Hydroxychloroquine Update for April 6(blogs.sciencemag.org)
“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 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?
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.
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...
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.
Yeah, I'm a huge fan too. And this is a great summary and perspective.
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.
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
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.
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.
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...
Erythromicin and azithromycin can have a negative effect but supposedly the chloroquine ALSO can have an effect, so subbing in doxycycline will help but might not be enough.
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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.
In part there's a desire to tell people that we have "a cure" or "a vaccine" ready to go because it suppresses panic and anxiety by creating the impression that the problem is solved. Naturally, telling people that before it's actually true causes new problems, so now we have people fighting to combat misinformation.
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.
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.
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.
They'll spin the eventual deaths as inevitable and brag about how it wasn't 2x worse.
The original research paper circulating on Hydroxychloroquine was from Tom Broker. He was a student of my good friend's father at Wesleyan University.
Facts. Sad, depressing facts.
Because various high profile idiots have been lying about them. In an ideal world maybe this would be staying out of the public eye, but it’s a bit late to put the genie back in the bottle now.
Taking Chloroquine too soon might promote viral infection by inhibiting the anti-viral response. https://sciencedirect.com/science/article/abs/pii/S016635421...
CQ is for patients who have uncontrolled inflammation in response to the virus, not to be taken as a prophylactic.
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.
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:
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...
There is a clinical trial going on to check for just that. The hope is that when taken as a prophylactic it prevents entry into cells and give the immune system an advantage over the pathogen, but as you say, the immunosuppressive effects are a concern. We'll see soon enough.
Repeating myself, but: there's an extent to which that trial has already been running naturally, since lots and lots of people take doses of HCQ comparable to the C19 protocol already, for rheumatoid arthritis. Lots of those people are getting C19. Are you seeing reports that arthritic patients who get C19 are faring better?
I have not seen any co-occurence statistics. As both lupus and rheumatoid arthritis are at about 1% (each), and many of them are taking HCQ, then if HCQ works I would expect much fewer of them to be diagnosed with SARS-Cov-2 in the first place. This is something that the CDC _should_ be able to track, and doesn't even require any ethically questionable trials.
 and somehow the Lupus/RA mechanics are not influencing disease progress, which is not a trivial assumption, but does not disqualify the thought experiment entirely.
People with rheumatoid arthritis are not a good population to study. We know that certain comorbidities increase death rate. Now you have people with immune system problems taking an immunosuppressive drug. The outcome tells you nothing.
Jeremy Faust does not agree with you.
But it's still being given, so I'm certain there are other doctors still holding out hope.
He says "If it does work, it‘s not as good as you hope it is" and "STUDY THE DRUGS!" What he doesn't say is "lovely natural experiment" and "GREAT Stuff".
Are you seeing reports of the opposite?
Chloroquine is more toxic than Hydrochloroquine, isn't it?
IIRC the addition of the hydroxy to the drug means it's going to be more water-soluble so it would be easier to excrete in urine and flush it out of the system, which would count as "less toxic" if you squint when reading the paper
I haven't seen any detailed discussions of the differences in toxicity, but one physician made a comment to that effect.
You probably don't have to derive the relative toxicities axiomatically, since volumes appear to have been written about the lower toxicity of HCQ compared to CQ.
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-...
It’s a decades-old generic drug that multiple companies produce. Literally anyone with the means to do so can make it. There’s not a lot of money to be made with a drug that costs $5 for a course of treatment. You might have a point if he was pimping some brand new drug that cost $5000 a month.
Is it possible to corner the market on a generic drug that is produced across the world?
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.
Who says you need to corner the market ?
It's much easier to ramp up production than start an entirely new process with a new drug. And given we are talking about timeframes of weeks and months and not years all of the existing manufacturers will have a significant lead.
that wouldn't explain why Gov Cuomo is also a fan
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...
Let's see who will win.
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.
As opposed to Derek Lowe's "considered plan of treatment"?
As opposed to his decades of work in pharmaceutical-related areas of organic biochemistry, yeah.
None of which was in the proximity of an actual living, breathing patient.
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.
