The Association of American Physicians & Surgeons (AAPS) Urges President and
First Lady to Protect Nation with Early Treatment for COVID-19
Covers 100% what we have told the last 6 months. It's a pitty that doctors did need 6 months to understand it not even to talk about 200'000 dead Americans...
This says that Wilson was "never the same" after recovering from the flu. I have read that about several other people. They recovered, but they were weak, and seemed much older. The same may be true of COVID-19.
Flu, AFAIK, develops into pneumonia and consequent possible scarring of lung tissue.
COVID does that too - but it has an extra effect that certainly Flu does not so easily replicate, which is that blood vessels everywhere start leaking and blood clotting and this shows in long-term heart, kidney, brain problems as well as typical lung scarring.
Since these problems are caused by a cytokine storm (bradykinin induced most likely) that is directly induced locally by virus proteins, rather being just the bodies normal immune response, things are a lot worse typically than Flu in terms of long-term aftereffects.
That much is known, though the exact mechanism is still under investigation - similarly how to stop it.
For example (comment on the link above):
This is my first post here but I have to say that I’m struggling that anyone is taking bradykinin seriously. The amount of ACE2 in the lungs is negligible. Anyone can go to the human protein atlas to see for themselves the tissues where ACE2 is strongly expressed.
https://www.proteinatlas.org/ENSG00000130234-ACE2/tissue
And read the following publications
https://pubmed.ncbi.nlm.nih.gov/32715618/
https://pubmed.ncbi.nlm.nih.gov/32675206/
https://pubmed.ncbi.nlm.nih.gov/32170560/
And compare and contrast these 2020 publications to the 2004 publication which shows abundant ACE2 in lungs
https://pubmed.ncbi.nlm.nih.gov/15141377/
And then go to this Nottingham COVID Research Group website to see that ACE2 does NOT get up-regulated in severely ill patients
https://www.nottinghamcrg.info/results
To recap, ACE2 is not responsible for severe COVID-19 lung disease. It cannot be because there is not enough of it to sustain a serious infection in that organ.
Whereas Neuropilin-1, which is abundant in the lungs, has been shown to be a SARS-CoV-2 receptor
https://www.biorxiv.org/content/10.1101/2020.07.29.227462v1
We (https://arxiv.org/abs/2004.10274) and others (PMID:32130973) think that integrins will join Neuropilin-1 as receptors in the lungs. The best evidence so far to be made publicly available for the role of integrins as SARS-CoV-2 receptors can be found on the Nottingham website linked above.
Taming the cytokine storm: repurposing montelukast for the attenuation and
prophylaxis of severe COVID-19 symptoms (montelukast = Singulair)
On that topic, it is welcome people are thinking about that like this paper proposing montelukast. The real progress treating COVID will come from inhibiting that storm and all of the consequent short and long term problems. Once we have done that COVID really does become something like Flu, very nasty, and will kill some, but no worse than many other things.
The trouble is that the cytokine (or bradykinin, or hyaleurin) storm is incredibly complex (as you can see from the above argument with the bradykinin hypothesis) and while we know all these things correlate we don't really know cause and effect well, and hence don't know which interventions, blocking or promoting a particular interaction, will work. Most likely we already have drugs that in a suitable cocktail, carefully dosed, will be remarkably effective. Finding them is the problem because in vitro experiments and simulations can't study the whole system, and trials on people don't give you much information each trial so it can take a long time to work out all the candidate helpful drugs and then how they combine.
I guess we can hope eventually we get a really good understanding of all the cytokine system interactions and then work out theoretically what would be a good bet. It will be a big deal for medicine understanding this, and we are in a much better place to do this now than we were even 10 years ago.
Coming back to montelukast. The theoretical justification for that does not mention bradykinin, nor these other new ideas that studying COVID has provoked, and therefore is a bit incomplete. Does not mean it is wrong, just all these "it might work" justifications are uncertain, only a few will actually pan out.
THH
On the subject of monoclonal antibodies as treatment - since this is topical - obviously anything that reduced viral replication will reduce the cytokine storm effects. I guess the question is how well this works - normal wisdom is that anti-virals - including monoclonal antibodies, and not that much help once the infection has taken hold. COVID might be different not least because a high viral presence in the body seems associated with all this cytokine storm nastiness.
