Chloroquine, past and present | Hacker News Reader

Chloroquine, past and present

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261 pointsilamont303 comments

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 [2] https://scholar.google.fr/citations?user=n8EF_6kAAAAJ&hl=fr

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-...

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

https://www.reddit.com/r/medicine/comments/fkb0wa/university...

So true. I hope we could listen to real expert (like Pr Didier Raoult) instead of so called expert like this Derek Lowe (PhD in organic chemistry, he is no expert in infectious disease at all).

In France, when Pr Didier Raoult in 25th of February [0] said that the chinese found that chloroquine was effective like it is effective against SARS-CoV (2003) [1], it was considered a fake news by "Le Monde" one of the most read journal in France...

Only now, because he has published a study [2], people are starting to say: "may be we need to check further"...

Everybody was saying: "Yeah, but there is side effect". Their team has used this drug for decade and know exactly how it works and how to use it...

So people, please, please, let's the real expert do the talking.

[0] https://www.mediterranee-infection.com/coronavirus-vers-une-... [1] https://virologyj.biomedcentral.com/articles/10.1186/1743-42... [2] https://www.mediterranee-infection.com/hydroxychloroquine-an...

Presently, I would think fatality rates mostly measure testing penetration, not treatment effectiveness. A country that's testing everyone will show a much lower fatality rate than a country testing only the sickest people, because the latter countries have few to no confirmed minor cases.

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.

> 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.

No it's not very hepatotoxic, on the contrary.

"Hydroxychloroquine has not been associated with significant serum enzyme elevations during therapy of rheumatologic diseases. Furthermore, clinically apparent liver injury from hydroxychloroquine is rare. " https://www.ncbi.nlm.nih.gov/books/NBK548738/

"Despite use for more than 50 years, chloroquine has rarely been linked to serum aminotransferase elevations or to clinically apparent acute liver injury."https://www.ncbi.nlm.nih.gov/books/NBK548224/

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

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.

Fwiw, Plaquenil is hydroxychloroquine, a less toxic derivative of chloroquine. It has a different safety profile than chloroquine

The French study of HCQ had several limitations. Including that it was very small and some patients who got HCQ and progressed to go to the ICU were excluded from the study. Thus making the drug look better than it is

HCQ is not likely to be a miracle cure. It may be useful in combo with other drugs

It's easy to make not great data look like great data to untrained eyes. And it's tempting to cut scientific corners to bring forward a drug for covid-19. But if the drug doesn't work, we should be honest about that and look for better drugs

Should at risk people take HCQ as a precaution until something better comes along? Definitely. but we need to be careful in talking about its potential

> It may be useful in combo with other drugs

Weren't the first studies done in combination with azithromycin (which is bizzare, as that's an antibiotic)?

The azithromycin was given to some of the patients with viral pneumonia as there is a chance of reinfection with bacterial pneumonia. Astonishing and unexpectedly, the covid19 virus was completely wiped out in all the HCQ+azithromycin patients but only in a bit over half the HCQ alone patients. So just as an antiparasite drug surprisingly once was found to also work as an antiviral, azithromycin has unexpectedly been found to have some sort of a complementary amplifying or catalyzing effect with the hydrochloroquine. Of unknown mechanism and no doubt this will be explored in great detail in future research. For now it's known that putting the two together looks to be a good thing to do.

It may be early to conclude that azithromycin has a complementary mechanism with HCQ, the study was too small and there are too many confounding factors. It is possible there is some synergy but also possible that there is not

the problem is quite simple: the virus infects your body, damages your lungs, and fucks up your immune system. Then you get an opportunistic pneumonia

The mechanism is also quite simple: administer them both together and the antimalarials kill the virus, the antibiotics kill the pneumonia.

Azithromycin has been shown to have some antiviral effect though it has not been characterized and the mechanism of action is unknown.

I assume they chose that as a broad spectrum prophylaxis for and opportunistic concurrent infection but perhaps they chose it specifically for this reason.

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).

I would love to know where in the UK chloroquine is behind-the-counter and not prescription only.

Chloroquine is class P (pharmacy medicines), which is effectively "behind-the-counter but the pharmacist tells you how to use it".

The idea being that if you want to take a trip to somewhere tropical, you don't have to tie up a GP with a standard, low-risk medication, but it's not quite so low-risk that you just put it on the shelf. Behind-the-counter, if you will.

https://en.wikipedia.org/wiki/Over-the-counter_drug#United_K...

> Pharmacy Medicines (P) are medicines which are legally neither a POM or GSL medication. These can be sold from a registered pharmacy but should not be available for self-selection (although directions to discuss a 'P' product may be allocated shelf space with associated GSL items). 'P' medications are reserved from the GSL list as they are either associated with a need for advice on use, or used in conditions which may require referral to a medical prescriber. Suitable trained counter assistants may sell a 'P' medication under the supervision of a pharmacist and will ask questions to determine if the customer needs to be referred for a discussion with a pharmacist.

I’ve been trying to buy some since early January and haven’t found a single pharmacist who will sell it to me. If you know of one, please let me know.

No-one carries it because they'd have hydroxychloroquine instead. Hydroxychloroquine is prescription only.

You're not going to be able to get a registered professional to give you anything for off-label experimentation, especially not something with potentially serious side effects like chloroquine.

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

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.

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... . Here are the cardiology codes - https://myheart.net/cardiology-coding-center/coronary-interv...

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.

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.

No, the Stark Law prevents that (self referral, referring to another business the physician has a stake in) https://en.wikipedia.org/wiki/Stark_Law . Physicians are paid according to a fee schedule that decides how much each thing they do is worth. Each procedure or office visit is assigned a work Relative Value Unit, which is multiplied by a conversion factor ($36.0391 for Medicare) to determine how much a physician gets paid. Private insurance generally follows the Medicare RVU scale, and has an adjustment ~120-150% for the conversion factor (just a guess, only a student). This conversion factor was $36.6873 in 1998, so, adjusting for inflation, Medicare values each thing a physician does at 62% of what it did in 1998. I hate that most of my posts on this site are about this topic, but so many people on this site get it so wrong when it comes to how physicians are paid.

Had a week long freak out from it. Apparently mild stimulant can magnify if your on other stimulants.

Amazing drug otherwise. My autoimmune symptoms have greatly reduced on it. Wish I could take the full dose.

Heptatoxic: relating to or causing injury to the liver

For those not understanding the jargon (like myself).

Hepatotoxic is the correct word. Same root with the meaning liver for the words hepatitis and hepatology.

Please qualify the "very" in "very hepatotoxic."

I hear beer and wine are hepatotoxic too.

That's why I take milk thistle (silymarin).

