Chloroquine phosphate has shown apparent efficacy in treating Covid-19
ncbi.nlm.nih.gov
ncbi.nlm.nih.gov
Highlights from that paper (all of which look quite reasonable to me, as a non-expert):
• In vitro data suggest that chloroquine inhibits SARS Cov-2 replication.
• In past research, chloroquine has shown in vitro activity against many different viruses, but no benefit in animal models.
• Chloroquine has been proposed several times for the treatment of acute viral diseases in humans without success.
• The outcomes of some current clinical trials of chloroquine in China have been announced, without access to the data.
• Peer review of the results and an independent assessment of the potential benefit for patients are essential.
This seems to be the link to the details of clinical trials in China that are made available
http://www.chictr.org.cn/searchproj.aspx?title=氯喹&officialna...
At the very bottom, it says "original data will be published on web-based public database in 6 months after the research" which is a bit disappointing.
People are incredibly prompt to jump in on unproven suggestions during a crisis, while at the same time shitting on standard evidence-based medical care all year long. Go figure...
A small-sized chinese study with unreleased data? Color me skeptical.
1. http://m.koreabiomed.com/news/articleView.html?idxno=7428
If you really knew the scientific state of clinical research, you would be far more skeptical.
Another interesting bit of data along those lines is the Chinese added chloroquine to their their treatment guidelines on feb 19th and their death rate dropped about 3 or 4x shortly after https://neutron-assets.s3-ap-southeast-2.amazonaws.com/img/c...
From experience, expert opinion situations are not too encouraging. But let's hope we're lucky this time.
Now if you'll excuse me, I'll be off intubating highly contagious cases without appropriate protection equipment if you're looking for me in the coming days. Personally, I'm hoping that the disease preferentially targets politicians and health ministers #-(
It seems to me beyond reasonable doubt that quinine derivatives are useful in humans. A miracle cure maybe not but almost certainly useful.
Keep in mind that antivirals only work well if you start taking the during the first two days, TCM is reasonably safe and over the counter, whereas if you're in the US then good luck even getting tested in the first 10 days let alone prescribed something.
C.f.: https://www.sciencedirect.com/science/article/pii/S104366182...
>The outcomes of some current clinical trials of chloroquine in China have been announced, without access to the data
Which are...?
"Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg chloroquine and 13% survival when treated with 1 mg/kg chloroquine. Our results show that chloroquine can be highly effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against HCoVs."
Shameless tangent, China has just booted its most competent respiratory disease epidemiologist from heading epidemic control committee for not backing Xi Jinping's "herbal remedies"
It’s up to you to choose which news source to believe, knowing that the former can print anything (including wild speculation) and the later will only print government approved information (including blatant obvious propaganda).
Not simply bad, but like a 180⁰ of the original meaning.
Well, there is rich context to this. Chinese mainland media has been for weeks escalating the "herbal remedies" craze, and Xi somehow managed to insert himself even there.
Now the media (propaganda ministry) can't back off, because Xi will look like an idiot if they are to back off and acknowledge how foolish it is.
For Zhong, a man with a known anti-quackery sentiment, not speaking in single voice with CPC's herbal remedy peddlers, was enough to be seen as somebody not standing in line.
Apparently not just weeks, but for a long time.
Imagine if homeopathy became a point of something the government says we have to see as cultural/national pride. And is prescribed by doctors/hospitals because of that, and scientific analysis has to show the results that also reflect that...
> TCM has never missed a single fight against epidemics throughout Chinese history. TCM classics have provided sufficient evidence of how TCM cured epidemic diseases such as smallpox over the past several thousand years.
I don't have any reason to trust an article from a Taiwanese publication over one from the PRC but the above quote leaves me highly sceptical about the rest of the article.
Not to downplay the issue here: there have been reports of doctors being forced to include herbal medicines in the treatment from higher up, despite having little evidence supporting their efficacy. Just a random fact check.
Sources (all in Chinese; note epochtimes doesn't have a particularly good reputation):
[1]: https://www.fmprc.gov.cn/web/fyrbt_673021/t1755063.shtml
Basically the goal is to allow zinc to get into a cell, it needs a helper to get inside the cell (a Zinc Ionophore). Apparently based on the 2nd video, Hydroxychloroquine is even more effective than Chloroquine. It's really important to note however that these are lab based findings, not from studies on patients.