They do not always wear masks. They sometimes did in the past. Now they all have masks. In the past, you might see one or two people in a train car wearing masks, mainly for their own comfort, as I explained above. Now, everyone wears one. I am sure there is a tremendous difference in the infection rate for colds and influenza between the situation where one or two people wear masks, and everyone wears one. Previous years are not comparable.
I spent a few weeks in Japan last year. About 30% of people on subway trains wore masks. On city streets, about 15%. On intercity trains and rural buses, and in rural towns and villages, very few. In restaurants and shops, virtually none. On the hiking trails, none at all.
So far as I was aware, I caught no viruses; despite taking many subway journeys at busy times when whatever the opposite is of social distancing (?social cramming?) is practiced
Display MoreFlu, AFAIK, develops into pneumonia and consequent possible scarring of lung tissue.
COVID does that too - but it has an extra effect that certainly Flu does not so easily replicate, which is that blood vessels everywhere start leaking and blood clotting and this shows in long-term heart, kidney, brain problems as well as typical lung scarring.
Since these problems are caused by a cytokine storm (bradykinin induced most likely) that is directly induced locally by virus proteins, rather being just the bodies normal immune response, things are a lot worse typically than Flu in terms of long-term aftereffects.
That much is known, though the exact mechanism is still under investigation - similarly how to stop it.
For example (comment on the link above):
This is my first post here but I have to say that I’m struggling that anyone is taking bradykinin seriously. The amount of ACE2 in the lungs is negligible. Anyone can go to the human protein atlas to see for themselves the tissues where ACE2 is strongly expressed.
https://www.proteinatlas.org/ENSG00000130234-ACE2/tissue
And read the following publications
https://pubmed.ncbi.nlm.nih.gov/32715618/
https://pubmed.ncbi.nlm.nih.gov/32675206/
https://pubmed.ncbi.nlm.nih.gov/32170560/
And compare and contrast these 2020 publications to the 2004 publication which shows abundant ACE2 in lungs
https://pubmed.ncbi.nlm.nih.gov/15141377/
And then go to this Nottingham COVID Research Group website to see that ACE2 does NOT get up-regulated in severely ill patients
https://www.nottinghamcrg.info/results
To recap, ACE2 is not responsible for severe COVID-19 lung disease. It cannot be because there is not enough of it to sustain a serious infection in that organ.
Whereas Neuropilin-1, which is abundant in the lungs, has been shown to be a SARS-CoV-2 receptor
https://www.biorxiv.org/content/10.1101/2020.07.29.227462v1
We (https://arxiv.org/abs/2004.10274) and others (PMID:32130973) think that integrins will join Neuropilin-1 as receptors in the lungs. The best evidence so far to be made publicly available for the role of integrins as SARS-CoV-2 receptors can be found on the Nottingham website linked above.
On that topic, it is welcome people are thinking about that like this paper proposing montelukast. The real progress treating COVID will come from inhibiting that storm and all of the consequent short and long term problems. Once we have done that COVID really does become something like Flu, very nasty, and will kill some, but no worse than many other things.
The trouble is that the cytokine (or bradykinin, or hyaleurin) storm is incredibly complex (as you can see from the above argument with the bradykinin hypothesis) and while we know all these things correlate we don't really know cause and effect well, and hence don't know which interventions, blocking or promoting a particular interaction, will work. Most likely we already have drugs that in a suitable cocktail, carefully dosed, will be remarkably effective. Finding them is the problem because in vitro experiments and simulations can't study the whole system, and trials on people don't give you much information each trial so it can take a long time to work out all the candidate helpful drugs and then how they combine.
I guess we can hope eventually we get a really good understanding of all the cytokine system interactions and then work out theoretically what would be a good bet. It will be a big deal for medicine understanding this, and we are in a much better place to do this now than we were even 10 years ago.
Coming back to montelukast. The theoretical justification for that does not mention bradykinin, nor these other new ideas that studying COVID has provoked, and therefore is a bit incomplete. Does not mean it is wrong, just all these "it might work" justifications are uncertain, only a few will actually pan out.
THH
On the subject of monoclonal antibodies as treatment - since this is topical - obviously anything that reduced viral replication will reduce the cytokine storm effects. I guess the question is how well this works - normal wisdom is that anti-virals - including monoclonal antibodies, and not that much help once the infection has taken hold. COVID might be different not least because a high viral presence in the body seems associated with all this cytokine storm nastiness.