I assume the Koreans are all taking silymarin with their chloroquine, which is why they aren't dying en masse from liver failure, right?

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

Also, for those considering to use the Cinchona bark itself as a prophylactic measure, as a natural / herbal / ayurvedic remedy, note that it also has potentially risky side-effects like slowing the heart, constipation and impact on the nervous system. In large quantity cinchona is UNSAFE and can be deadly. Symptoms of overdose include ringing of the ears, headache, nausea, diarrhea, and vision disturbances. Cinchona can also cause bleeding and allergic reactions, including hives and fever. It also interacts with a lot of other medicines like anti-coagulants, heart medicines, antacids etc. Be sure to check your medication list first.

Source: https://www.rxlist.com/cinchona/supplements.htm

COVID-19 is also hepatotoxic?

1. it's prescription only.

2. it's already available for compassionate use.

The FDA is allowing chloroquine and remdesivir to be used for 'compassionate use' to treat the coronavirus.

https://www.businessinsider.com/chloroquine-remdesivir-compa...

You don't need compassionate use for Chloroquine. It's FDA approved, so it's just off-label, which doesn't require any hoops, just a prescription from a doctor.

I take it for Sjogrens.

I have to watch does as it has a strong stimulant effect at times.

It is Life changing for me, but i was having a lot of severe anxiety attacks from it.

Dr doubled the doSe. Yea a week long freak out occluded before I figure out what was going on.

Still worth it. Just have to be careful

Great. I hope it becomes available to everyone.

"Novartis, Mylan and Teva to supply tens of millions of chloroquine tablets to fight COVID-19"

https://www.fiercepharma.com/pharma/new-commitments-mylan-an...

Might need to check for G6PD genetic deficiency before taking it though.

https://en.wikipedia.org/wiki/Glucose-6-phosphate_dehydrogen...

right. we need to wait for FDA approval. and since it's prescription only, you need to check with your doctor.

Doctors: "you need to wait for FDA approval!"

also doctors:

https://twitter.com/ml_barnett/status/1241172371404357633

https://twitter.com/JeffreyLowMD/status/1241172812762468353

https://twitter.com/amberwvzz/status/1241196003425992704

Dude. Chloroquine is FDA approved. Any doctor can prescribe it for any reason today. The drug company is not allowed to advertise or promote it for COVID without approval for that indication, but any doctor can prescribe it for COVID if in his/her professional opinion, it is appropriate.

Depending on the country, chloroquine (or hydroxychloroquine) are over the counter. At least it is in both the UK and India. The UK has banned export of it, and in India it's less prevalent than it used to be because of the spread of chloroquine-resistant malaria. It used to be used /extremely/ widely in places where malaria is a common occurrence.

The study from France seems to suck, though. Not very valuable data.

They measured virus, not outcomes, they measured virus in the throat, not the lungs, the starting point was not the start of the disease but some later (more arbitrary) point in time, the two groups were not randomly assigned and the study wasn’t really blind.

It could be that they just happened to compare two groups where the treatment group was further along in the illness – especially since they try to sell that as a disadvantage for them, but that could honestly be an advantage for them. We know that virus in the throat decreases as the illness progresses. (Virus in the lungs is much more relevant and also dangerous here, better would probably be outcomes.)

Not really evidence, sorry.

OP called it "quite flawed".

But it is most definitely evidence.

“Quite flawed” is wild praise for this trash.

I don’t think it’s intentionally bad but it’s still bad. In the end it’s easier to make things worse … and chloroquine could, we don’t know. So I wouldn’t touch it.

This article shares insight into how the virus progresses. https://www.theatlantic.com/science/archive/2020/03/biograph...

Insightful read in plain-spoken, non-specialist language! Thanks!

On the 26th February, in an interview, one of the researchers behind the French study said that he wasn't worried about Covid-19 and that it was just a flu...

Do you have a link?

It's all in French:

1st February: https://www.lejdd.fr/Societe/le-professeur-didier-raoult-ce-...

"This coronavirus isn't so bad"

26th February: http://m.lamarseillaise.fr/analyses-de-la-redaction/decrypta...

"The coronavirus isn't more dangerous than seasonal flu."

I wanted to write this comment. The researcher is indeed a specialist from what I read on the internet but given his total turn about concerning Covid I would personally not put any trust in his work. He participated in the crisis the country is facing right now, by saying on social networks there was no real danger about the virus.

I don't really get your point. He's indeed a specialist in infectious disease (he runs the most important infectious diseases lab in France)... but because his opinion on that virus disagrees with, what, hacker news, twitter and the mass media... then he's wrong? WTF.

In February millions of people were in lockdown in China and thousands were dying.

That's why it's difficult to understand how an expert could casually claim that this was nothing more than seasonal flu.

Scientists make mistakes. Scientists change their mind in the light of the evidence. Your distrust of this scientist is distrust of science. Please, don't do this.

What? There was more than enough evidence. They are the ones anti-science.

Not knowing the evidence doesn't make someone unscientific. Most scientists don't know most evidence.

If he had the evidence explained to him and then just assumed it would be different in France that would be unscientific, but we'd all need to read French to ague about that.

In February the situation in China was public knowledge.

It's difficult to understand why a country would go on lockdown and build emergency hospitals for something nor worse than seasonal flu...

Thanks, I've found it hard to understand the French study. Do you have a good link to an (English, sorry) summary or critique?

I don't know about the efficacy of Chloroquine in treating COVID-19 but I would imagine that we already know a lot about the safety of dosing people with the drug. Any one growing up in the tropics during the 70s or 80s took regular doses for malaria treatment. The main adverse reaction that often happened was a crazy amount of itching (it would last for 3 days and would not let up even when you were trying to fall asleep)

I remember taking malaria tables in preparation for a holiday trip to the tropics.

I would have been 12 or 13 years of age and this would have been in mid 70s.

As part of that same preparation I also had 2 jabs (I think for Yellow Fever and Cholera) and if I remember correctly I had to take one malaria tablet a day, for a period of two weeks prior to the start of the trip.

I honestly don't remember any side effects from taking those malaria tablets, but I do remember the 2 days of numbing pain in my arm, which I assumed was caused by the two jabs.

from what dr fauci said, they wanted to be sure there weren’t any adverse affects for people who already have covid. But that they know it’s safe under normal circumstances

> but at least data-containing study from France.

Are you are talking about the study that was trendy yesterday? The control group is not randomized, and most of it was in others hospitals. They are not counting the 6 patients that they lost in the treatment group (1 just leave, 1 had too much nausea, 3 where transfer to ICU, 1 die). It is more strange that they didn't lost any patient in the control group.

> 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.