Edit: https://www.macleans.ca/news/canada/a-made-in-canada-solutio...
Essential oils have been evaluated for their inhibitory activity against SARS-CoV and HSV-1 replication in vitro by visually scoring of the virus-induced cytopathogenic effect post-infection. Laurus nobilis oil exerted an interesting activity against SARS-CoV with an IC(50) value of 120 microg/ml and a selectivity index (SI) of 4.16. This oil was characterized by the presence of beta-ocimene, 1,8-cineole, alpha-pinene, and beta-pinene as the main constituents.
https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbdv.200890...
Thats the mechanism that works in test tubes, but not in humans so far. Pulling Zinc into cells is what determines this hypothetical effect, not to be confused with whatever has the strongest side effects.
Edit: just did a search and your insight led to this study on zinc and Coronavirus from 2010:
https://journals.plos.org/plospathogens/article?id=10.1371/j...
Abstract
Increasing the intracellular Zn2+ concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn2+ and PT at low concentrations (2 µM Zn2+ and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC). Using an activity assay for RTCs isolated from cells infected with SARS-CoV or EAV—thus eliminating the need for PT to transport Zn2+ across the plasma membrane—we show that Zn2+ efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli subsequently revealed that Zn2+ directly inhibited the in vitro activity of both nidovirus polymerases. More specifically, Zn2+ was found to block the initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp elongation was inhibited and template binding reduced. By chelating Zn2+ with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription.
Afraid that means I'll have to subtract 100 points from your tally and add a demerit for shoddy work during a crisis.
Mentioned:
Kaletra, an anti-HIV medication that includes the drugs lopinavir and ritonavir.
Hydroxychloroquine, sold under the brand name Plaquenil.
[1] https://www.upi.com/Top_News/World-News/2020/03/12/South-Kor...
https://twitter.com/katyw2004/status/1236848300143280128
verification tweet: https://twitter.com/mshah85/status/1237231277251514368
* It was used for centuries to combat malaria until it recently (~10yrs) became ineffective (I took some in the 80's for a year while working in Central America and had amazing dreams).
* It is the basis many awesome aperitifs: Byrrh, Bonal, [tonic water,] and other herbaceous spirits
If it can be used as an antiviral for COVID-19, well, that would be a really cool example of an old/ancient medicine still doin' its thing.
Here's google translate: "We organized more than a dozen hospitals in Beijing, Guangdong and Hunan provinces to jointly evaluate the safety and effectiveness of chloroquine phosphate in the treatment of new coronary pneumonia. In the clinic, we are very sure to see the curative effect, whether it is from the rate of exacerbation, antipyretic phenomenon or the image improvement time of the lungs, the negative time and negative rate of viral nucleic acid, and the shortening of the disease course, and a series of indicators, systematically Based on comprehensive research, the medication group was better than the control group. For example, a patient in Beijing was admitted to the hospital on the 4th day of the onset of disease at the age of 54. One week after taking the medicine, the nucleic acid turned negative, and all the indicators improved, meeting the criteria for release and isolation."
"Audio transcript of the news briefing held by the State Council of China on February 17, 2020. The National Health Commission of the People's Republic of China. http://www.nhc.gov.cn/xcs/yqfkdt/202002/f12a62d10c2a48c6895c... (accessed February 18, 2020). (in Chinese)"
Third reference in https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_202...
Yes chloroquine has been shown effective in vitro (https://www.nature.com/articles/s41422-020-0282-0). Yes hydroxichloroquine has been shown effective in vitro very recently as well (https://academic.oup.com/cid/advance-article/doi/10.1093/cid...).
Yes both compounds are already actively being used and approved for use by Asian and EU countries against Covid19:
Here are the Netherlands treatment guidelines (in Dutch): https://lci.rivm.nl/covid-19/bijlage/medicamenteuze-behandel...
Here are the Italy treatment guidelines (in Italian): http://www.simit.org/medias/1555-covid19-linee-guida-trattam...
How they found out about it: https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...
