Quote from Dr Richard

OK then what about all the travellers who've regularly used quinine analogues visiting malaria infested regions? Were any major qualms raised then when these drugs were used against malaria? No. Yes they do have side effects like cardiac arrhythmias and ECGs can be monitored so those with dodgy tickers could be advised to take favilavir or another antiviral like remdesavir if availiable. Or use lower doses. To achieve micromolar concentrations intracellular only 50 - 100 mg hydroxychloroquine daily would be necessary over a period of a week or so, together with 30 mg Zn citrate as supplement in case of Zn deficiency. I have contacted the BBC about this under their Q and answer session and hope to ask their reporters why the NHS and government are doing precisely nothing about anti viral treatment here in the face of good evidence that it has been highly effective elsewhere (China, S Korea, Japan). Let's see if it is effective in Italy now it has at long last been approved there. Nothing to stop Amazon distributing it on humanitarian grounds.

The issue is whether the anti-malarial doses are as high as the necessary anti-viral doses.

Malarial prophylactic dose:

Usual Adult Dose for Malaria Prophylaxis

Suppression: 400 mg (310 mg base) orally on the same day every week

From : https://www.drugs.com/dosage/h…e_for_Malaria_Prophylaxis

That is 60mg per day

For malarial treatment it is 400mg or 800mg per day.

Anti-viral dose used in trial:

All patients in Marseille center were proposed oral
hydroxychloroquine sulfate 200 mg, three times per day during ten day

That is 600mg per day.

See the difference? This is a drug which has known side effects on heart. Malaria also has known effects (it kills) so you balance that when treating the disease.

Not that we should not use it, just that risk/benefit needs to be considered at the 10X higher dosage.

You suggest it may be protective (or something) at much lower dosages. I'm not sure on what evidence? But I'm all for more trials to find out! I agree, at lower doses it is pretty safe (though even so not completely).

Two hopeful developments:

Experts at a hospital have developed some way to stretch supplies. They are taking mask intended for one-time use and sterilizing them with methods that do not damage the masks, with UV light. They determined the masks are as good as new. This technique can avert shortages.

https://www.nytimes.com/2020/0…onavirus-masks-reuse.html

Someone here reported that ventilators can be modified to be used by 2 patients. I read that it might be possible to use one machine with 4 patients. I think this may be sub-optimal. It would better to use the machine with only one patient. But if this can save 3 more people of course it should be done.

I think you are being overly picky here for Christ's sake this is not analysing calorimeter spreadsheets for signs of fiddling the datal Oh yes, Prof Didier Raoult only treated those patients he thought would recover anyway? Is there no respect for expert medical professionals anymore?

Quote from Dr Richard

I think you are being overly picky here for Christ's sake this is not analysing calorimeter spreadsheets for signs of fiddling the datal Oh yes, Prof Didier Raoult only treated those patients he thought would recover anyway? Is there no respect for expert medical professionals anymore?

That is not what I said. But yes, because he is a doctor, he would make sure that only those patients who would be most likely to benefit from the trial went on it, e.g. none with heart co-morbidities.

Quote from JedRothwell

This is VERY IMPORTANT:

A plea from NYC physicians: Our window of opportunity is closing to avoid Italy's fate

https://thehill.com/opinion/he…unity-is-closing-to-avoid

From the above (alas all too true):

This pandemic lays bare a simple truth: We’ve built a world that is greatly focused on the nonessential, but also a world where we lack many truly essential things.

It appears here that Trump is really pushing this cocktail today - see below. It’s hard to know if he is doing this because he is being fed private data on it that we all don’t know about, or he is simply seeing the same public reports we are.

The thing to keep in mind is that any drug cocktail that is shown to be effective is still 6-8 weeks from widespread use. I don’t see the experimental phase being able to move any faster than that. There needs to be a clinical trial phase with good data and published results. Compassionate use and Approved use are two different things, as they should be.