For certain individuals who just happen to have a bad reaction, COVID could well be just as fatal as cancer. In terms of how fast it can kill people, in certain cases, it can be worse than a lot of cancers.

use hydroxochloroquine then?

Do you mean COVID is as fatal as cancer or Chloroquine is?

COVID. For >70 y.o. individuals mortality rate is 30%. If you're >70 y.o. have heart condition and have diabetes (all risk factors) COVID is clearly more deadly than some (most?) cancers, not to mention it kills in the order of weeks, when cancer kills in the order of months or years.

"For >70 y.o. individuals mortality rate is 30%."

Where are you getting this number? It is significantly higher than any I have seen.

https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm - TABLE. Hospitalization, intensive care unit (ICU) admission, and case–fatality percentages for reported COVID–19 cases, by age group —United States, February 12–March 16, 2020

https://www.worldometers.info/coronavirus/coronavirus-age-se... - Age of Coronavirus Deaths

https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm gives a CFR of 4.3–10.5% for age group 75-84 and 10.4–27.3% for age group ≥85. Your number is over that by quite a bit, where is it from?

Right. OTOH in the Chinese treatment guidelines, they say not to give it for >65 y.o. Unfortunately that's exactly the population it would potentially benefit the most. I'm guessing there must be some reason that's in there, but I'd like to see numbers.

Agree with all except wondering what you mean by the safety profile being not great?

It's been around for 70 years, taken by millions over very long periods of time with relatively minimal negative side effects.

Do you have sources for that? Would like to know the numbers.

Idk you could google it? But as anecdotal evidence I had to take it as a kid as a prophylactic against malaria. So did literally everyone I knew back then.

The half life is 2 months. Any bad reaction will linger.

Compared to antibiotics with a 8 hour half life.

Lets stay home instead.

>Lets stay home instead.

For a couple of weeks, fine. However on the other end of this spectrum is "Millions starve".

At some point we need to ask is that fair to the youth? (note: I'm an old fart)

Youth also doesn't want to deal with this disease. I'm 23 y.o., healthy as far as I know, but I still don't want to catch this disease. Why spend 2 weeks on the bed dealing with the worst flu, risk getting hospitalized? After all, even young patients can be hospitalized, even though fatality rate is lower. I vote everyone stay home for the time being.

Fine. But just be aware you may pay it with two years of unemployment. Or rather someone less qualified and educated.

they also don’t want to spread it to their parents or grandparents and kill them

>> Why spend 2 weeks

To acquire immunity while there are still hospital beds available in some places, in the unlikely event that you need one. That won't be the case a month from now.

How utterly and inconceivably selfish. How would that work out if everyone thought like that?

Is it really? I've heard there's some logic to this…

If instead, we all stay home and quarantine, the second we start reducing the quarantine the virus flares back up again. If instead, we start acquiring immunity in low-risk populations, at a rate that the hospitals can sustain, we'll have a degree of herd immunity and a portion of the population that can no longer spread it.

I'm certainly not an epidemiologist though; anyone smarter than me that can way in on that thinking?

> If instead, we start acquiring immunity in low-risk populations, at a rate that the hospitals can sustain, we'll have a degree of herd immunity and a portion of the population that can no longer spread it.

A fair portion of low-risk people will require intervention. Given that a lot more people are low than high risk, you're still overwhelming the health system, and all those low-risk people are still going to interact with others while they are asymptomatic but transmissible.

Delaying the pandemic buys time. Time is the most critically short resource.

Time means more ICUs, more ventilators. It means industrial capacity can shift from making consumer goods to medical supplies like masks. It means medical personnel get training and experience with the disease instead of shooting in the dark. It means labs and research teams can give more informed treatment advice.

It means small businesses and industries can try to reallocate resources and jobs and maybe save part of the economy. It means more time to educate the population to avoid high risk activities, wear masks, wash hands and so forth.

In every way it’s better if we delay the pandemic now that we know about it than if we just let it peak exponentially and kill the maximum number of people.

Studies show it wouldn't work if _everyone_ thought like that at the same time. But studies also show that you need to "pulse" the infection rate among low-risk populations in order to get past this in a controllable fashion by temporarily and partially lifting the restrictions on those people and letting them acquire immunity, while carefully isolating and supporting the high risk populations. The fundamental truth of the situation is: 60-70% will have to go through the wringer before this is over. "When", "which subset", and "how" will determine the fatality rate. One thing is absolutely clear: we _must_ completely isolate (and support) the elderly and those with severe pre-existing conditions. Large numbers of immune people could help with that. Complete shutdown of the economy (if such a thing were even possible) would condemn a lot of the vulnerable people to die, since they still need food and a lot of them also need medical care, which could become unavailable, like in Italy.

And if that wants to get organized I can see how that would work. "Get sick to beat the rush", however, is not that - it's an action where the only good outcome would be if only you do it, which I think is a definition of selfishness.

Thats fine, but as things are right now, we're short on beds in a few places, and are wasting beds everywhere else. Seems like a waste of the precious resources to me.

I'm a big fan of selfishness so I'll represent the 'that is just a bad idea' argument:

1) Such an individual would be contracting an unknown virus in an environment where hospital staff are the least prepared and practiced at dealing with it.

2) Such an individual is still exposing themselves to high risk of mistiming the outbreak and hitting it at the peak.

3) They might accidentally catch a different disease thinking it is COVID. Then if they got COVID they'd have 2 diseases; which is probably going to be quite bad.

If we all avoid getting COVID-19 for, say, another 2 months it is likely we'll have an available and effective drug for treating it. There are something like 5 different candidates I've heard of, so even if the odds of any individual one working out are <30% there is still a good chance there will be effective treatment by mid year. The contain, delay and avoid strategy really is a better bet.

> it is likely we'll have an available and effective drug for treating it

I don't believe this is likely at all. At best we will have something that kinda sorta works in some patients. If this was likely we'd have a drug for the common flu long time ago. To remind you, the flu takes about 50K lives in the US every year.

There are effective drugs for common flu strains; including a set of vaccines. And if the US manages to get COVID-19 related deaths down to 50k lives for 2020 that will be pretty peachy.

There won't be a vaccine this year. That's pretty clear. Vaccines take a long time to get tested under the best of circumstances. If not tested properly and administered to millions of people (which they'd have to be in order to have effect) they could cause a lot of adverse reactions and deaths all on their own. Don't take this as antivax bullshit: I do take a flu vaccine every year myself, including this year, my kid is fully vaccinated also (+ flu vaccine last year - I told him to "be a man"). It's just the nature of the beast - immune system can really fuck one up once it really gets going.

At some point it's not even fair to those most at risk for covid-19.

