Guest post by Rud Istvan,
Rumination #5 developed possible explanations for two emerging observations:
-Why more CVN71 sailors did not test positive for the Wuhan coronavirus because their adaptive immune systems were not naïve;
-Why hypertension, diabetes, and obesity are the main NYC comorbidities in the serious/critically ill under age 65 CoViD-19 patient cohorts.
This guest post extends those two ideas to new observational information about antibody testing, and a very recent mainstream media (MSM) observation that an abnormally high percentage of ICU CoViD-19 patients have various forms of thrombosis. As with guest post #5, there is a high reliance on the medical literature searchable at www.ncbi.nlm.nih.gov. The most relevant literature is referenced in what follows by PCM number. For those interested in further personal research, this post also provides key words and concepts for Google exploration.
Naiveté and serologic antibody testing
CVN71 sailors were tested for Wuhan virus using PCR, which looks for the active presence of Wuhan RNA. About 15% were positive; the remainder had no evidence for the virus despite the extreme ‘lack of social distancing’ that concerned the Captain so much he was removed from command. The naiveté hypothesis speculates that (recent) exposure to the four common cold coronas may have conferred a degree of Wuhan immunity; much like vaccination with cowpox provides immunity to smallpox. This would be especially true for the two ‘beta’ serotypes OC43 and HKU1, as Wuhan is also a beta serotype. This hypothesis would also explain positive but permanently asymptomatic cases (20% in South Korea); a weaker (older common corona cold?) but still a sufficient timely response by the alerted adaptive immune system.
BUT, if true, then this hypothesis also presents a potentially seriously confounding factor for the serologic antibody tests now being developed–so far with little to no regulatory oversight or rigorous independent evaluation. To the point, Roche’s CEO said publically last week that many of these ‘would be of no or little value’. To understand why requires three background science ‘facts’.
First, the antibodies being tested for come in two flavors. IgMs form early and decline ‘quickly’. They say you recently had the virus, but do not confer lasting immunity. IgGs form starting about 10 days into a viral infection, peak at about 21 days after infection, and are what confers any degree of lasting immunity.
Most of the antibody tests being developed are qualitative ‘color changing’ lateral flow tests for IgM, IgG, and a control strip (which if it does not change color means the test failed). They are the same in operating principle as home pregnancy test kits.
Second, these antibodies can work in two ways. The ‘minority’ way is as a ‘neutralizing’ antibody that binds to and directly inactivates a virion in some fashion. This is the hope behind the convalescent plasma treatments now in clinical trials. For coronaviruses, there are three targets that potentially neutralize:
- The N protein (the nucleocapsid coat) which, when interfered with by a neutralizing antibody, prevents the encapsulated RNA from ‘extracting itself’ to enable intracellular replication. As a sub-result of a separate pulmonary study concerning influenza, 105 adults with COPD were tested for N antibodies to the four common cold viruses. 104 tested positive to 229E, 105 to OC43, 103 to NL63, and 96 to HKU1. VERY HIGH. The Wuhan N is likely to be similarly highly specific, a good thing for serologic antibody testing as explained below.
- The S (spike) protein, which has two neutralizing antibody binding sites, S1 (the ACE2 receptor), and S2, which varies by serotype. S1 lets the virus latch onto a cell, after which S2 enables the virus to enter the cell. The problem is that Wuhan uses the same S1 for ACE2 as the common cold coronas—hence the naiveté hypothesis.
The ‘majority’ way antibodies work is just ‘binding’ somewhere to some protein fragment. Corona has M (membrane), E (envelope), and S other than S1 and S2 as possibilities. These do not inactivate the virus, but do signal adaptive immune system cells to eventually come clean up as they multiply in response. There has been a fair amount of work on the original SARS, showing that alveoli macrophages can ‘ingest and get infected’, but that the virus cannot replicate inside the macrophage. A ‘cleanup needed on isle 3’ announcement mechanism. What is not yet available in the literature is how similar/dissimilar these binding antibodies might be between the common cold coronas and Wuhan. The more similar, the more likely both IgMs and IgGs will be insufficiently specific.
Third is the sensitivity and specificity of the resulting antibody test. Sensitivity is how many true positives are missed. Specificity is how many false positives are generated. As of now, only a few manufactures have offered their internal (unverified by the FDA) estimates based on small samples of people. As one would expect, results vary. Becton Dickenson says their new test is 88% sensitive and 90% specific. The importance of this requires using the formal probability mathematics of Bayes Theorem. As an example from a very new clinical lab article, if you assume the true prevalence of Wuhan is 5%, then a 90% specific antibody test (BD as advertised) will produce 70% false positives and be essentially useless for CFR denominator and herd immunity purposes. (Evaluation.com, an on line journal for clinical labs, Cairn article from 4/22/20)
Unknown is how sensitive and specific these tests can be made by careful antibody selection. The widely cited new Stanford paper on 3300 Santa Clara residents said it used a lateral flow test of both IgM and IgG from Premier Biotech in Minneapolis that it had independently validated in a small sample as a combined (different methods) 80% sensitive and ~99% specific– without separately checking for common cold corona N. So I checked Premier. Turns out they are only distributing a test from Hangzhou Biotest Biotech, Ltd. And Biotest’s Chinese website doesn’t provide specificity and sensitivity estimates at all; the specifications page is blank.