Put me in the camp that there is a decent possibility that we will have some kind of antiviral drug cocktail in the next 8 weeks that is shown to be somewhat beneficial. But it’s also good not to have too much false hope. Nothing is guaranteed at the moment. And it’s still a month or two where testing and isolation are the action steps to take.

https://www.mediaite.com/news/…-the-history-of-medicine/

The evidence for quinine analogs having prophylactic activity with 400 mg weekly doses is that it was accurately reported early on in the epidemic the surprising observation that no African nationals working in China who were exposed to COVID19 in Wuhan area became ill. Secondly all sub-Saharan malarial regions have only one or two reported cases to date (check the Worldometer). Barring S Africa which is no longer ridden with malaria so anti-malaria drugs are no longer widely used there. As you say a 400 mg weekly dose is sufficient for malaria prophylaxis because of the very long half life of hydroxy-metabolites concentrated intracellular by lysosomes and other organelles. Didier Raoult may have used unnecessarily high doses to make sure he obtained a clear result at 600 mg per day as clinicians are prone to do. I think only 50-100 mg hydroxchloroquine would be required to maintain prophylaxis or inhibition of viral spread and replication in tissues at the 1 micromolar therapeutic level (reported EC50 0.37 uM). MORE STUDIES ARE NEEDED TO CONFIRM any of this.

Quote from Deleo

It appears here that Trump is really pushing this cocktail today. It’s hard to know if he is doing this because he is being fed private data about it that we all don’t know about, or he is simply seeing the same public reports we dol.

The thing to keep in mind is that any drug cocktail that is shown to be effective is still 6-8 weeks from widespread use. I don’t see the experimental phase being able to move any faster than that. And there needs to be an clinical trial phase with good data and published results. Compassionate use and Approved use are two different things, as they should be.

https://www.mediaite.com/news/…-the-history-of-medicine/

(1) Trump does not understand science, nor believe scientists

(2) he does not have a nuanced approach to anything

it was accurately reported early on in the epidemic the surprising observation that no African nationals working in China who were exposed to COVID19 in Wuhan area became ill. Secondly all sub-Saharan malarial regions have only one or two reported cases to date (check the Worldometer)

So in both cases:

(1) we'd need to know numbers ill early in the epidemic and number of African nationals. This type of anecdotal info is awfully easy to inflate. If the reports have enough context I'd be interested, Please link them.

(2)

(a) The age profile there (posted ages ago) means the expected serious case rate is lower by a factor of 10

(b) The effect of strong sunlight on the virus is to destroy it, we are not sure how strong this "Summer" effect is on transmission

(c) Again if people spend more time outside, have better ventilation in buildings which are warmer, we don't know how this affects rates

(d) The number of exposed people in these regions is much lower, so not surprising if it is just starting there.

(e) Worldometer only reports tested confirmed cases. How many tests are they doing? Do you know?

If you see this as strong evidence then i'm sorry - i don't see how it can be that.

The Doctor Who Helped Defeat Smallpox Explains What's Coming

https://www.wired.com/story/co…-smallpox-epidemiologist/

Quote from Shane D.

IMO, the critics, and in particular the media, have done a great disservice in this time of crisis by integrating politics, into their duty to keep the public informed of the facts. For the average person, they do not know where the reporting ends, and the politics, personal agendas, begin.

Now if we could all please be more careful in keeping politics out of it. Yes, it is hard, and some will slip in no matter, but we have been doing a good job of it so far, so no reason we can't keep on being good little boys and girls.

Shane: we need to consider which political leaders do believe scientists when analysing this? Trump (AGW) does not. Nor do a few others. BJ in the UK on the other hand does believe scientists. In neither case is the statement coloured by my political views.

Neither Trump nor BJ understands science: they do not have the background to do this having been immersed in real estate dealing or (non-Science) journalism. In fact few political leaders do understand science. It is not a requirement, providing they can correctly weight the statements of scientists.

Those are not political statements, just facts that we should consider when weighing what different leaders say.