We're not even on the "couple of weeks" scale here. Unless we have a drug that can effectively treat coronavirus, we will have to shelter in place until a vaccine is available. 12-18 months.

When did we switch from 'flattening the curve' to 'trying to keep anyone from getting sick'? I thought we were mostly all going to get it this year, but we didn't want everyone getting it in a 1 month period?

Well, never, but we have 20 ventilators per 100k people, "flattening the curve" so strongly that we can treat everybody was always a bit of a pipe dream. You need to flatten the curve almost to zero to get to a "sustainable" level of disease. They are nearly the same goal. Any non-trivial level of disease that is not controlled will rapidly push you past the "flatten the curve" threshold. And we will certainly be here for longer than 2-3 weeks.

It is a little white lie that is important to tell the public to help build compliance, the lower you can push it the fewer people will die, but hospitals simply are going to be overloaded regardless. The choice we can make is one between "very overwhelmed" and "overwhelmed to the point of non-functionality".

"shelter for 12-18 months" is a little bit of an exaggeration but not much. Simulations suggest that after an initial harsh quarantine period (up to several months) to get transmission under control, we will need to shelter for about 2/3rds of the time (2 months on, 1 month off) for 12-18 months, and other measures for 100% of the time. The vaccine will be what finally terminates the situation. https://www.imperial.ac.uk/media/imperial-college/medicine/s...

Even then that may be optimistic (especially if the population is not fully compliant). Italy is not just working from home and social distancing, they are straight up quarantining everyone, and they still have overloaded hospitals and bodies piling up faster than they can cremate them. Presumably the quarantine will slow things down on the order of weeks to months, but right now things are brutal.

https://vimeo.com/398334975

https://mobile.twitter.com/foxmulder22791/status/12404540564...

The Chinese strategy of requiring everyone to get a phone app, to track them via GPS, doing widespread testing and then quarantining the people who have been in contact appears to be a much more effective strategy than blind quarantine or social distancing. No app, no uber, no groceries, no public transit, etc. The US citizenry absolutely will not stand for the mark of the beast though.

The Korean thing about masks and gloves probably helps too. Too bad the hospitals are down to about 11 days of masks let alone for the citizenry.

I'm not trying to be a downer but if chloroquine works that's a really fucking big deal, because that would give us a fairly straightforward alternative to treat cases or even prophylactically treat vulnerable populations. Unless you have a tool in your toolbox we are mostly just moving the deck chairs here and choosing between "really bad" and "oh shit".

The Chinese have an app for this? Why aren't we using that?

I'd happily be tracked 24/7, and I'm sure so would many many others, if it meant reducing the spread and getting back to some sense of normalcy a bit quicker.

https://twitter.com/CarolYujiaYin/status/1239583581325778944 (deffo not propaganda /s)

https://www.nytimes.com/2020/03/01/business/china-coronaviru...

The other thing is that other countries like Iran and Israel are just pulling the data directly from Google Location Services or from telcom location data. I assume the US will probably follow at some point, since that data can be accessed without a warrant since it's third-party-controlled data.

Thinking the entire world will quarantine for 12-18 months is a pipe dream. That will never happen.

US DHHS: "18 months or longer" https://int.nyt.com/data/documenthelper/6819-covid-19-respon...

UK government: "at least a year." https://news.sky.com/story/coronavirus-social-distancing-nee...

Modelling: "2 months on 1 month off until a vaccine is developed". https://www.imperial.ac.uk/media/imperial-college/medicine/s...

/shrug

It's unprecedented and I tend to agree with you that at some point the economic carnage is going to force alternatives, but right now that's the plan. Not the plan they're telling you publicly, but the real one they're planning for and reacting to.

At the end of the day if that's the plan you'll go along with it because the men with guns will make you.

As I've commented elsewhere, an approach using contact-tracing via app and GPS data, backed by widespread testing (millions per week) and small-scale isolation of affected, along the lines of China or South Korea, seems to be more effective.

https://twitter.com/CarolYujiaYin/status/1239583581325778944 (deffo not propaganda /s)

https://www.nytimes.com/2020/03/01/business/china-coronaviru...

The US population is going to hate hate hate that one. But it's that or stay inside except for going to the grocery store for the next 12-18 months.

If we don't choose option A, and we don't choose option B, we implicitly choose option C: 20% of our seniors die in a single year. Choosing not to choose is still making a choice. I believe there's a song about that.

http://www.euromomo.eu/

The all-cause mortality rate in Europe has been dropping in the past few weeks and is now well below normal levels. To me this looks like people have been overdoing the whole stay indoors and avoid any sort of risky behavior.

> "To avoid a rebound in transmission, these policies will need to be maintained until large stocks of vaccine are available to immunise the population – which could be 18 months or more"

That sounds very much like a "worst-case", afaik German CureVac are right now in the stage of selecting the last 2 candidates for a vaccine, they expect first clinical trials around June/July, I'd be surprised if they are the only ones that far along.

That's not meant to say this will be over the instant we have a vaccine, but finding one is right now the big X factor that makes all estimates veer on the rather pessimistic side.

How would this be possible without severe consequences to everything else?

I'm already locked up (Italy). I'll go insane, seriously, if I need to stay shut in for 18 months.

The recovering youth are getting breathing problems that aren't going away as well. It would be in their interest not to get it.

It's also resetting our global warming clock. Something youth were keen about getting the world to do. If they can't handle staying at home for an extended time then global warming might not be that important after all.

This isn't resetting the global warming clock. Atmospheric CO2 is still going up not down. It's a temporary and small reduction in CO2 output coupled with a much more severe and much longer term reduction in scientific output that might actually solve global warming, and a much longer term and much more severe economic recession that limits our options to (further) hurt the economy to switch to greener means of energy production.

Agree. This will ultimately be horrible for the environment. Environmental regulations will fall by the wayside and look at the price of oil.

Not sure you can have it both ways.

Either shutting down all Chinese factories for a period of time reduced CO2. Or they made no difference and we can run those factories without fear.

Wouldn't a global recession/depression reduce production?

Increased funding for scientific output or more climate models isn't going to make a difference. People have to buy and use less. You can't have it both ways here either.

If we set the rate of increase of atmospheric CO2 to 0, a far greater reduction than actually occurred, we would be pausing the clock on global warming, which is a very far cry from resetting the clock. Yes, the emissions reduction helped, but not a fraction as much as you claimed.

> Increased funding for scientific output or more climate models isn't going to make a difference. People have to buy and use less. You can't have it both ways here either.

The science I'm most interested in isn't climate models. It's better solar panels, or better wind turbines, or better batteries, or better fission reactors, or (useful) fusion reactors, or space based solar shades, or ways to remove CO2 from the atmosphere, and so on.