The Roche CEO is correct—we have a ways to go yet with antibody testing.
Thrombosis
This deadly ‘new’ complication has been much in the news in recent days after Broadway star Nick Cordero, age 41, had to have his right leg amputated as a result of CoViD-19 induced deep vein thrombosis. Media reports are that the incidence is between 20-25% of all ICU patients. This could certainly be a further explanation for the number of cardiovascular deaths from ‘heart attack without atherosclerosis’ pointed out in #5.
One possibility is that propensity to clot is known to be disproportionately high in those with diabetes and hypertension, so just another sequelae of obesity. But Cordero was not obese and reportedly healthy, without hypertension or diabetes.
There is another. PMC3809294 points out that platelets must have roles in addition to clotting. The paper estimates that thrombosis requires about 10E+9 platelets/liter of blood, while typically there are about 250E+9 per liter. To initiate clotting, platelets must be ‘activated’. PMC6048695 says that it is known that interactions between platelets and viral pathogens results in activation via plasma proteins called kinocidins. And finally, newish PMC4270245 has a detailed mapping of platelet activating receptors. It turns out that common cold coronaviruses directly active platelets via receptor GPV1, and that IgG antibody/antigen pairs directly activate platelets via the FcyR11 receptor.
As a result of this new knowledge, it would appear that adding an anticoagulant such as clopidrogel (Plavix) should become standard prevention therapy in serious/critical hospital cases. There is however as of today (4/23/20) no medical consensus on that, any more than about hydroxychloroquine plus zinc as a treatment therapy.
Since viruses mutate, is there a possibility that each n-th generation may be a) less or b) more infective ?
a) virus will after period of some months naturally extinguish itself
b) return in far more deadly second go (as in the case of the Spanish flu)
Considering that incubation period appears to be (on average) less than two weeks, current infections would be at least six to ten generations removed from the ‘bat woman’ case.
Is there any information in the genome differences between the current and the early viruses?
Answer: yes. Although the tendency is that severer mutations ‘burn out’ sooner while ‘milder’ mutations can hang around forever.
Answer: yes. Just published is a study showing ~40 mutations in just 5 months since the beginning. More severe Europe from China, and NY came from Europe. Less severe West coast from China.
Implication: the eventual vaccine may end up having the annual flu vaccine hit or miss mutation problem. Wuhan and flu are both RNA viruses. Explained in my first post on this topic.
Thanks Rud, despite me having a very little knowledge of the matters bio-medical, I find your reviews help greatly in comprehending the complexity of the subject. Thanks again.
RNA mutations are meaningless as long as they don’t interfere directly with the host defenses’ or changing the amino acid sequence of the viral proteins that result in modified features. That actually is less likely for most viruses as one would think just because most mutations are detrimental to the virus and not beneficial.
I bet the genetically engineered vaccine approaches are designed to target the parts of the known substrains that have no mutation at all.
“RNA mutations are meaningless…”
Again, a thought totally unaware of the last 15 years of the RNAi revolution, and RNA structure function discoveries.
It seems sufficient to infect 60% of the population to get the virus “tamed”.
depends on R0
Rud,
I read this post of yours, not very intently, but the idea I got is the consideration of the overall picture discrepancies and especially the antibody test.
Let me say this first;
any tests viral plus antibody, properly productive and assisting for better understanding of the condition if applied properly during the disease period.
The viral test completely useless when clearly outside the disease period, while the antibody tests usually
still holding some value even outside the disease period.
But sometime in special cases the antibody test still in proper value if the antibody that it tests for continues to be active even after the closure of disease period.
You will see a lot of fights, very bad vicious ones against the antibody test for COVID-19, due to the persistence of corresponding antibody.
First because the delaying, gains nothing,
Second, because maybe the preliminary applications for the validation of this test may already show a very
scary panicking results, where a considerable (high) number of sufferers for COVID-19 have not the corresponding antibody.
In consideration that the antibody persist and does not go away, and when many diagnosed with COVID-19 do not have it, then the Occam states that most of COVID-19 disease, including severity and fatality of this disease, not caused by this new virus or this new virus infection.
Quite strong, but hey there is a reason for the antibody test and it’s great support for seeing through the “dark”… it is a strong fundamental procedure.
You “kill”it, for whatever reason, you do not learn, “history” keeps repeating.
HIV does not cause the pneumonia disease.
