That's not the only possible mechanism of action. It is possible that it works by inhibiting endosome acidification.
Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases
I also have not identified any studies in the US that are using zinc with the HCQ. Maybe this is a mistake on their part, but you would think some smart people would have looked into this.
People … please at least try to understand what the non-technological Hail Mary play would be, that would unambiguously quash CV19 as a public menace.
[1] Slow disease's infection-rate — through a variety of barrier mechanisms. Distancing, masks, gloves; working-from-home, food take-out, delivery-to-home for goods via any of the stores' online agencies.
[2] Protect the vulnerable — We understand what sub-group these mostly are. Require persons living with such individuals use strong barrier methods or… total quarantining. Likewise, the vulnerable ought to be legally bound to protect themselves when out in public, as is necessary considering their locale, independence, living situation, all that.
[3] Quarantine the badly infected — whatever strain they have, needs additional attention to preferentially snuff out. Assuming “no science to determine strain” is available, then qualitative assessment and triage affords the most robust policy guidelines. Remember, China had NO robust testing, yet seemingly snuffed it.
[4] Invest in hopeful tech — sure, invest! Ventilators, high-effectiveness masks, disposables, consumables, all that. In a shooting war, both sides need a lot of catgut, scapels, bandages and antiseptic. In this war, masks, gloves, and so on.
[5] Set hard-nosed government policy — to effect the above. Fines. Fines-with-silver-linings: gloves and masks will be sent to you if you get and pay a fine for not having these in public.
Eventually № 5 will pay off. Vaccines, treatments, both. Much more well regarded procedurals for hospitals.
Some people will die. Most — the very most — will not. Everyone will either directly develop herd-immunity, or will gain a statistical advantage because of the conferred immunity afforded to the majority of the healthy public catching the bug.
________________________________________
In many regards, this is just taking from the playbook of the Great Spanish Flu, in terms of what science can, and likely can not do in the short term.
Still, we need firebreaks.
⋅-⋅-⋅ Just saying, ⋅-⋅-⋅
⋅-=≡ GoatGuy ✓ ≡=-⋅
[1] Slow disease's infection-rate — through a variety of barrier mechanisms. Distancing, masks, gloves; working-from-home, food take-out, delivery-to-home for goods via any of the stores' online agencies.
[2] Protect the vulnerable — We understand what sub-group these mostly are. Require persons living with such individuals use strong barrier methods or… total quarantining. Likewise, the vulnerable ought to be legally bound to protect themselves when out in public, as is necessary considering their locale, independence, living situation, all that.
[3] Quarantine the badly infected — whatever strain they have, needs additional attention to preferentially snuff out. Assuming “no science to determine strain” is available, then qualitative assessment and triage affords the most robust policy guidelines. Remember, China had NO robust testing, yet seemingly snuffed it.
[4] Invest in hopeful tech — sure, invest! Ventilators, high-effectiveness masks, disposables, consumables, all that. In a shooting war, both sides need a lot of catgut, scapels, bandages and antiseptic. In this war, masks, gloves, and so on.
[5] Set hard-nosed government policy — to effect the above. Fines. Fines-with-silver-linings: gloves and masks will be sent to you if you get and pay a fine for not having these in public.
Eventually № 5 will pay off. Vaccines, treatments, both. Much more well regarded procedurals for hospitals.
Some people will die. Most — the very most — will not. Everyone will either directly develop herd-immunity, or will gain a statistical advantage because of the conferred immunity afforded to the majority of the healthy public catching the bug.
________________________________________
In many regards, this is just taking from the playbook of the Great Spanish Flu, in terms of what science can, and likely can not do in the short term.
Still, we need firebreaks.
⋅-⋅-⋅ Just saying, ⋅-⋅-⋅
⋅-=≡ GoatGuy ✓ ≡=-⋅
The idea being that these measures will reduce the infection spread to less (hopefully way less) than 1:1.
dave
planet₁₀;6142177 said:
Yes, for some of us, they will. For others, not. The teens-to-early-adults group is particularly willing to 'cheat' on all the barrier protocols. A lot of cheating. I live with 6 of them on our property between 2 houses. Our “hard rules” or not, we've been finding them quietly cheating. No announcements, just visits to boyfriends' houses, and vice versa, that kind of thing.