People buying and using enough less unfortunately does not seem to be a realistic solution to the problem. People buying less might be able to delay us hitting disastrous amounts of warming by a few years, but that only buys us time for the above kinds of research.

Aren't virologists predicting that 60-70% are going to get it, no matter what? What is the "extended time" that you are talking about?

Close to half of COVID infections result not even in a cough. Going by the mostly elderly population on the Diamond Princess, mortality with proper treatment is going to be significantly lower than 1%. Flatten the curve? Sure, but we can't be locking down the entire country indefinitely.

The youth already begrudge the elderly, locking them down for months will make them wish they were dead. Remember how a year felt like an eternity when you were 16?

Also, most youth don't care about global warming either. They're just virtue signaling. It really isn't that important, if they understood what they would have to give up on to stop it, they would embrace it and look forward to spring break in North Dakota.

> Close to half of COVID infections result not even in a cough.

Possibly?

> Going by the mostly elderly population on the Diamond Princess, mortality with proper treatment is going to be significantly lower than 1%.

If we're all sick at once can we all get proper treatment?

We're all making assumptions and treating our ideas like they have to be true. We still don't actually know, we will only know in retrospective, and that's important to keep in mind. We can't know what's going to happen, and I think we need to be more cautious than optimistic. Where's the line between that an insanity? I don't know, but we can't act like we know the math, especially when we're getting equal and opposite information every day.

We actually will not know even in retrospective, because the alternative scenarios will not play out.

I am not saying everyone should get sick at once, a certain period of isolation is acceptable - for now.

In the long term, it is not reasonable to isolate everyone. Covid-19 will stay with us for years.

Any avenue that could save lives is worth investigating. It's not an either/or situation.

Stop spreading FUD

OTOH that also means that the doses being used aren't as much higher than the prophylaxis dose as they appear. If you take it regularly, even at low doses, it builds up.

I'm all for staying home for now, but at some point we will have to come out, and we need something to help those that are already infected.

If CQ works as prophylaxis, we could potentially have a sort of interim herd immunity by having large portions of the population that could tolerate CQ taking it prophylactically while we wait for a vaccine. This is basically the current approach in regions with a lot of Malaria, and they've been waiting for a vaccine for a very long time.

The danger of course is SARS-CoV-2 developing resistance to Chloroquine as Malaria has. We need lots of people working as fast as possible on a vaccine.

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.

Supply is not an issue: https://www.fiercepharma.com/pharma/new-commitments-mylan-an...

We need testing that the medical community will accept.

> 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.

You shouldn't be getting it. It's prescribed in most 1st world countries.

It should not be used as a prophylactic at this time.

Its use should be prescribed and monitored by a doctor.

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

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.

That's false.

Potential Coronavirus Treatment Touted by Trump Already in Shortage, Pharmacists Say

https://www.nytimes.com/reuters/2020/03/19/world/asia/19reut...

Even if true (I don't really believe it), very temporary.

The article I cited suggests 200 million doses are on their way.

> I don't really believe it

That's strange.

It's perhaps worth noting that the two main points made in the two separate articles - that roughly 200 million doses will be available at some indeterminate future date including 130 million from Novartis if hydroxychloroquine is approved for treatment of COVID 19, and that the currently unfounded hype surrounding hydroxychloroquine has caused an immediate problem for some currently prescribed patients and four out of eight licensed manufacturers are in shortage - are not at all contradictory. I would not want to be one of the patients currently dependent on that drug right now.

I do appreciate your pointing out to another poster that they shouldn't acquire it without a prescription and a real need. I would think what was said might be a clue to you that the shortage the NY Times was talking about is more than plausible. People are not (forgive me for stating the obvious) fully rational or thoughtful of their fellow man when making their purchases lately.

Looks like they are!

"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."

Mostly it is a tiny tiny little fraction of the economic cost of a prolonged lockdown.

> 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.

I don't think folks are reading the whole article.

I'm not suggesting immediately starting to dose millions of people with it. I'm suggesting massively ramping up production so that if it turns out to be useful, we can at that point immediately start dosing millions of people with it.

I think it likely that the cost of massively increasing hydroxychloroquine production would be a drop in the bucket compared to the total resources being spent on tackling the crisis. So even if the drug turns out to not be effective, the attempt to mass-produce it would still have been a rational gamble.

Note that if hydroxychloroquine is not effective, your production facilities will be tied up if you do find something else that is effective.

But won't they be tied up one way or another producing something else, unless by chance they happen to currently be producing something that turns out to be important in the fight against the pandemic?

Not really, you just switch in the same agile manner you did to produce quinine...

I have a feeling things are about to come up roses for President Trump yet again! :-)

Stop making shit up, you have no idea what you're talking about.

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/

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

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

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

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.

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.

Quinine hasn’t been used for malaria prophylaxis since the times of the British Empire. Even for its successor, Wikipedia has this:

> Areas of the world with chloroquine sensitive malaria are uncommon.[84]

The overlap between countries with few cases of Coronavirus and those with Malaria is tenuous at best. Turkey doesn’t have Malaria, and for that matter neither does Russia.

People in Malaria areas also tend not to use pharmacological prophylaxis, because the side-effects are impossible to tolerate in the long term. Prophylaxis is for tourists. That’s why mosquito nets are such effective intervention.

How are you making the tonic?

Lmao.

I'm not a doctor (yet) but I believe quinine has immunosuppressant effects so you don't want to take it preemptively, only when you have your own immune system in overdrive.

that's been asked in literally every thread that has discussed this and no, modern tonic water is not as strong as the stuff the british used to make and is not an effective dose for either malaria or covid. You'd need to drink 30 liters or so a day to get a single dose, you'd kill your kidneys first.

tonic syrup/concentrate, maybe.

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

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.

"One that I find particularly amusing, for personal reasons, is the idea of complexing zinc ions...So yeah, I can at least believe that these things complex zinc, for what that’s worth."

Not sure if this statement supports or refutes your theory; I'm inclined to believe the latter.

Interesting! Could not find the part of the video where the claim is made. Can you help?

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.

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.

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.

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?

Moreover, please assume you're still shedding. You may still be contagious.

That's like me, and I haven't taken plaquenil or anything at all. Just got a weirdly sore throat yesterday, a very slight fever, a bit of a woozy head. Ten hours of sleep later and the fever went away, but I'm not stepping outside.

There's a word for it, and the word is anecdata. You can trust anecdata about as far as you can throw them.

You can get an antibodies test that you can do at home with a finger prick. Need to google it. I am about to one since I had symptoms couple weeks ago after being in the same room with someone with an uncontrollable cough.

> You can get an antibodies test that you can do at home with a finger prick.