Regression to the mean is a huge problem with anecdotes. Some people get better. It may be due to some treatment, or they may just get better. This is why we have structured studies.
Yeah, I guarantee you that even with a 10% fatality rate 90% of people will get better spontaneously on their own. So any prospective treatment would have to do better than the recovery rate without treatment.
This is really a situation where the phrase "the plural of anecdote is not statistics."
Can you cite American clinical testimonials for HCQ? HCQ trials appear not to be controversial: they're being tried widely. Who's saying it's working?
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.
it mostly still does. You _can_ synthesize it but the yield's godawful.
Someone did the calculations. Ppl need to drink 200 gin tonics per day
Yes, but is there a downside as well?
Yeah alcoholism/liver/kidney failure obviously. It was meant as a joke
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-...), as does LA (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.
Substantial numbers of C19 patients are being given HCQ in C19 trials, but more than that, substantial numbers of newly-diagnosed C19 patients are already taking HCQ, since it's part of the standard of care for widespread conditions like rheumatoid arthritis. And those patients will of course have had the HCQ intervention before acquiring C19, not late in the course of their illness. It doesn't look like anyone is reporting unusual clinical success for those patients, while you can find clinical reports of QT disturbances (so: people are paying attention to this stuff).
Dosages for arthritis are pretty low, though.
Based on my experience, the standard dosage for rheumatoid arthritis is 400 mg/day vs 600 mg/day for COVID-19. To start with, anyway. I opted for 200 mg/day, and my rheumatologist concurred.
Dang. 400mg made me freak out. I have to take half that and can barley tolerate it.
Works great for my autoimmune condition.
What symptoms from it do you have?
I can only stand it at night.
Like drinking a double sized energy drink.
If I take it at night, I will toss and turn all night. Also a lot of vivid dreams.
>> a lot of vivid dreams
Remarkably, zinc sports supplement ZMA has the same side effect.
Looks like the C19 dosages are comparable to the standard arthritis dosages?
“You can do double blind studies until your patients are literally blue in the face, or you can try what works now.”
Linking to wikipedia articles about logical fallacies isn't a debate tactic.
> Kentucky is giving it to patients, too.
> Italy saw its numbers of deaths stabilize once they started giving it.
It appears the total number of cases also decreased. Which would suggest effect is likely due to social distancing.
> Marseille (where Raoult's hospital is) has the lowest fatality rate in all of France
Agree with you. There should be some kind of sanction for dumb posts that make claims without references. Downvoting isn't enough.
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.
> A healthy person taking a reasonable dose as a malaria countermeasure is not the same as a person on a ventilator in the ICU.
Well I don’t think a person on a ventilator is in any position to self medicate, a doctor who presumably knows what they’re doing would be the one to direct the course of treatment. What’s the problem with that? There’s literally no “established” treatment for Covid 19 other than “hope we can keep you alive long enough for your immune system to beat it”, so under a doctor’s care I really don’t think there’s a lot of downside to trying to establish the efficacy of certain drugs in lieu of a long trial process.
Is it being used as a treatment for those already on a ventilator? My impression is that it is being used as a way to help prevent patients from getting to the point of needing a ventilator.
I should have been more precise - even if you're not already on a ventilator, your respiratory system is under some stress that isn't going to be equivalent to the experience of most people taking HCQ under normal circumstances. There are also various reports of COVID stressing the heart which is another potentially scary thing that could change the safety of the drug.
As Derek notes in the article, "Many people are saying that perhaps it will work best if taken early in the course of infection" - so at that point your lungs and heart are probably doing great, so the risks aren't quite as severe if we're talking about early intervention... but in the event that it doesn't help and your condition worsens, now you've got HCQ in your system getting up to its side effect business while the virus goes to town on your cells.
Ultimately if a doctor is prescribing this stuff as an early preventative measure or attempting to use it to help patients who are in bad shape, best of luck to them - I hope it works. But it's really depressing to see laymen telling each other that it's safe to just take this drug.
> 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
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.
> 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.