Luckily, when (not if) they individually catch the bug, they're in the state-of-health-and-youth that is well regarded as being able to rebuff CV19's attack. This is why the Wife and I are taking an even harder-nosed approach at the in-house and inter-house barrier methods. Wearing masks (them and us) indoors, when in same rooms together. Continuously washing hands, surfaces, pots, handles, refrigerator doors, that kind of thing. Switches, bannisters, railing, … laundry, … and of course the now-ubiquitous Amazon bags delivered severalt times a day.
⋅-⋅-⋅ Just saying, ⋅-⋅-⋅
⋅-=≡ GoatGuy ✓ ≡=-⋅
How many more patients should be studied to be considered as data?
Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients
^ I should be more careful in what I say, apologies.
This serves to add to the body of some efficacy, which is why the treatment is being recommended for worst-case patients. That data is still coming, but widespread hasn't shown to be a smoking gun. I hope to be wrong as the data comes out, but we have to work with what we have.
And the zinc-hydroxychloroquine relationship/mechanism, which was cited previously, hasn't had legs so far. Just hydroxychlorquine.
This serves to add to the body of some efficacy, which is why the treatment is being recommended for worst-case patients. That data is still coming, but widespread hasn't shown to be a smoking gun. I hope to be wrong as the data comes out, but we have to work with what we have.
And the zinc-hydroxychloroquine relationship/mechanism, which was cited previously, hasn't had legs so far. Just hydroxychlorquine.
I am eager to see results out of NY and I believe somewhere in the midwest where they are doing a trial of HCQ as post-exposure prophylaxis.
There is enough evidence to convince me that hydroxycholorquine is at least somewhat effective in reducing viral load - however, giving the drug to patients that are already hospitalized might be setting it up for failure. Daniel Griffin, an ID doc in NY mentioned on that podcast I liked in the first post that they have observed their patients can develop ARDS despite decreasing viral load, suggesting immune response is problematic. As a layperson, it seems that hydroxycholorquine would be best used on symptomatic patients before they develop significant disease.
I have observed how this disease has progressed over the last few weeks with my primary reference being the Johns Hopkins Dashboard.
Operations Dashboard for ArcGIS
So confirmed cases worldwide are currently running at 0.8million which of course in terms of world population is minuscule amounts. We can only assume that the confirmed cases are mostly the very sick. For instance in the UK there are 25474 confirmed cases with approx 9000 in hospital and 1793 dead. (31 March 20) Hopefully the actual number of cases exceeds this by a large amount of the population, that are starting the process of herd immunity.
The process of social isolation is slowing down the spread of the infection which is helping our health services cope. Where that capacity is exceeded then many more die as is seen in Italy where over 10% of reported cases have been fatal. Overall global fatality of Reported cases is 4.9%
We have seen in China & Korea that the rate of infection can be controlled to manageable levels. The critical stage now being what happens in these countries as the social distancing is relaxed.
The Imperial College report from March 16th
https://www.imperial.ac.uk/media/im...-College-COVID19-NPI-modelling-16-03-2020.pdf
Projects that social distancing measures will need to be repeatedly implemented over the next few years.
The infection will keep on spreading as we do not have a cure. If the estimates are correct maybe 60% of the world population could become infected. By slowing down the rate of infection we are helping to give those who become seriously ill more chance of survival.
Operations Dashboard for ArcGIS
So confirmed cases worldwide are currently running at 0.8million which of course in terms of world population is minuscule amounts. We can only assume that the confirmed cases are mostly the very sick. For instance in the UK there are 25474 confirmed cases with approx 9000 in hospital and 1793 dead. (31 March 20) Hopefully the actual number of cases exceeds this by a large amount of the population, that are starting the process of herd immunity.
The process of social isolation is slowing down the spread of the infection which is helping our health services cope. Where that capacity is exceeded then many more die as is seen in Italy where over 10% of reported cases have been fatal. Overall global fatality of Reported cases is 4.9%
We have seen in China & Korea that the rate of infection can be controlled to manageable levels. The critical stage now being what happens in these countries as the social distancing is relaxed.
The Imperial College report from March 16th
https://www.imperial.ac.uk/media/im...-College-COVID19-NPI-modelling-16-03-2020.pdf
Projects that social distancing measures will need to be repeatedly implemented over the next few years.
The infection will keep on spreading as we do not have a cure. If the estimates are correct maybe 60% of the world population could become infected. By slowing down the rate of infection we are helping to give those who become seriously ill more chance of survival.