Similar with COVID-19… not the same though, but similar.
Second there is two antibody responses to the same virus as it causes two diseases.
The throat disease, and the lung disease.
Clearly showing that the antibody response is to the disease not the virus perse.
Meaning, that simply being infected, it is not a given for an antibody response, not always.
Also indicating, that the disease, the termination of the incubation period may fail to trigger a immune response, due to the fact that the disease in not the only disease happening at the same time, and most probably the not prevalence one at the time.
Again antibodies do not fight viruses… at least not directly… the immune response is to the disease not to the virus, even when triggered and upgraded by the virus.
Life is stranger than fiction… greatly far far much beautiful.
cheers
Antibodies respond to pathogens, not to the disease they cause.
An antibody (Ab), or immunoglobulin (Ig), is a large, Y-shaped protein produced by plasma cells. The immune system uses these proteins to neutralize pathogenic bacteria and viruses. Via its fragment antigen-binding (Fab) variable region, the antibody recognizes a unique molecule on the pathogen, called an antigen. Structures on each end of the Y bind precisely with with corresponding features on the antigen, like a lock and key mechanism. This bonding allows the antibody to tag the pathogen for attack by other parts of the immune system, or direcctly neutralizes its function.
Antibodies fight the disease by attacking its causative pathogen, or nip them in the bud before an infection can develop into a disorder.
John Tillman
April 24, 2020 at 11:27 am
John, hypothesis explanations and being stubborn about such as can not contest clear facts.
Same virus two different antibodies, simply because two different diseases, one of the throat and one of the lungs, different tissue diseases, different antibody response…in the case of the SAME VIRUS… where the antibodies do not have also the same response time parameter.
Fact, not hypothesis or academic hipper convulsive explanations.
Antibodies, and the rest of the immune system responds to clear the disease, the pollution from the disease… even, again, when the proper response most of the time triggered by the virus.
Now, as for hypothesis and guess explanations:
“or nip them in the bud before an infection can develop into a disorder.”
It is more like “nip them in the buttocks” by going for the pants, effectively, before the infection develops into considerable dysrhythmia… by striping them off and have them naked facing the harsh environment there.
Wrong response, non efficient antibody response, leads to infection dysrhythmia, triggering an ever increasing aggressive response from immune system.
External artificial factors effecting the overall immunity to the condition of seasonal dysrhythmia, lead to the wrong seasonal infection, to a more harmful one, due to dysrhythmia of overall
immunity.
Overall immunity consist as the immune system response and/+ the natural body efficiency of blocking and suppressing of the most “looser” but more “aggressive” dangerous viruses and the
infection-disease from such as.
Oh well, just hypothesis this second part…
Thanks for your reply, John. Appreciated. 🙂
cheers
“Same virus two different antibodies, simply because two different diseases, one of the throat and one of the lungs, different tissue diseases, different antibody response…in the case of the SAME VIRUS… where the antibodies do not have also the same response time parameter.
Fact, not hypothesis or academic hipper convulsive explanations.”
My apologies but this is just plainly wrong.
There is always more than one antibody developed upon an infection. But that has nothing to do with the tissue where the infection is happening. The B-lymphocytes circulate through the whole body via the lymphatic system to ensure the antibodies are available everywhere. That is why you can get antibodies for testing from the blood where you can’t do the same for the virus as it’s not replicating there sufficiently for testing.
Ron, this is amazing.
You, are a guy who have a specific antibody, without the virus, without the infection, without the disease… still fully active.
Do you think your immune system is stupid or silly on keep activating fully that antibody? (without the virus present)
Do you think that immune system response and antibody response exist primary due to response to infection and diseases?
Ok, name a virus that you know, apart from this novel one, that does have in it’s belt the consideration of two antibody responses.
Am not saying that this the only one, or that it is not the norm, but with this one is very clear, simply due to different time parameter response of the antibodies, which does not overlap and still corresponds to two different diseases, which connect but do not overlap.
(or at least that is how I know it to be, in consideration of the data there;
please feel free to correct me in this one if I have got it wrong)
Are you saying that this virus causing two different diseases is a myth or an urban legend… or some made up staff?
Do you know of any other virus that causes two different diseases corresponding and linked to each other as per the matter of full infection path?
Yes there is a huge “melting pot” of infections and diseases there, a huge messy
“antibody pot”, but failing to learn from the specifics and clarity of this novel
infection-disease, when the fact is clear, but we don’t like it or appreciate it, is quite amazing.
There is two antibodies in case of this virus, because of two different infections and two different resulting diseases.
That is the fact you are contesting, not me.
I simply concluding, with the only conclusion left there, in accordance of this fact;
Two different antibody responses due to two different infections (not one infection) resulting in two different diseases (not one disease), of two different tissues.
Response to the disease (“death”) not the virus.