TH,
How can “blood vessels leak and clot at the same time”?
How can “blood vessels leak and clot at the same time”?
It's what happens when you cut yourself. Blood comes out and the clotting mechanism tries to prevent it. The two things are (in part at least) sequential rather than simultaneous.
How can “blood vessels leak and clot at the same time”?
The leaking is caused by the "bradykinin storm" as all blood vessel contain ACE2 receptors. The clothing is a direct effect of the virus as it strongly binds the iron of hemoglobin and is also able to remove it. Some believe that the iron does poison the tissue and not the "bradykinin storm". But we have to wait some more months/years to understand this new disease.
Avigan (See Japan https://www.japantimes.co.jp/n…-coronavirus-drug-avigan/) in general has shown the same power as remdesivir as a general treatment and certainly will be 100x cheaper!
Swiss update: After a short halt (decline due to less testing) we see an increase in cases again. Also the positive rate is first time > 5% what indicates we must do more tests.
But: No = 0 increase in average deaths or ICU cases so far.
Many large clusters have occurred! Including schools, events etc..
Last Thursday I did travel by train during rush our. Ten thousands of people/hour cross their paths below the recommended distance without wearing masks. Where is CoV-19 really ?
GABA administration prevents severe illness and death following coronavirus infection in mice
- appears to reduce lung inflammation in general
- hopefully useful in influenza and pneumonia
https://www.biorxiv.org/conten…0.10.04.325423v1.full.pdf
Trial Site News - Oct-5
Real-World Evidence: The Case of Peru
"The correlation between the ivermectin interventions and the decrease in both mortality and lethality are quite strong and consistent in all the regions analyzed. However, this correlation could have been caused by other factors or as a product of an accident...The bottom line: treatment with Ivermectin is the most reasonable explanation for the decrease in the number of deaths and the fatality rate in Peru....
https://www.trialsitenews.com/…vidence-the-case-of-peru/
Whiteboard Doctor Video - Oct-5
Ivermectin And Carrageenan (IVERCAR) Prophylaxis: Intranasal And Liquid Dosing To Prevent COVID-19!
https://www.youtube.com/watch?v=TaPhpDmaG7I
Trial Site News Video - Oct-5
Clinical Trials and Research News Weekly Roundup | AdventHealth Ocala ICAM Protocol Takes on COVID
- includes discussion of positive Argentine study with ivermectin
TH,
How can “blood vessels leak and clot at the same time”?
As I understand it, the virus makes blood vessel walls everywhere leaky. It also makes blood sticky. Two separate mechanisms.
Many microbes (both bacteria and viruses) release or synthesize haemaglutinating toxins, causing blood clots whilst at the same time the immune system via cytokines etc attempts to exclude pathogens from the circulation by increasing capilliary wall epithelial membrane permeabliity.. This dual action is often fatal in sepsis. We need to block the cause of this (ie prevent the pathogens dividing or replicating) rather than focusing on treating the effects. And the dose-response relations clearly suggest that both ivermectin and hydroxychloroquine used together would probably potentiate their antiviral activity, in conjunction with other antivirals like D3, Zn, remdesivir and avigan. Whether the antibiotics azithromycin or doxycycline have direct antiviral actions is uncertain, I think these may be in part effective against secondary pneumococcal lung infections.
Swiss CoV-19 cases just reached US level!!
But: Hospital entries at absolute low since 4 months also ICU usage at least here in Zürich!
We finally go on to immunize the herd! And this also is a prove that aerosols stay longer at lower temperature/air humidity !
Here in France, there is a lot of talk about a new rapid test for SARS-Cov 19 which has just been authorized by the government:
https://www.huffingtonpost.fr/…_5f7b5d74c5b656cdfcc3502e
manufacturer's documentation:
https://www.skillcell-alcen.co…d-and-easy-molecular-test
This test is based on the “LAMP” technology (Loop mediated isothermal AMPlification) by Notomi et al. by EIKEN.
Notomi cites my patent (WO19960011327) on the first page of his patent, but he does not mention it in the text ...
http://www.google.com/patents/WO1996001327A1?cl=fr
Notomi et al. "LAMP" patent:
https://patentimages.storage.g…08f7bb379a8/US6410278.pdf
I think the EIKEN corp patent attorney cited my patent without commenting it in the text it just to prevent the patent office examiner from citing it himself. It's an industrial property trick. Sometimes it works.