Here's a recent discussion on $15 kit for SARS-CoV-2 serological test: https://news.ycombinator.com/item?id=22641946

iirc, Singapore announced a plan to do these tests to find total infections.

Many Covid-19 cases are mild even without any medication. That is an interesting anecdote though.

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?

> 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?

The term is "compassionate use". It's drug approval for patients where the drug is not fully tested.

It almost certainly wouldn't be approved for healthcare workers, but it might be approved for people who need ventilators.

The basic idea is that the situation is so dire - all of the normal medical options have been exhausted - that patients are legally allowed to essentially experiment on themselves.

These are approved drugs so the use would be "off label". Doctors are allowed to prescribe anyway they see fit.

The main dangers for the general public are the acute toxicity and drug interactions. Take chloroquine, which comes in 500mg tablets, it does not take many tablets to get to toxic or even lethal dose. The drugs can prolong QT intervals, so combination with other drugs with similar side effects like some antibiotics or antidepressants could be dangerous.

I have 250mg tablets. I also have bisoprolol to counteract prolonged qt interval. Be prepared :)

You may be interested in this study then: https://www.ncbi.nlm.nih.gov/pubmed/32150618

Note in the full text article they show simulation of how long it takes for the drugs to reach therapeutic concentration at the lung. Since we don't know exactly where the antiviral effect comes from, these are only guess works.

It's a misdirection of resources - of money, clinicians' time and study subjects. There's enough drug and patients to run a well-designed clinical study, once that is done we know if chloroquin is any good or if we need to keep looking. My guess is that we are better off looking at antivirals.

No. Because that vast majority of cases are mold or asymptomatic.

"mild" means "you probably have pneumonia, just not bad enough that it could suddenly kill you, so you don't need to be in the hospital (yet?)"

Not the GP, but "mild" probably actually means mild. Given that only (highly) symptomatic people are tested, we don't know how many people contracted the virus and only had mild cold symptoms. Developing pneumonia would already put you outside of that "mild" designation.

We have a pretty good idea in Italy how many cases are asymptomatic or very mild and it is enormous. Traveling right now but if you are interested I'll update tomorrow

Yes, please.

https://www.sanitainformazione.it/salute/scovare-i-positivi-...

In English:

https://mobile.twitter.com/andreamatranga/status/12397748625...

> According to Crisanti, the director of the virology lab of U Padua, as little as 10% of #COVID2019 carriers show any symptoms at all. He sampled repeatedly the entire 3k+ population of Vo ', one of the initial clusters.

https://grapevine.is/news/2020/03/15/first-results-of-genera...

> 700 have been tested. Kári says that about half of those who tested positive have shown no symptoms, and the other half show symptoms have having a regular cold.

https://www.repubblica.it/salute/medicina-e-ricerca/2020/03/...

> "The vast majority of people infected with Covid-19, between 50 and 75%, are completely asymptomatic but represent a formidable source of contagion". The Professor of Clinical Immunology of the University of Florence Sergio Romagnani writes

In the discussion of the study over on Reddit, there were anecdotes of physicians prescribing hydroxychloroquine for themselves and their families, in enough numbers to make it difficult for patients previously prescribed it.

https://twitter.com/ml_barnett/status/1241172371404357633

https://twitter.com/JeffreyLowMD/status/1241172812762468353

https://twitter.com/amberwvzz/status/1241196003425992704

From a convo with a pharmacist friend:

> This is 100% true and I hate doctors for it

> Record today was for 360 tablets with 2 refills, please fill them all concurrently, they'll pay cash

> 2nd place was an out-of-state opthamologist who couldn't spell it or provide proper dosage

> Md's are being real dicks around here

> Keeping in mind it's a necessary medication for people with lupus or arthritis, too

> It's an anti-malarial that treats rheumatism

> It's not crazy expensive or anything, but it's not something you keep lots of on hand

> So these md's trying to start a run on it are being shitty to the point of unethical

> I asked the opthamologist for their npi/dea so I could try to report them to some kind of body, but he hung up

> I'm legit furious about it

Sure, but what is rational and what's allowed by the FDA are entirely separate things.

I expect to see a lot of exploring of this outside the US. Maybe once bolder countries have sorted things out, we can use their findings.

The FDA has investigated Plaquenil and there is a clear record of the side-effects and directed usage - I don't know why you think it'd be any sort of impediment.

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.

Permanent blindness typically takes many weeks / years of use.

https://www.webmd.com/drugs/2/drug-8633/chloroquine-oral/det...

Which might be necessary for prophylactic use.

You only need to mitigate the peak of infections from this virus. And I don’t think anyone is suggesting it to be used as a preventive tool. It is to reduce the contagiousness of people tested positive (and hopefully also help them with the virus).

No, the course is 10 days IIRC.

> The possible side effects include permanent blindness.

Yes, but only with massive doses or when treatment lasts for more than 5 years.

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

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.

Because blindness is a harsh outcome, so it jumps out and causes an emotional reaction.

The half life is 2 months. That's crazy.

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.

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.

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.

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.

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?

In the case of the french study, the timing is a key thing. Lower viral load quickly = less contagious = inserting grains of sand in the propagation of the virus and if the numbers add up, hopefully a non-economy nuking alternative to lock downs.

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

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?

Here's a short paper on it [pdf]: https://www.jstage.jst.go.jp/article/ddt/14/1/14_2020.01012/...

Not many details, just that it worked better than some HIV antivirals. Still, worth ramping up production of this in advance of trials. It's a surprisingly small and simple molecule.

This came out about an hour ago https://youtu.be/hPz5KxgI_K4?t=245

I was intrigued by the results from the recent quick french study: https://www.mediterranee-infection.com/wp-content/uploads/20...

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!

There is a long discussion about this study with the virologist Christian Drosten on a German podcast (transcript here: https://www.ndr.de/nachrichten/info/coronaskript134.pdf), though in german only.

He was quite skeptical about the study, in particular as it doesn't have randomized groups, and e.g. the age difference between control and treatment group was very large. He also didn't consider the virus concentration in the throat to be a good endpoint to measure as from their experiments they know that it goes down over time anyway, and the virus tends to move to the lungs.

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.

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.

As I understand it - it interferes with mRNA transcription. Given that COVID-19 is RNA that may be useful.

The study wasn't randomized. It tells you basically nothing.

I really don't understand why anyone approves such studies. They could've done something useful and we'd know a little bit now.

to the best of my knowledge, there has been no randomized study against placebo of several important things - like parachutes.

Next time I am in a burning plane, I'll make sure to refuse a parachute, as the lack of studies means anecdotal evidence tells us basically nothing.