(any “death” has it’s own signature, the best response, including antibody, is tied to that signature,
and again, please do feel free to correct me, if the fact in question not a proper one, or a result of misunderstanding in my part. )
Now again, as per hypothesis and guesses;
Your artificially acquired antibody still fully active in you, due to it being the best your immune system knows for dealing with a certain signature of “death” in your body,
even when that “death” not due to the corresponding infection-disease of that antibody.
The contiguous cellular death in the liver… which happens continually over time… regardless of a specific infection-disease.
The immune system does not do lock downs, isolation, “social distancing”, or disinfection.
The closer thing to “disinfection” is a last resort full response,
a heavy “incineration” of
the locality with the problem, meaning severity and high chance of fatality…
usually, sometimes, triggered by “confusion” and “misreading” of the condition.
Again this second part of my reply to you hypothetical, or a guess.
Please do not confuse it with what considered as fact in this comment of mine.
Please you do not need to apologize Ron.
We just engaging in a public conversation.
And I am prone to error and mistakes as much as the next one or anyone.
And you being very civil, and cool. 🙂
Ron, no hard feelings on my part, and appreciated.
cheers
You need an infection first otherwise no antibody.
Every antigen creates different antibodies through different lymphocytes. Always. This a singular event for each lymphocyte so there are a lot of different antibodies generated. You can actually isolate those different cells cause they have the capacity of replicating and generating clones. Then each clonal cell just produces only one specific antibody whereas the serum of the patient is full with a load of different ones.
Please read https://en.wikipedia.org/wiki/Memory_B_cell about how the body manages to keep information of earlier infections. For each antigen many different cells are stored.
These cells are either continuously expressing antibodies that can be directly detected or you test the immunity by challenging the present cells in a blood sample with the antigen in question to create more antibodies and measure those.
“Are you saying that this virus causing two different diseases is a myth or an urban legend… or some made up staff?”
Pathogens can cause different symptoms in different tissues. Sometimes tissues are prevented from being exposed to the pathogen through barriers and the pathogen usually has one specific list of symptoms in the tissues it can easily reach. Does the barrier get compromised for whatever reason the pathogen can cause another list of symptoms in different tissues.
But that does not mean it’s a different disease. It is a different list of symptoms but still the same disease. So if one would have working antibodies from one or the other list of symptoms in one tissue one would be immune to the other list in another tissue in case of a second infection. Antibodies are recognizing the pathogen not the symptoms.
The traditional clinical classification of diseases by symptoms is actually a mess. There are “diseases” that have a lot of different underlying causes but have been defined as the same based on the symptoms they share where other “diseases” have been classified as different ones though they have the exact same underlying cause but different symptoms. But these things are rewritten as knowledge grows.
I hope this clarifies things.
Ron
April 24, 2020 at 8:31 pm
Thank you Ron.
I see your point in your reply to me.
But still, your explanation based in whole this messy hypothetical and terminology,
still does not explain a fully activated antibody without the disease or the symptoms.
You still have not refuted the validity of the fact, there, just tried to explain it away due to mostly terminology, the terminology of symptoms versus disease.
I get the attempted rationale there, by forcing a point in the consideration of terminology, but still find it wrong.
The school of thought you rely at in this case, propagates in consideration of cancelling out a conclusion due to terminology invalidating the fact… like in the science of AGW.
The conclusion based in consideration of two different diseases not valid, according to your rationale, because of the clause of symptoms.
where no symptoms no disease, or no significant symptoms no disease to consider, or no good enough to consider it.
Clear symptoms, as by the book, then disease to consider.
Ron there is stronger symptoms solely due to certain vaccinations, far far much considerable than in most of non hospitalizations of COVID-19, and same or even clearer in case of the other disease of this novel virus, the throat disease, which does not have even a name yet… as it can not be called a COVID-19, as that happens to be a lung disease.
According to your rationale should we reclassify such strong symptomatic conditions due to certain vaccines as diseases?
Actually, Ron, such strong symptoms have nothing to do with the meaning of disease in reality of life and nature.
Disease consist as a condition of excess cellular death in the body, regardless of the symptoms, where symptoms are simply an indication of the disease due to the immune response, where sometimes the immune response to a disease does not result in detectable or orthodox specific symptoms…
Again we are talking about viral infection-diseases, no need to pollute the argument by generalizing disease in relation of other conditions.
I am not against orthodoxy, for as long as not overdone and therefor leading to contradictions
Ron, a very clever way on trying to invalidate a conclusion by explaining away the fact as with no much value by merit of terminology, by refusing the condition of the disease clause.
Ron, refreshing your memory;
“There is always more than one antibody developed upon an infection.”
That was your refutation.
And the fact is related to two antibodies due to two different infections, throat and lungs.
My point;
“There is two antibodies in case of this virus, because of two different infections and two different resulting diseases.
That is the fact you are contesting, not me.”