Anyway, I never understood why they had complicated my method which worked so well with two palidromic "primers" by a method with 5 or six palindromic primers. Some ideas?
But hey, the bottom line is that this technology should be useful.
I am quoting this covid detection test and these isothermal amplification technologies because I noticed that the two heating steps to 65 ° C are not essential. In the case of my isothermal amplification method, I noticed that the reaction starts spontaneously at 20 ° C. It’s quite amazing. I think that this can be explained by the phenomenon of “Breathers”, which we also meet in the field of LENR: thermal energy is concentrated in certain places of molecules (in the case of DNA), or in certain places of the crystalline network (in the case of LENRs).
You have to remember that a DNA molecule, from my point of view, is a linear quasicrystal.
Display MoreI think the EIKEN corp patent attorney cited my patent without commenting it in the text it just to prevent the patent office examiner from citing it himself. It's an industrial property trick. Sometimes it works.
Anyway, I never understood why they had complicated my method which worked so well with two palidromic "primers" by a method with 5 or six palindromic primers. Some ideas?
But hey, the bottom line is that this technology should be useful.
I am quoting this covid detection test and these isothermal amplification technologies because I noticed that the two heating steps to 65 ° C are not essential. In the case of my isothermal amplification method, I noticed that the reaction starts spontaneously at 20 ° C. It’s quite amazing. I think that this can be explained by the phenomenon of “Breathers”, which we also meet in the field of LENR: thermal energy is concentrated in certain places of molecules (in the case of DNA), or in certain places of the crystalline network (in the case of LENRs).
You have to remember that a DNA molecule, from my point of view, is a linear quasicrystal.
Hi Fabrice, I hope that you are not upset about this patent (in that there is signficant overlap). I have some questions about the Covid19 primers - how do we know that they are an isolated match for Covid19 and not a former Corona virus?
In terms of the 20 degrees - I suppose that means the denaturing step is more efficient? What is the value and benefit of the lower temperature / concentrated energy? Are less amplifications needed?
Lastly, for most of the RT-PCR tests out there -- what do you think the false-positive rate is at various amplifications? Is there a way we can guess-timate this?
Swiss CoV-19 cases just reached US level!!
But: Hospital entries at absolute low since 4 months also ICU usage at least here in Zürich!
We finally go on to immunize the herd! And this also is a prove that aerosols stay longer at lower temperature/air humidity !
I'm not quite sure what is the case for Swiss exceptionalism.
from Worldometer.
7 day M.A. deaths (now) 2.5/day
number of new cases/day (Sept 15th 7 day M.A.) 416
IFR = 2.5/401 = 0.6%
That is absolutely in line with IFR everywhere else, including US, and it has not changed a lot - gone down a bit - through the pandemic.
Hi Fabrice, I hope that you are not upset about this patent (in that there is signficant overlap). I have some questions about the Covid19 primers - how do we know that they are an isolated match for Covid19 and not a former Corona virus?
In terms of the 20 degrees - I suppose that means the denaturing step is more efficient? What is the value and benefit of the lower temperature / concentrated energy? Are less amplifications needed?
Lastly, for most of the RT-PCR tests out there -- what do you think the false-positive rate is at various amplifications? Is there a way we can guess-timate this?
“In terms of the 20 degrees - I suppose that means the denaturing step is more efficient? What is the value and benefit of the lower temperature ?”
The value, it is that if the reaction works at 20°C without denaturation step, it could work at 37°C without denaturation step.
And 37°C is the body temperature.
Here is a useful guide to COVID-19 treatment:
https://www.covid19treatmentgu…w/management-of-covid-19/
It lists the acceptable range of oxygen saturation at sea level, which is higher than other sources. Moderate illness is >94%. Severe illness is <94%, and high respiratory frequency of >30 breaths per minute.
fabrice DAVID Your new rapid low temperature test sounds really encouraging, so it can be used by anyone without sending it to a lab? Is it possible to develop a test which will detect all the coronavirus variants because they have a high rate of mutation (by identifying non mutating, stable RNA regions which are common to all the bat coronavirus sub-species)?