Attachments
From what I gathered extra zinc is not necessary, the trick is to get the zinc into the cells which is seemingly what hydroxychloroquine and quercetin do by opening up pathways. It is the zinc which reduces or even stops the virus from replicating and too much zinc is not good either.
The important thing is NOT to be zinc deficient.
What I do is just that for the time being I take a one-a-day vitamin and mineral supplement which provides the rec. daily doses but is not strong enough to provide too much.
And we won't because there is no time to do the required double blind test with control groups which is needed to produce actual data.
We might get acceptable data some time after this whole thing is over but that would be too late for many.
Meanwhile I did show that video to my daughter and she thought it all makes perfect sense.
She has got a Masters degree in Pharmacology.
That is the paper with some quite unrealistic input variables that has probably led to some 10x as many cases than if things had locked down (a loose term given the pictures of brits getting off the train). You can always use about a 10x as a multiplier of the confirmed cases to guess the actual number. This number has a significant spreaddepending on how heavily testing is done, how soon lockdown occurred and how deep into the crisis each country is in.
If we take a look at some of the numbers (they will change daily), S Korea has tested about 4%, Iceland 3%, Canada 0.62%, the US greatly expanding testing is up to about 0.3% most i expect in heavily hit states, but the real need is in the states not widely hit, so that a handle can be gotten on the situation. Knowing what is actually happening would be very useful, but we are not there yet.
Estimates are that the USA should have acted a month earlier… with the 40% per day multiplier that is 42 times as many cases.
dave
It won't be perfect, but I think we will have enough data in a month or two to at least estimate if it's helping outcomes.
I'm sure you already know that just because something works in vitro and the mechanism of action makes complete sense does not mean it can actually influence the disease outcome.
I'm hopeful that it will be at least mildly effective. Since it's an oral tablet, if it is effective then it would ideally be administered as early as possible in the course of the disease. The problem with Remdesivir, other than availability, is that it's not orally bioavailable and requires infusion. Impossible to start early in the course of the disease where antivirals are best suited.
We do know that South Korea has used hydroxychloroquine extensively and I know that it was in short supply in Germany last week so I assume they are using a lot of it and there is no malaria there to the best of my knowledge.
Meanwhile the last two updates of MedCram are quite interesting touching on how hydrothermal therapy may be useful to activate our innate immune system. Something we are able to do at home and it may lead to a reduction in hospitalization due to pneumonia. It doesn't cost anything and does no harm.
Meanwhile the last two updates of MedCram are quite interesting touching on how hydrothermal therapy may be useful to activate our innate immune system. Something we are able to do at home and it may lead to a reduction in hospitalization due to pneumonia. It doesn't cost anything and does no harm.
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The guy giving these numbers was a prof from one of the research universities. For normal flu, for example, you need to be exposed to it for days. With Coronavirus if someone sneezes on you, you’ve probably got it.
Mortality rate 0.1% vs 3%
I agree, these are sensational numbers.
Then there’s Ebola- also highly contagious but with a mortality rate of 50%.
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Hell is Coming: Here is the Mathematical Proof
Sensational title but the math seems to work.
On a positive note I heard that the rate of new infections is slowing down.
Sensational title but the math seems to work.
On a positive note I heard that the rate of new infections is slowing down.
I'd appreciate if you did follow through and quote the response I made to Indra, which did clarify things more, including exactly what you wrote. There is tremendous interest in reappropriating approved drugs for COVID-19, including a few oncology drugs (we are looking at the TMPRSS pathway, which is critical for a second cleavage of a domain before the virus can enter; Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers in COVID-19 - CEBM)
Lots of things make intuitive sense medicine-wise that end up absolutely nowhere. And by that I mean 95% of it. (Or manages to be so toxic that whatever you're trying to treat is less harmful than the drug)
So I'll admit, based on the abstract that the whole zinc uptake thing, I didn't realize folks were using that as basis for how hydroxychloroquine was potentially helpful.
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The marseille study got a lot of critic due to some methdological flaws that might have had an impact. Small sample sizes in such experiments tend to overemphasize any positive effect (if existent at all), but it nevertheless seems to be worth to try.