Approval and recommendation of the chinese: https://pubmed.ncbi.nlm.nih.gov/32075365-expert-consensus-on... https://pubmed.ncbi.nlm.nih.gov/32074550-breakthrough-chloro...
I don't think there is much doubt left about it's efficiency at this stage. Hydroxichloroquine is much safer than chloroquine and it's just a 5 day course at pretty low dosage (2x400mg on day1 as a charge dose, then 2x200mg for 4 days).
More importantly, the drug is readily available, mass producded and doesn't cost 300$+/box like lopinavir/ritonavir. This drug isn't also 100% experimental and probably in the 3 digits rangs like remdesivir.
The only real issue is that with a lot of doctors using it, the temporary shortage of the drug could be troublesome for many Lupus patients around the world who depend on Plaquenil for their management.
These trials and the validation can take about a year.
Here is the official list of currently being developed covid19 vaccines (all in pre-clinical stage)
https://www.who.int/blueprint/priority-diseases/key-action/n...
In the article I referenced, the company says they use a novel plant based method which allows mass production, and expect phase three clinical trials to be completed by November.
The company, Medicago, is not on the list you provided. It also seems to be a Pentagon funded biotech company so trying to understand how credible this news may be (I'm sure there are many unscrupulous companies trying to claim a miracle cure at this point!)
A reasonably opportunity to throw money at the problem would be to fund speculative production ramp-up for likely candidates ahead of approval, this should not be left to the invisible hand alone.
There are many variants of the flu. Most of them are well-enough understood to vaccinate against, and most of those have an already-tested-and-approved vaccine. The yearly flu vaccine is a combination of those vaccines for the strains the public health experts think are going to be an issue that season.
Sometimes they get it right. Sometimes they don't, and we have a bad flu season (see also: this year).
Here's a Planet Money rerun that talks about how they make the regular flu vaccine: https://www.npr.org/2020/03/06/812943907/episode-977-wheres-...
Transcript: https://www.npr.org/transcripts/812943907
However the Chinese seem prepared to cut corners on the testing and that:
"Coronavirus vaccine could be ready by April, Chinese officials say" https://nypost.com/2020/03/10/coronavirus-vaccine-could-be-r...
sorry if there is a smarter way to save comments
Report "Expert: Chloroquine Phosphate has a negative time of 4.4 days, faster than other drugs" (google translate) http://news.southcn.com/nfplus/gdjktt/content/2020-03/09/con...
I posted it on reddit (271 comments) https://www.reddit.com/r/COVID19/comments/ffztou/expert_chlo...
As an aside, the number of preppers and conspiracy theorists out on HN under stories like this is awful.
Remember, the world has vast infrastructures (CDC, WHO, NHS and equivalents) for working out the right course of action in these situations. They are staffed by professionals who understand how medicine and medical trials work, and how and when to deploy public health measures. I'm not saying their word is law, but hanging out on internet forums and then panic buying random stuff which isn't obviously efficacious off the back of a misunderstanding of the science is not personally or socially productive. At worst, it harms people in genuine need and stymies the ability of society to respond.
1) It's not random stuff; there is associated research and a theory of operation how it counteracts the virus
2) Lacking obviousness? By the time the research is settled, you may be very sick already.
3) There is no misunderstanding, there is a risk analysis based on the currently available knowledge. Risk of chloroquine poisoning X probability of effectiveness X risk of acute viral infection.
4) Crowd-sourcing information has shown to be very effective in other times of crisis, a viral outbreak is no different.
The internet is not a place for the information police. We share our ideas here.
G&Ts almost certainly won't have any effect on your susceptibility to infection nor your prognosis once infected. But they might help with (or make worse?) the anxiety associated with the panic.
And 6L of tonic water is... quite a lot.
Shudder.
The ibuprofen did its job though.
(I do not recommend this and am not a doctor)
Some enterprising Nigerian has apparently been trying to illegally sell it in the UK at least.
Also this would have a terrible effect and indeed cause supply shortages as another commenter pointed out.
There is some info here from a doctor https://www.reddit.com/r/medicine/comments/fbfj0r/covid19_pr...