If the orthodoxy proposition of terminology of symptoms V disease, prohibits you to consider the resulting condition of two different infections as diseases in this case,
still the fact stands valid, as far as I can tell.
and I can not see for best of me any other valid conclusion in that regard, can you?
Besides, the antibody function consist of another major importance in the case of the immune system responding to “death” clause and disease.
As the main information platform for the immune system communication, in alerting, measuring, tracking, “monitoring” and scaling up or down the response to the condition.
No efficient or the wrong antibody activation, will very much jeopardize the whole response… where the performance of the immune response depends a lot in the performance of the antibody… very important in disease condition, the excess “death” of cells… where response is to the condition not the symptoms, where symptoms are an outcome of the response.
Hopefully being clear enough, at least at the point that the argument offered is understood.
The only way to properly invalidate the fact is by showing that it is not real,
where the two antibodies in this case are related to only one infection and resulting condition, the lung one, the COVID-19 as known,
and have nothing to do with the throat infection… simply solely both localized as a response to the lung infection.
There made easy.
cheers
whiten, I try to be as non-redundant as possible:
Antibodies are produced against pieces of the virus. These pieces are generated from chopping the viral proteins. This mechanism is not any different between tissues. As the relevant pieces of the virus on its surface are also not any different between tissues an antibody that works in one tissue will work in another.
The immune cells that are producing antibodies are maturing outside of the site of infection. Then they are invading back again.
So there is mechanistically no way that antibodies from different tissues are any different by a directed mechanism. They can differ just by chance though but that they do anyway between different people with exactly the same site of infection and symptoms.
With your other points I have to admit that I really don’t get what your hypothesis is.
Ron
April 25, 2020 at 5:23 am
Ron thank you again.
Nice conversation, but you have to understand, the main point is the piece of fact.
I am much interested on it’s validation than the theories or hypothesis contesting my conclusion.
I am not sure how true and correct or valid that fact is, the rest is not that important to me, not that I do not enjoy the discussion of hypothesis.
But any way, as you so much in hypothetical contest discussion, let me tell you that your hypothetical understanding of how antibodies are produced against pieces of the virus, can not be more wrong than that… totally backwards.
The immune cells produce the antibodies.
No virus info will be used to produce unless the “receiving address” on the envelope of the virus is that of a human cell, that immune system “knows” and has a record.
The pure other species viruses have a non human cell “receiver address” which the immune cells are not interested at, as it is with no meaning.
“Sender’s address” in that envelope does not matter if it is unknown (foreign), either to immune cells or
the human cells that get infected by the virus.
A known virus to immune cells does not get a second chance to enter the immune cell, unless the “receiver’s address” is that of the immune cell, like in the case of HIV.
The key that unlocks a cell to a virus, for infection, is the matching of the actual cell’s “address” with “receiver’s address” on the envelope of the virus.
Again the sender’s address being non human does not matter much.
The COVID-19 virus has a double “sender’s address” (Pangolins, Bats, both far much older species than humans) and
a double “receiver’s address” throat, lungs.
In my understanding, two different “sender’s addresses” in the “envelope” definitely mean two different “receiver’s addresses” in that envelope,
aka two different infections and to different possible diseases.
Meaning, if there a COVID-19 disease, a lung disease there should be another
COVID disease, like for the throat,
kinda of called COVID-17 or even maybe COVID-16. 🙂
The immune system cells do not care at all about the inner content of a virus unless the virus has a “receiver’s address” matching that of the immune cells.
The “senders address” has only one meaning, utilized as confirming for only to block more than a same virus getting access to a cell, either in the case of immune cells or other human cell.
It is only one penetration only once, of a given virus into a given cell, regardless,
same as in the case of a spermatozoide, the life infection. 🙂
A double “address” virus will infect two different types of cell’s, triggering a double antibody response for each different cell infection and disease.
So the antibody production is all about the info on the virus envelope and time parameter response + the specific physical properties of the virus.
Oh well, I like my hypothesis better than your hypothesis, must confess. 🙂
But still the main point of my interest is further proper validation of the fact,
or maybe the presumed fact.
And as per this:
“As the relevant pieces of the virus on its surface are also not any different between tissues an antibody that works in one tissue will work in another.”
Yes, in most cases,
“an antibody that works in one tissue will work in another.”
Key, point though, only the proper corresponding antibody has the proper efficiency.
One of the points I raised in the earlier reply to you, was about the antibody efficiency.
Where a different antibody will work in the same disease, but will be not as efficient, as the proper produced corresponding antibody to the given disease.
Where activation of not the proper antibody, could be so wrong due to the lack of required efficiency, that it could very much mean the difference between life and death in such circumstances.
The immune system, due to life experience grows the antibody “library”, where there always are groups and classes of antibodies that work on the same cell tissue, respectively, in consideration of the same disease, but with different parameters of response and physical characteristics… as in consideration of time parameters and physical attributes of the virus responsible for infection-disease.
