
with it.

All I know is that based on the aggregate of information I've seen thus far,
if I come down with Coronavirus, I want to be prescribed that stuff.

~~~
benjohnson
Quinine used to come from the bark of a tree - that bark is available as a
nutritional supplement. It's also is used to make the bitter taste of Tonic
Water.

~~~
buboard
Someone did the calculations. Ppl need to drink 200 gin tonics per day

~~~
microtherion
Yes, but is there a downside as well?

~~~
buboard
Yeah alcoholism/liver/kidney failure obviously. It was meant as a joke

------
m0zg
Counterpoint: [http://www.leparisien.fr/societe/sante/chloroquine-ne-
perdon...](http://www.leparisien.fr/societe/sante/chloroquine-ne-perdons-plus-
de-temps-l-appel-de-personnalites-medicales-03-04-2020-8293677.php)

You can do double blind studies until your patients are literally blue in the
face, or you can try what works now. That is literally the choice at the
moment.

According to Peter Navarro, a good percentage of NYC patients are getting HCQ
at the onset of symptoms now. Cuomo wants more of it, because it "appears to
be working". Oklahoma is giving it to patients, too
([https://www.news9.com/story/41972631/state-secures-
possible-...](https://www.news9.com/story/41972631/state-secures-possible-
coronavirus-cure-for-hospitals#.XotJyWjOGbE.twitter)), as does LA
([https://twitter.com/ABC7/status/1246998628331163649](https://twitter.com/ABC7/status/1246998628331163649)).
Italy saw its numbers of deaths stabilize once they started giving it.
Marseille (where Raoult's hospital is) has the lowest fatality rate in all of
France. If it works, we should see the recoveries shoot up in 5-7 days.

HCQ is also available _over the counter_ in some countries, and is given out
like candy all over Africa where there's risk of malaria.

~~~
kevingadd
The fact that you can buy the drug over the counter doesn't mean it's
universally safe. The people being hospitalized here are already doing poorly
so exposing them to additional risk is not something you should just do on a
whim. As the linked post mentions, there are clear signs of potential risks
associated with the use of HCQ. I hope for the patients being dosed with it
now that it both works and is safe, but it's incredibly reckless to go 'it's
over the counter so it's fine'. A healthy person taking a reasonable dose as a
malaria countermeasure is not the same as a person on a ventilator in the ICU.
Their immune system is in a different condition, so is their heart.

~~~
m0zg
> doesn't mean it's universally safe

_Table salt_ is not safe. Eat 100 grams of it and you will die. This does,
however, mean that it's not as "dangerous" as the mainstream press wants you
to believe. It's a 50 year old drug used all over the world. If it was
"deadly", we'd know it by now.

CDC itself recommends taking it _as a prophylaxis_ when heading to the areas
where malaria might be present:
[https://www.cdc.gov/malaria/travelers/drugs.html](https://www.cdc.gov/malaria/travelers/drugs.html)

~~~
threeseed
This drug is not administered to everyone though. It's only been tested and
verified for people with I believe lupus and malaria. So we don't know the
implications of rolling it out to millions of people worldwide.

That's why you do clinical trials.

~~~
xienze
> So we don't know the implications of rolling it out to millions of people
> worldwide.

It’s 70+ years old. It’s a well-understood drug. It’s an experimental
treatment, not an experimental medicine.

It’s also frequently prescribed to grandmas with rheumatoid arthritis.

~~~
threeseed
> It’s a well-understood drug

For treating the issues it was designed for. Not for treating COVID-19.

~~~
xienze
You could technically say that about Tylenol, but I doubt there’d be anyone
jumping up and down about how dangerous it would be for a Covid 19 patient to
take 500mg of it daily as part of a treatment regimen. There’s literally NO
drugs approved specifically for Covid 19, but there are drugs, like HCQ, which
are promising and well-understood in general.

~~~
kevingadd
Tylenol is an odd choice of example here given that it poses a risk of liver
damage and for some subsets of the population it's actively dangerous to take
it. We literally lace some drugs with Tylenol to make them "abuse-deterrent"
because we know taking too much of it would harm you.

~~~
Fjolsvith
500mg of Tylenol daily poses a risk of liver damage?

~~~
kevingadd
Listed contra-indications for tylenol include:

    
    
        caloric undernutrition
    
        acute liver failure
    
        liver problems
    
        severe renal impairment
    
        a condition where the body is unable to maintain adequate blood flow called shock
    
        acetaminophen overdose
    
        acute inflammation of the liver due to hepatitis C virus
    

Obviously doctors are experts and will make the right decision based on risks
and advantages, but tylenol is a poor choice of example for 'effectively risk-
free drug'. I've seen multiple people mention that their meds are laced with
it even though it's contra-indicated for them

~~~
Fjolsvith
But would Tylenol at 500mg daily be a good choice? That's what parent was
giving as an example, not your overdose contra-indications.