THH

There are lots of silly reports about the Chinese doctors thinking that one Cameroon man survived the corona virus because of his genetic makeup. And another a young Egyptian. I was wrong about this & cannot find any other evidence reported in respectable media, it was unfortunately just anecdotal the evidence linking taking quinine related antimalarials giving protection against coronavirus. Doesn't mean that the idea is wrong or shouldn't be investigated further though. Apologies.

Quote

The issue is whether the anti-malarial doses are as high as the necessary anti-viral doses.

Uhho! Extreme caution here. Chloroquine and hydroxychloroquine have 1) low therapeutic margin (therapeutic dose is close to toxic dose, at least in some people) and 2) a nasty toxicity profile with deaths reported with no more than 3x the therapeutic dose. The drugs are absolutely contraindicated in heart patients with a prolonged Q-T interval on their EKG. Unless you are young and healthy, you would ideally need a checkup and EKG before using chloroquine or derivatives. To make things worse, having given chloroquine, you can not withdraw it. It has a viciously long half life in blood and tissues and even dialysis will not remove it. There is no antidote. Nature has not been kind. Nature is a mother ... fu**er!

I have some family who are in their 60's and have congestive heart failure or other heart disease. They are especially at risk for COVID-19. But they are also wildly at risk for chloroquine adverse effects, including cardiac arrhythmias which can be quickly lethal. Should they be infected, it would be a very difficult decision to treat them with chloroquine. I have thought about this a lot. I would leave the final decision to them and their cardiologist but would suggest starting 200 mg only (per day) of hydroxychloroquine and normal doses of azythromycin (which also rarely has cardiac toxicity). This would require a positive COVID-19 RT-PCR test or highly suggestive, worsening symptoms including a fever and cough. I hope I never face that dilemma but I am afraid I and many others will.

ETA: to THHuxleynew : for people with known healthy hearts, a one week or ten day course of hydroxychloroquine 200 mg three times a day should be a lot safer than having untreated symptomatic COVID-19 infection. Plus it reduces viral shedding *if* and it's a big if, the Raoult et. al. study out of Marseilles is correct.

But thinking only scientists opinions are the way out of this, is incorrect.

Agreed. And I've never said scientists should lead, or make these difficult decisions.

I will continue to think that ignoring the views of scientists is both foolhardy and silly. And for non-scientists to put their hunches about science, above opinions of scientists, is stupid.

You will find for example on this issue that scientists have a range of views about what should be done, but that nearly all will say the Marseille trial results are very interesting, and need urgent follow-up, but are no way conclusive. They could just be a false dawn. Whetehr you'd want to try that treatment on patients before further tests would depend on doctor and patient I guess, and specifically on how serious a case it is and whether the patient has any contra-indications for chloroquinine.

Given that a politician could make various decisions, and say, for political reasons, various things. But Trump has stated many times that he does not believe even very strong consensus scientific opinions. That makes his statements of less value. You'd not expect what he says to be more accurate due to undisclosed high level scientific information he holds, as has been suggested here might be true.

I have some family who are in their 60's and have congestive heart failure or other heart disease. They are especially at risk for COVID-19. But they are also wildly at risk for chloroquine adverse effects, including cardiac arrhythmias which can be quickly lethal. Should they be infected, it would be a very difficult decision to treat them with chloroquine. I have thought about this a lot.

Yes, I agree. That was the point of my point about cardiac co-morbidities - alas we know that the same risk factors for Chloroquine and derivatives are also risk factors for COVID, which makes use of this drug, if it is useful, more problematic. However, nonme of those things mean that it might nnot perhaps be helpful overall: just we do not yet know and the evidence for is still weak, though interesting.

It is black and white thinking - ignoring the existence of trade-offs - that sounds good but is medically and scientifically bad.

Quote from Alan Smith

The French SANOFI laboratory has offered 1 million doses of PLAQUENIL (chloroquine) for treating 300,000 patients contaminated with Covid19..

That's what you call a clinical trial.

No!

But I'm sure in addition to that there will be some hard data generated with randomised participants.