Activation of an antibody, with low efficiency in consideration of a disease, is quite very dangerous…
Oh, well Ron, hypothesis and theories have a strange history, of a colossal failure.
🙂
So I am not claiming any thing different than that historical fact.
But you see, fact and conclusions are a different matter, much easy to validate or invalidate. No much fuss there, either it is or not valid or true can very easy checked.
And some time, some conclusion can be indisputable in consideration of a valid fact, as the only one true to the meaning of the fact.
Again, appreciated… 🙂
cheers
“The B-lymphocytes circulate through the whole body via the lymphatic system…”
Mostly correct Ron, and I do not want to distract from the point you are making, but I do want to point out that the network of lymph vessels is a one way street, returning fluid from the interstitial spaces to the heart.
These vessels gather interstitial fluid (which contains the portion of blood plasma which exits the blood from capillaries and is not reabsorbed back directly into blood capillaries,) from the various tissues of the body, and move it towards the reentry points into the blood stream, via the subclavian veins.
B cells, like some other types of immune cells, can move to the sites of injury or infection by chemotaxis.
At any given time the vast majority of our immune cells are residing in tissues, not in the blood.
And it seems likely (to me anyway) that they can even pass directly through cells, as well as than between them, since at many locations the cells have tight junctions. This occurs when the cells have to pass out of the circulatory system and enter the interstitial spaces, a process called diapedesis.
In this process, called trans-cellular migration, leukocytes cannot pass between the cells of the epithelial lining, so they pass right through them: The cells are first invaginated and the migrating cell enters this invagination, which then closes behind the migrating cell and opens on the other side.
In fact this once controversial idea is now being elucidated and demonstrated to be occurring.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811962/
See also this interesting video, ten craziest things cells do:
https://youtu.be/ooA0J6DWWTM?t=462
Sorry about the digression, but it should be understood that the lymphatic vessels are not a circulatory system. More like a drainage system with many critical functions built into it.
Sweden is about to close restaurants now.
Those that do not comply with distancing rules.
https://www.reuters.com/article/us-health-coronavirus-sweden-stockholm/sweden-to-shut-bars-and-restaurants-that-ignore-coronavirus-restrictions-idUSKCN2262AX
Sweden may CLOSE bars and restaurants if people keep ignoring social distancing.
Is this what you are referring to? Do you have a good link?
I did my bi-weekly grocery shopping today. About half the customers were not wearing masks of any kind. They mostly seemed to be young people. Ohio is set to loosen restrictions in about a week, but still recommending masks. I think that two weeks ago there were more customers using masks than there were today. Ohio has about 600 deaths with a population of 12 million. I’m not sure that everyone is taking this seriously.
Starting monday, we have to wear masks in all shops and busses etc. (Germany)
Having been a painter I can tell you that the majority of masks are about as useful as tits on a bull. Where they do make a difference is when someone coughs or sneezes the mask stops the air shooting out at great force directly in front of that person and is diffused around them so may not travel as far. I also see people using the same mask time and time again which would also reduce their effectiveness. The nose is extremely efficient at filtering things out so breath through your nose and not your mouth. Years ago I heard of someone that was heavily medicated for asthma but they forced themselves to breath through their nose as they slept and within about two weeks were off the heavy medication.
That may be reason enough, there are certainly lot of people that don’t know they are spreading. Not that I like masks and not that I’m not aware about what you said concerning their ineffectiveness. But I realised, that other people in shops stay at distance 😀
More men die than women. In general, men have significantly more red blood cells than women. When the body’s cells are destroyed during a virus attack, free heme enters the blood, leading to blockages.
You are not very specific. Red blood cell per microliter:
men 4.7 to 6.1 million
women who aren’t pregnant 4.2 to 5.4 million
Waste your time as you please, but please don’t waste my time.
Thus, the average for women is 4.8 million, and for men 5.4 million red blood cells.
So women have 12% fewer blood cells. Not very significant.
Less blood cells and less iron due to menstration?
This applies to women up to age 51 (statistically).