Ioannidis has a new paper out, mainly pointing to the negative effects of exaggerations and uninformed decisions due to missing data:
Error - Cookies Turned Off
There is an interview on youtube where he explains his concerns:
YouTube
Basic line among most experts I've read about or listen to seems to be that the measures taken so far should (most likely) be taken because the alternative of doing nothing and hope does not seem reasonable.
Some countries choose this option (at least for some time) and among others there are some differences in the measures taken and only the next couple of weeks will show (after adjusting for confounders) if there are differences in the outcomes.
There is a lot still not known about it - range of mortality is now 0.05% - 1%, Rob is now 1.3 - 2.5 (presumably unfortunately only in this range for developed countries with high quality health care) - as Ioannidis pointed out, there is often no real evidence available to support decisions for various measures.
So it seems to be crucial to get better data, Lakens proposed a different test strategy to get an overview about the already existent spread among the countries and to identify possibe hot spots, but that needs constant repetition on randomized groups and I assume will work best, if the antibody tests are available and working with high sensitivity and specitivity.
On a personal level, it seems that more and more experts are agree on the benefits of wearing masks. Mufflers and alikes will help also.
It seems that the diy-community is already spreading a lot of ideas for masks, shields and so on.
Reducing the virus load seems always a good idea as DPH mentioned; Charles Darwin's tip with the zinc needed is a good one, usually the supplements come already in combination with supporting transport ingredients.
John Campbell cited the meta-analysis for the benefits of supplemental vitamin D (regular daily dose seems to work better than high dose shots) but it seems that some addition like vitamin K and magnesium might be needed to get the best from the vitamin D. The meta-analysis only examined the vitamin D without any further supplements.
Vitamin C helps usually too, but if taken in high doses seems to inhibit the absorbtion of zinc.
Obviously it would be best to eat a daily food mix that already contains everything we need in best doses but it is IMO very unlikely that those of us who are not farming in a green paradise will be able to get it.
Working with supplements needs some care to avoid mutual countereffects.
Ioannidis has a new paper out, mainly pointing to the negative effects of exaggerations and uninformed decisions due to missing data:
Error - Cookies Turned Off
There is an interview on youtube where he explains his concerns:
YouTube
Basic line among most experts I've read about or listen to seems to be that the measures taken so far should (most likely) be taken because the alternative of doing nothing and hope does not seem reasonable.
Some countries choose this option (at least for some time) and among others there are some differences in the measures taken and only the next couple of weeks will show (after adjusting for confounders) if there are differences in the outcomes.
There is a lot still not known about it - range of mortality is now 0.05% - 1%, Rob is now 1.3 - 2.5 (presumably unfortunately only in this range for developed countries with high quality health care) - as Ioannidis pointed out, there is often no real evidence available to support decisions for various measures.
So it seems to be crucial to get better data, Lakens proposed a different test strategy to get an overview about the already existent spread among the countries and to identify possibe hot spots, but that needs constant repetition on randomized groups and I assume will work best, if the antibody tests are available and working with high sensitivity and specitivity.
On a personal level, it seems that more and more experts are agree on the benefits of wearing masks. Mufflers and alikes will help also.
It seems that the diy-community is already spreading a lot of ideas for masks, shields and so on.
Reducing the virus load seems always a good idea as DPH mentioned; Charles Darwin's tip with the zinc needed is a good one, usually the supplements come already in combination with supporting transport ingredients.
John Campbell cited the meta-analysis for the benefits of supplemental vitamin D (regular daily dose seems to work better than high dose shots) but it seems that some addition like vitamin K and magnesium might be needed to get the best from the vitamin D. The meta-analysis only examined the vitamin D without any further supplements.
Vitamin C helps usually too, but if taken in high doses seems to inhibit the absorbtion of zinc.
Obviously it would be best to eat a daily food mix that already contains everything we need in best doses but it is IMO very unlikely that those of us who are not farming in a green paradise will be able to get it.
Working with supplements needs some care to avoid mutual countereffects.
It has an incredibly "velcro-ey" outer surface (That's a technical term. 🙂) so it sticks to everything pretty tenaciously and has a pretty long half life on most materials.
R0, which is the boots on the ground infection rate, wouldn't fall from that number, so I wonder if he's speaking to the above.
Perhas in the hard hit states where it is worst. I fear for what will happen when it hits the other states. I fully expect that US won’t peak for months — unless we get a silver bullet — could be as simple as one of the new fast tests (saw one that suggest 2 min), if they work and if they can churn enuff of them out soone enuff.
dave
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