You may want to read this: http://cmajopen.ca/content/6/1/E31.full

I don't know if Chloroquine works, but I'm pretty sure Chloroquine is no parachute (i.e. it's not a drug where the benefits are so obvious that it doesn't need a proper trial).

Nice article, thank you. Still it doesn't adresse the question: statistically, the benefits can sometimes be so obvious that no randomized trial is needed. RCT and large series are needed when trying to prove some minimal effects. The article is more like a sociological study to say invoking this parachute argument is no definite proof based on cases where the parachute argument was invoked and in retrospective was misguided.

That is very true. But unless we are to argue that the virus is not what causes the disease, using the viral load as a proxy for clinical status and contagiousness is acceptable. And unless the effect is small enough that sample selection can affect the conclusion, it doesn't matter much in practice.

I meean, for chloroquine, we have studies showing non inferiority and strong effects. We will not know if it works according to modern standards of statistics using direct survival statistics for another two weeks at best. What to do in the meantime?

In this article, the comparison to flossing in the intro is not good: lack of flossing does not entail mortality rate >.5%.

And all the other approaches selected for study do not feature infectious agents creating a risk of death, so the conclusions of the article are not very transposable to the problem here. For chemotherapy, surgery, etc. yes, they have a point. For microbiology, no.

Everybody seems to be doing armchair critique of the methodology used. I respect the desire to understand, but I believe the critique stands: we do not have RCT for parachutes. And at the moment, we do not have RCT for chloroquine either. We have a long experience of using it for other diseases. It's an old drug with well known side effects and toxicity.

If you are infected, you are free to wait until there is a trial to accept the drug. Yet, based on the information available, I still think it is a wrong decision, akin to asking for a RCT on parachutes aboard a burning plane.

> but it's something!

And that something may turn out to be noise.

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.

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

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

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.

Mixes well, only minimal brain damage ;)

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?

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.

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.

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...

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

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

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.

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.

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.

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.

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?

There was this medical person on the white house press meeting yesterday and she said that the WHO test had terrible false positive rate (she said 45% but that doesn't sound right)

The problem is not the CDC developing their own test.

The problem is their banning the use of other tests for months!

Only by Dr Helen Chu finally ignoring that ban was the Seattle outbreak discovered.

They should have been developing more than one test anyway. This reduces the risk of failure, and if you get multiple working tests, it allows some cross-checking to reduce false results. Failure to diversify is also mismanagement (though clearly more money can help you try more things).

I don't agree at all. The WHO had a working test. We just needed to produce as many of them as we possibly could, and send them to labs to set up and validate.

They needed every resource they had going to the confirmed working test. Even if the CDC was better funded, they still would have needed to spend every resource on that.

> There's still no explanation (afaik) for why they rolled their own test instead of using the WHO's test

The explanation is obvious, isn't it? "We thought our test would work, and it would be better."

It was stupid, to be sure. It would have been a stupid risk even if it had paid off—although in that case, few would be chastising them, and many would be thankful.

Agree, and that's kind of my point. Being "fully funded" wasn't the problem--it was hubris/mismanagement.

So, I think this is the most frustrating part of living in this political era. I did start this off with "funding", but it wasn't just funding, it was cutting qualified staff. It's that even the best qualified staff aren't moving fast enough or adapting and looking at cases beyond our own borders. Even in a reduced regulation environment, the FDA is likely hampering response time.

The US has regressed to an early 19th century model of government (loosely federated) at a time we're more tightly coupled than we ever have been due to moderinity.

>> fully funded CDC

Is there evidence that more money would have solved the constant CDC problems and incompetencies that are coming up? It seems like a throwaway obvious statement, but plenty of government agencies - and private companies - don't operate a lot more effectively with more money.

Totally agree, and in one of my other responses I recognize the shortcomings of how I put it. Thanks for the good faith response.

with more money, the CDC would not have delivered one non working test, but like 2 or 3 non working tests.

Bingo. On Feb 18, China released the 6th edition of its treatment guidelines that included a Chloroquine recommendation. They've subsequently updated that guidance to reduce the dose

On Feb 19, Chinese authorities published this paper: https://www.ncbi.nlm.nih.gov/pubmed/32074550 which provides basically no details except that Chloroquine works.

Everyone who was paying attention saw this. The U.S. gov should have started ramping up production at that time, but four days later Trump tweeted "The Coronavirus is very much under control in the USA... Stock market starting to look very good to me!"

It's more than the rumour-mill. There was a scientific study with a small number of patients that showed clear results, and several countries have now launched larger studies to confirm those findings.

No, that's the rumor-mill, spreading the preliminary results as if they were a confirmed cure.

The rumour-mill is that it _will_ prevent or cure.

As you've said, studies are still being conducted. I've read the original chinese study and it's promising, but there's still work to be done.

Also, Bayer thinks there's enough merit to this to issue their own press release and donate 3M pills.

"New data from initial preclinical and evolving clinical research conducted in China, while limited, shows potential for the use of Resochin in treating patients with COVID-19 infection.

Bayer in recent days has been in talks with the White House, HHS, CDC, and the FDA, offering any assistance we can provide with a focus on donating Resochin to help in the government’s efforts to combat the virus.

Currently not approved for use in the United States, Bayer is working with appropriate agencies on an Emergency Use Authorization for the drug’s use in the U.S.

Bayer thanks the Trump administration for moving quickly to enable this donation and will continue to work closely with the administration to support its efforts in the fight against COVID-19."

https://bayer2019tf.q4web.com/news/news-details/2020/Bayer-P...

An optimist would say this is Bayer being benevolent, a pessimist would see this as them taking advantage of a situation to make a lot of money out of a possible snake oil during this time of panic.

We stocked up on my daughters medications last week, there was already a non-covid-19 related shortage. Thank god we got what we need for several weeks. Its pretty scary when you rely on a common drug and it runs out.

Reminds me of a comment I read on Reddit some week ago; the commenter was going from store to store looking for disinfectant for a family member that has a prosthetic and needs to disinfect it daily, lest an infection gets into the wound.

Those tiny square alcohol prep pads (e.g. for diabetics and others who need daily injections) are sold out everywhere. I suspect people who couldn't find hand sanitizer or Clorox just grabbed whatever sanitizing products they could.

I clean stuff with them. I don’t want water and some antibacterial agent, I just want some nice alcohol.

When there is not a pandemic happening you can get 99% isopropyl at a reasonable cost. Its great for cleaning electronics and lots of other things.

Yea, my wife takes plaquenil to treat arthritis and I asked her to double check her supply when these rumors started floating around. It's always scary to imagine a bunch of folks going out and hording the stuff to scalp it off later.