There is some evidence that hydroxychloroquine may be better as a prophylactic. Here's medcram talking about it from in vitro results https://youtu.be/vE4_LsftNKM?t=192
Re real patients I thought this interesting on lupus patients using hydroxychloroquine at a hospital in Wuhan:
>In the early stage of the study group, through the clinical analysis of 178 patients with new coronavirus received by the hospital from December 2019, it was found that none of them was systemic lupus erythematosus. After that, in the consultation of 80 patients with systemic lupus erythematosus treated by dermatology department of the hospital, it was found that they were not infected with new coronavirus pneumonia. https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...
Which suggests it may work in real life. Lupus patient get a pretty high dose but looking at the in vitro stuff it looks like a low dose say 400mg/wk might work.
There may be a possibility here to save millions of lives - if this does go full pandemic with 60% global infection, taking say weekly hydroxychloroquine might reduce the effects to something mild flu rather than ICU death. It seems to me enough upside to make it worth doing a serious research effort which I don't think is being done.
I noticed when looking at the data, that while chloroquine facilitated a massive uptake a zinc, it was still true that increasing the extracellular zinc concentration (without chloroquine) still increased the cytosol's zinc concentration (by a lesser amount).
I promptly ordered zinc supplements. Obviously I'll see a doctor if I have symptoms, but I'll also hedge my bets.
i don't think anyone except hypochondriacs are in danger of zinc overdose
There is enough stupidity around in normal times, and now is worse.
Also a link to the study would be helpful.
however, I don't know about how it compares and if these are as potent as Chloroquine so it would be nice if an expert could opine on whether these natural compounds are as potent.
It's not fair to responsible people who are capable of researching safety and dosages to have to pay for the ignorance of others. Especially when this drug is OTC in most of the world. You don't need a medical degree to safely administer most drugs - and you should have the right to take that risk, even if that means ignorant people getting hurt or dying.
And I know I won't die because it's already safe enough to fight malaria. But maybe you don't know that. That's fine. I do. Let me arbitrage my knowledge.
Clinical trials are already fast-tracked during epidemics; if you're really interested you may even be selected for one. But going out and randomly buying medicine because it seems like it might work (even though it might not, but you're cured without it, which means you're going to go out and tell everyone else to go buy it too) might not necessarily be the best way to deal with this.
> But maybe you don't know that.
I am aware of chloroquine's use in malaria treatment.
Hey, that's okay, let me live or die on my own terms. It's my body. Stop trying to rule it.
I'm not making you take it. How about you don't make me not take it.
...but your body will take up a hospital bed and a team of healthcare professionals to deal with the side effects, thus taking them away from other patients.
The amount is negotiable to release you from your responsibility to me.
Nanny states breed incompetence.
Malaria prophylaxis is dosed -once- a weeek. Half-life 60-70 hours. Covid treatment is -twice daily-.
The therapeutic index of chloroquine in the treatment of covid-19 is relatively high. Some people take chloroquine or hydroxychloroquine at about half the acute dosage used for covid-19 (autoimmune disorders) for literal years.
Given the half life as you mentioned, once or twice a week with enough lead time would be a sufficient dosage against covid-19 too. It's just that if you want to reach the concentration of chloroquine that you would have to take it over a long time otherwise, you need very high doses. And since you're already infected and have a ton of the virus, you also need higher concentrations than for prophylaxis.
plaquenil on the other hand does have a higher therapeutic index.
The other major disadvantage is that these drugs can interact with protease inhibitors.
What are the possible consequences of this?
Kaletra, a protease inhibitor, is a combination of two drugs, one of which is a CYP3A4 inhibitor. It is used with some success on coronavirus patients.
Co-administering this with chloroquine 500mg/BID could easily result in chloroquine concentrations well above LD50.
At this point, I would label it as dangerous as aspirin.
As can inflating the price (high taxes) for non-doctors who are purchasing preemptively. If you are sick, go to a doctor and get it at the normal price. If you are a prepper, pay extra, buy less.
Looking at potential death puts gray market buyers in a weak negotiating position.
Basically instead of people choosing where it goes a government agency/hospital system chooses where it goes. After the CDC testing debacle, hopefully people understand that giving control to the government isn't a clear cut win. It is good if people have some control over their own destiny.