Free Heme Toxicity
In contrast to the positive functions of heme, free heme excess can cause cell damage and tissue injury since heme catalyzes the formation of reactive oxygen species (ROS), resulting in oxidative stress. Heme that is not bound to proteins is considered the labile heme pool; this portion of heme is derived from newly synthesized heme that has not yet been incorporated into hemoproteins, or heme that has been released from hemoproteins under oxidative conditions. “Free heme” is an abundant source of redox-active iron that can participate in the Fenton reaction to produce toxic free hydroxyl radicals. ROS damage lipid membranes, proteins and nucleic acids, activate cell signaling pathways and oxidant-sensitive, proinflammatory transcription factors, alter protein expression, and perturb membrane channels (Vercellotti et al., 1994; Jeney et al., 2002). Heme toxicity is further exacerbated by its ability to intercalate into lipid membranes. Due to its lipophilic nature, heme may initially lodge within the hydrophobic phospholipid bilayer. Within this highly oxidizable matrix, iron catalyzes the oxidation of cell membrane and promotes the formation of cytotoxic lipid peroxide, which enhances membrane permeability, thus promoting cell lysis and death (Balla et al., 1991; Ryter and Tyrrell, 2000; Kumar and Bandyopadhyay, 2005; Tolosano et al., 2010). Additionally, heme is a potent hemolytic agent. It affects erythrocyte membrane stability as a result of ROS formation and oxidative membrane damage. Finally, heme is strongly pro-inflammatory since it induces the recruitment of leukocytes, platelets and red blood cells to the vascular endothelium, it oxidizes low-density lipoproteins and it consumes nitric oxide, thus impairing vascular function.
https://www.frontiersin.org/articles/10.3389/fphar.2014.00061/full
Release of heme as a result of lung cell destruction and oxidative stress may explain the frequent sudden deterioration of the patient’s condition around day 10 of the disease.
Women live longer on average and have lower all cause mortality than men, and working on ladders over stairwells (for example) is only a tiny part of the reason.
CPT Crozier was relieved of command of CVN-71 for widely distributing his communication over a “non-secure, unclassified” email sent to “20 or 30” additional recipients, beyond his immediate superior, the RADM commanding the Carrier Strike Group centered on USS Theodore Roosevelt.
The Navy and Navy Department are considering reinstating him.
There wasn’t much the sea service could do to help the ship out, except for what it did, ie divert TR to Guam and try to find hotel rooms there to quarantine crew.
Crozier says he chose to let sailors go ashore and to take on stores there because he was told that the virus had only been found in northern VN, not the center. But clearly it already was in Da Nang. TR steamed into Da Nang with just one escort. The rest of the strike group stayed away.
As for shore leave in Vietnam. Back in the late 60s and early seventies there was a deliberate effort to spread desease to the troops.
Why is it such a stretch to see that this might have been deliberate…
They should never have been allowed to leave the ship.
The U.S. Navy is now indicating they might reinstate Captain Crozier. I think this would be a huge mistake if they did. They will be sending the wrong message to the troops and everyone else. I wouldn’t have any confidence in a Naval Chief who would reinstate this man to his former position. I wouldn’t be the only one, either.
The CNO went along with Navy Department’s civilian political appointees, despite his having served as a Carrier Strike Group CO. Three and four star flag officers must often act as politicians in uniform. They almost never resign out of disagreement on principle.
CPT Crozier violated both operational security and the chain of command. He was rightly sacked, IMO.
He was relieved of command for sending a message to a few dozen people, a message that would be leaked, by someone who made a speech with improper language to the whole crew (thousands), not expecting that it would be recorded and leaked… lol
“As a result of this new knowledge, it would appear that adding an anticoagulant such as clopidrogel (Plavix) should become standard prevention therapy in serious/critical hospital cases”…
Clopidogrel is not an anticoagulant – it is an antiplatelet. This distinction is often muddled, but I wonder if it makes a difference in this application, since both antiplatelet and anticoagulants are antithrombotics.
Mods, I have one or more comments in moderation.
Thank you.
A slight diversion – but something that has been puzzling me. Maybe someone on here (Rud??) has some insight:
I think it is agrees that the way the virus infects human cells is via the ACE-2 receptors.
I have seen claims that ARBs (Losartan, Olmesartan, etc.) might:
a) Make matters worse.
b) Provide some protection.
I can see the protection happening. Maybe, depending on how these drugs work. They block angiotensin-II from attaching to the ACE-2 receptors — how? Is if interfering with the angiotensin-II itself? Or does is somehow “mechanically” block the receptors (by attaching to them itself??). If its the latter, I can see it interfering with anything that tries to attach, including the covid-19 virus.
The claim that it could make people even more receptive to the virus I just don’t see … well, maybe … if the ARBs work by interfering in some other way that directly vlocking the ACE-2 receptors – which I suppose could leave more of the “open” for attack?
Anyone have any words of wisdom on the subject?
As I understand it…
Increased ACE2 expression likely increases risk of severe infection simply due to the increased number of infection points. Infection increase decreases ACE2 expression.
ACE triggers inflammatory factors; ACE2 triggers anti-inflammatory factors. They counter-regulate to maintain RAS homeostasis.
ACE inhibitors prevent ACE from converting angiotensin I (AngI) to AngII. AngII mediates inflammatory response through the AT1 receptor (AT1R).
ACE2 converts AngII to Ang(1-7), which mediates anti-inflammatory response through the Mas receptor.
ARBs block AngII from attaching to AT1R preventing mediation of inflammatory response.