I bought aquarium chloroquine to use as a last-ditch resort if I basically have to choose between taking it or dying due to hospital overcapacity. No harm to patients there IMO. I spent $60 for the 10 grams recommended for a course (.5 g a day). That was last week, and it's so much more expensive now.

Is there any difference in aquarium cloroquine and prescription? I’m assuming mostly manufacturing conditions

How do you plan on measuring your dose and dosing it?

Do you have a source for it? I've had to buy through underground labs; could not find any Avaclor.

I really hope this virus prompts our disaster management agencies to get their shit together, and specifically to consider supply chain security as part of their threat model (and no, we don't meaningfully do this or we wouldn't have such a pitiful national reserve of respirators and other respiratory treatment devices following SARS and MURS). Not sure exactly what this would look like, but identifying key partners in industry and working with them to enable them to turn-key ramp up production seems obvious.

How could our disaster management agencies have gotten their shit together to anticipate a run on an old anit-malaria drug?

Optimize for the aspects of the supply chain that don't depend on the specific drug. For example, the packaging of pills probably doesn't need to vary that much in general.

But the point isn't that we are prepared for every eventuality (e.g., chloroquine), but that we are doing due diligence in preparing for the likely eventualities (e.g., general purpose respiratory treatments like ventilators).

As a previous commentator noted, the Chinese were providing guidance on chloroquine a month ago.

How to people get it? I assume it’s a prescription drug everywhere? Is everyone friends with a doctor or is my expectations on doctors too high (that they shouldn’t prescribe something just because a patient asks for it, perhaps especially not if the patient asks for it)?

I bought chloroquine few weeks ago when there was still plenty of it. A week ago it was out of stock not necessarily due to rush buying but because government bought out all the stock to give it to hospitals to use if it turns out to be effective.

You must see my family whatsapp group ... all sort of weird folk remedies and weird home made concoctions (usually harmless involving mixing garlic and flu medicine) to protect against this new virus.

I implore you to make a post on HN if you run out. From reading posts on HN I would suspect many have bought it online and may be willing to do the right thing and mail it to you.

In Norway it has been restricted after doctors prescribed lots of it for themselves... Way to undermine the efforts.

How is this possible? It requires a prescription, no?

SMH...

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

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

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.

This snippet right here does a good job balancing optimism with caution. We need more of this.

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 (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.

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).

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.

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.

>> 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.

Do no harm. This is the first line for a reason and when we deviate from strong evidence we will always find regret. If you've talked with your physician and understand the risks, be my guest.

Until we've done a double blind placebo trial we won't even be able to demonstrate efficacy.

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.

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.

Dunning-Kruger is a thing unfortunately.

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

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.

> 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.

That's a pretty good rate, ~10x GBS than you would expect deaths from regular flu.

GBS is listed as a side-effect of UK's Fluenztetra flu shot IIRC. Most people reportedly fully recover from GBS.

I don't think even a scientific study would be effective against odds as small as 450 out of 45 million. Vaccines are tested by hundreds, or thousands of people before mass produced. Catching an event as unlikely as this doesn't seem possible. One would hope animal models would be helpful, but what if vaccine only causes GBS to humans?

I suspect people who don't understand vaccines may have reflexively downvoted your comment but in fact this is a real risk. There is also concern over repeating the debacle with the respiratory syncytial virus (RSV). Vaccine development will continue but certain steps can't be rushed.

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.

Are you referring to this study?

https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWS...

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.

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.

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.

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.

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.

It only needs to reduce the viral load significantly to become a better alternative to killing the economy with a lockdown.

> 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

This isn't very weird, is it? Most people didn't start to hear about COVID-19 until January this year and many others didn't start hearing about it until people got infected in their countries.

As with everything with clinical trials, even if it seems to be helping, it'll take many months before it'll be prescribed to people for treating COVID-19

Chloroquine (not AFAIK hydroxychloroquine) has been made available to doctors (and therefore patients) through "Compassionate Use."

This means that doctors can prescribe chloroquine to patients before and outside of a clinical trial. I suspect many will take the chance.

In effect, the US will be conducting a large-scale, semi-controlled clinical study on a drug with a significant side effect profile in the midst of the worst pandemic in 100 years.

> The President is doing something very dangerous

And if he didn't do what he did, you'd be saying the same thing once hundreds of people start dying per day because there's not enough chloroquine available. How do you know it's "hype"? Because orange man bad? It has shown effectiveness against SARS previously. It's been available for 50+ years and doctors are familiar with its side effects and safety profile. The Chinese list it in their official treatment guidelines right next to antivirals. It's also being used in France and Italy. Sure, the study produced in the last 2 weeks in France was not very rigorous, but it's not the only evidence of efficacy.

Could you quarantine your partisanship for a while? Maybe order it to shelter in place until, say, July?

I would say the same thing regardless of the man on the podium. You're the one bringing partisanship into this.

It's hype because nothing has been demonstrated yet using practices that have been worked out through a hundred years of painful trial and error. It's hype because he's saying he thinks it will work when he has no data to support that conclusion. It's hype because as the president must surely be aware, Americans are scared right now, and with good reason. To continue to double down on a "feel" in the current environment is hype.

The study from France, with its many flaws, is the only one that has been published. The "guidance" from the Chinese authorities is suspect to say the least.

> I would say the same thing regardless of the man on the podium.

Must have been hard for you to stomach 2009 then when 60 million Americans got infected with H1N1, nothing whatsoever was done, and the CDC budget was cut the very next year.

We didn't have to stomach much.

https://www.propublica.org/article/no-president-trump-the-co...

Didn't seem like it at the outset (which is where we are now) - the initial estimates were wildly inflated: https://academic.oup.com/eurpub/article/22/1/7/489927. And yet still, nothing whatsoever was done. Nobody was criticized for the lack of response, and, as I said above, the CDC budget was cut the following year.

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...

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

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.

> Those that have already been devastated by Fluoroquinolones are extremely upset to hear that a related quinolines drug is being proposed.

Raising awareness of the risks based on your personal experiences is reasonable. But the above statement seems to cross the line into irrationality by pre-deciding that quinolines aren't worth trying here. That casts doubt on whatever scientific arguments you put forth, because it doesn't seem like you're capable of being fair about this.

"Two drugs, chloroquine and remdesivir, are being designated for Expanded Access, or “compassionate use,” by the FDA."

It's already available. Hopefully soon to the general public (it's prescription only btw).

Sorry for your loss

As someone who is 2.5 years away from a fluoroquinolone reaction and still trying to get back they are no joke.

The mental/physical damage they can produce is not something you would expect.

I've been suffering badly from fluoroquinolone toxicity for 5 years. Doctors literally are clueless about it.

I had a bad reaction to Ciprofloxacin. These drugs are poison - they should be an absolute last resort.

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