Being 70 years old and widely prescribed does not mean the function and associated risks of the drug are well-understood. I literally saw a physician mention today in a video ( https://www.youtube.com/watch?v=ILowf7Tw7QY ) that the exact mechanisms at work here are not fully understood. He explained a half dozen different things HCQ/CQ might be doing in this scenario that are all biologically plausible based on what we believe we know.
HCQ/CQ aren't unique in this either. Lithium is widely used as a psychiatric treatment and has been in use for a long time even though for most of that time period we haven't had a good detailed understanding of how exactly it works. Gaps in understanding like that can lead to disaster unless we apply enough caution to match.
Another way to put this: We know some things the drug does, but that doesn't mean we know the complete set of what it does. We know some of the side effects and some of the risks, but unless we have a complete end-to-end understanding of everything happening here there is always going to be a risk worth considering.
> It’s a well-understood drug
For treating the issues it was designed for. Not for treating COVID-19.
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.
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.
500mg of Tylenol daily poses a risk of liver damage?
Listed contra-indications for tylenol include:
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
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
But would Tylenol at 500mg daily be a good choice? That's what parent was giving as an example, not your overdose contra-indications.
We treat COVID-19-like illnesses with Tylenol all the time. We do not use HCQ in the same way.
I think we can all intuitively see the distinction in risk tolerance between table salt consumption and HCQ consumption.
> I think we can all intuitively see the distinction in risk tolerance between table salt consumption and HCQ consumption.
Good thing we have doctors that can decide the best course of treatment via HCQ then.
I completely agree.
> Good thing we have doctors that can decide the best course of treatment via HCQ then.
Except in New York.
Asked about the progress of the trials at his daily press briefing, Cuomo noted that state officials have allowed use of the drug hydroxychloroquine in combination with the antibiotic Zithromax in hospitals “at their discretion.” He said the federal government would increase supplies to New York pharmacies, but that New York has imposed a 14-day limit to protect the supplies for people who rely on it to treat other medical conditions. 
It would suck to be one of the 200+ people dying daily  who didn't have a chance to try this combination to save their life because of a 14 day limit.
Now try to estimate the risk of _not_ consuming HCQ when you have C19 symptoms. Armchair virology and statistical studies are fun right up until the moment you get dry cough and shortness of breath.
You mean, like, that I'll have an infarction because of Q-T disruption, probably won't do anything to ward off C19, and, if I'm dosing it "over the counter" "like candy", might not have even had C19 in the first place? Seems like I can distinguish the risks between that and table salt too.
> Peter Navarro
An economist with zero medical background who from media reports is fighting against Fauci on this issue.
Any hint of a cure will be taken by people as a reason to ignore social distancing and stay at home rules. Which will directly cause an uptick in cases and deaths. Hence we need to be very, very sure that any cure is a real one.
Opting to listen to Navarro over Fauci is a very odd choice.
Look, I get that certain discussions on this damn site resist dragging politics into it all, but this is pretty important: Navarro has nowhere near the qualifications that Fauci does and there is no reason to listen to him on this.
You're contributing to a larger problem with misinformation at a time when it's not needed. Listen to the medical professional, not the economist.
I think he's just relying on Navarro's reporting that HCQ is being used in NYC, which, it clearly is; it looks like it's being tried all over the place. You can probably safely quote administration officials on something that simple. If he quoted Navarro saying HCQ was working, that would be problematic, especially because it doesn't seem to be working.
I don't interpret the comment that way, but more power to you if you do.
Going on to note these places where it supposedly work(s|ed) is indirectly bolstering Navarro's status in a discussion where he shouldn't be involved, and more or less implying that it does work when it clearly isn't working as described.
> or you can try what works now
If you don't do studies, how else do you know if it works? Or what dosage? Or when to administer? Or downsides?
Any drug with a high efficacy should be seen in small sample sizes.
E.g. As a sample size of one, I know that consuming alcohol has a relaxing effect. And that's highly testable, one I wouldn't mind participating in.
If n=11 and there was no deviation from the normal expectation, it's possible that there was some undetectable effect, but it's far more likely there was no effect.
Yale School of Medicine is onboard with HCQ as well. I guess they're total schmucks over there, nowhere close to the genius of Derek Lowe, who's not even a doctor. /s
Why can't you people admit that Trump was right?