If you are relying on the hospital's goodwill and I'm willing to throw down $100k in bribes; I suspect I will mysteriously get myself an ICU bed. It would be better if that money went to the hospital where they can buy more beds than to corrupt administrators. Much like I can get toilet paper if I'm willing to pay $200 a roll; and it would be better if that was going to the manufacturer rather than drug dealers as is currently the case in Australia.
If I buy a test kit, mask, antiviral cocktail, ICU bed for myself, despite being unlikely to need it, and there's a shortage of these resources, I've lessened the sum effectiveness and response.
Personally? I assume the average person is an idiot, where nuanced topics that elicit emotional responses are concerned.
I'd choose experts doing their best to allocate effectively any day of the week.
The fact that experts are not perfect in no way bears on their nonetheless being better than the average person.
I find it darkly ironic that in the US their centralised control of the medical system has royally screwed up the ability of people to access test kits and that is likely to become a rallying point for people who want more centralised control of the medical system.
If you do buy those things then you can share them with your neighbors. Someone is bound to want that stuff - a few more community sponsored ICU beds, masks, test kits and antiviral cocktails would be just what most countries need.
Why?
You're comparing apples and oranges.
Perfect isn't a reasonable criteria. More effective than the average person is.
The options aren't "experts hold all the power" or "paniced hoarders have all the power". At the moment, the US has set the dial to experts holding all the power and badly flubbed the response; the obvious solution is a mix of expert- and non-expert- control so that when the experts inevitably muck up it isn't the end of the game.
If people want to allocate a massive % of societies resources to masks, ICU beds and COVID-19 tests they should be able to. At present, they aren't allowed to and the government doesn't seem to be reacting very quickly.
This is classic economics; centralised control and price control where vendors are scared of being dinged for 'price gouging' have immediately resulted in massive shortages. If the government encouraged prices to rise until supplies were only just running out and gave the medical system enough money to buy what they needed in that environment then the situation would resolve much more quickly.
The people making face masks, ventilators, ICU beds and similar should be rolling in so much money from panic buyers that it makes sense to hold emergency reserves for the next crisis. That isn't what is happening, so instead we won't have resources for this crisis or the next one. So called 'panic buying' leads to a very healthy economic response after a month or two; which is where we happen to be vs COVID-19. If we'd had more panic buying earlier we'd be in a better spot now, and rapidly moving to a better spot in a month or two. If we allowed people to allocate resources to testing and hospitals despite the opinions of centralised agencies we'd also be a better spot. People like Bill Gates can fight malaria but they can't fight the CDC.
> government doesn't seem to be reacting very quickly
> If the government encouraged prices to rise until supplies were only just running out and gave the medical system enough money to buy what they needed in that environment then the situation would resolve much more quickly
> So called 'panic buying' leads to a very healthy economic response after a month or two
Your argument would be stronger if you dropped the opinionated hyperbole.
If the government transferred funds through the market, vs direct purchases, then we'd be at the mercy of whatever the masses decided they wanted to buy.
As of a few days ago, this would have meant that millions of dollars went to toilet paper manufacturers.
You seem to be of the opinion that a free market knows best in crisis situations. I feel otherwise. Doubt I'm going to be able to change your mind.
Not actually true, hyperbole doesn't change the quality of the evidence or the strength of the argument.
> As of a few days ago, this would have meant that millions of dollars went to toilet paper manufacturers.
Nothing wrong with that. If people feel a desperate need to buy overpriced toilet paper then the toilet paper manufacturers and distributors should be encouraged to take advantage of that. If a roll cost $30 that would stop people buying trolleys of the stuff all at once. Instead, shops in Australia have held prices steady and run out of toilet paper; leaving me peeved I have to say. The situation is pretty much strictly worse than if the free market was encouraged in times of crisis.
> You seem to be of the opinion that a free market knows best in crisis situations.
No, not at all. But suppressing free market forces in a crisis is one of the worst possible responses because it delays the corrective action by suppliers. Prices should be shooting up and down, and governments should be giving hospitals emergency funding so they can buy what they need. That'll provide the best signals of what is needed in a crisis. I bet the free market understood the need for test kits a lot more than the CDC did in America; there would have been hospitals crying out to test people.