IMO the worst thing that doctors can do is take covid patients off of their ACE inhibitors and/or ARBs because that will allow more AngII to attach to AT1R and increase inflammation.
There is a clinical trial for an ARB to treat COVID.
People taking any ACE inhibitor have a substantially reduced lifetime chance of ever getting pneumonia or any reason.
I wonder how many people went off a A.I.’s after reading speculation from people taking WAGs based on no actual evidence or logical reason, but instead internet and social media rumormongering?
It becomes less astounding after such events that authoritarian guvs and dictatorships throw people in jail for spreading rumors.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394697/
Thanks for comments and link. On ace inhibitor myself.
I am trying to track down original source to stop using.
The “original” was probably the letter to The Lancet by some European researchers. It mentioned that ibuprofen also increases ACE2 and mentioned calcium channel blockers as an alternate treatment to ACE inhibitors. You might be able to find it based on those keywords.
This is what started it all
Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext
It’s pretty accepted that increased ACE2 expression increases severe infection risk. Doesn’t take a genius to see that increased infection points increases risk of infection.
ACE inhibitors may decrease risk of pneumonias per your study, but most pneumonias are bacterial, which have nothing to do with ACE2; so the data in that study are skewed.
Other drugs control hypertension. ACE inhibitors aren’t used much in E Asian countries. So moving from ACE inhibitors before infection to something else that controls BP, but doesn’t increase ACE2 expression seems like a prudent thing to do. That’s what I would seek to do.
However, stopping ACE inhibitors after infection is IMO possibly the worst thing to do because that would push RAS towards its inflammatory axis.
My study?
Skewed how?
It is a look at 37 longitudinal studies and data was mined.
A so-called meta-analysis.
Did you even look at it?
You speak in absolutes a lot, and after starting with “As I understand it…”, then remove any qualifying remarks, and by the end you seem to regard your understanding and mischaracterizations as some sort of bedrock human knowledge.
I never do that.
This was a study looking at a giant number of people from all over the world, and one of the analyses was all cause pneumonia.
All cause.
Do any of the people dying of COVID have bacterial involvement?
You seem to dismiss the entire notion, but you have also many times indicated a belief that the z-pak treatment is proven effective.
From “my” study:
“What is already known on this topic
Angiotensin converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with cardiovascular disease
These drugs also have secondary effects on the respiratory system, suggested to protect against pneumonia
Most of the data on this issue are provided by heterogeneous observational studies with inconclusive results
What this study adds
In pooled results from both interventional and observational studies, ACE inhibitors, but not angiotensin receptor blockers (ARBs), showed a statistical and putative clinically significant protective role against pneumonia
This result may discourage the withdrawal of ACE inhibitors in patients with tolerable adverse events—namely, cough
This protective effect was higher among Asian patients and in those with previous stroke; patient populations that may benefit most from ACE inhibitors.”
Yes I read it the first time you posted it a while back, and and realized then that it doesn’t support what you say it does. You can’t extrapolate from that study that ACE inhibitors protect against pneumonia caused by a virus that targets ACE2 because most pneumonias are bacterial, and bacteria do not infect via ACE2. The data are naturally skewed towards bacterial pneumonia, which ACE inhibitors may protect against. But your assumption based on that study that ACE inhibitors protect against coronavirus pneumonia is just wrong.
I reached no conclusions.
You did that.
I post evidence, and this study was only one of many pieces of evidence I have looked at.
I post evidence.
You make unsupported assertions.
You mischaracterize what others say, and rewrite your own opinions and in fact medical textbooks on a daily basis, based on what no one can say, because you never do.
icisil
April 24, 2020 at 5:12 pm
I have followed your ACE ACE2 relation explanations and conclusions.
It has being very interesting to me.
I understand (I think), your point:
“You can’t extrapolate from that study that ACE inhibitors protect against pneumonia caused by a virus that targets ACE2 because most pneumonias are bacterial, and bacteria do not infect via ACE2.”
I am just trying to learn about this specific detail.
But I am still trying a figure out the consideration of the virus targeting ACE2.
Outside the hypothesis or virtual scenarios, what actually in consideration of data and observations support this conclusion as put?
Is this a colloquial expression of the given condition, or is it hands on observation?
Indication of a strong correlation between a successful viral infection and the imbalance jumping in favor ACE versus ACE2, does not strictly mean the virus targeting or utilizing ACE2, I think… unless the targeting and utilization observed, clearly.
Is any data there that support such as, in consideration of petri dish experiments?
I do not know much of this only trying to learn and understand it better.
thanks
whiten, I have no idea how they know what they know, but apparently this coronavirus, as well as the first SARS coronavirus, has spiked proteins that attach to ACE2 enzymes on cell membranes, and infects cells through that portal.
Hope everyone sees this concerning ace inhibitors.
Yes there has been controversy on this subject. The latest recomendation(which has changed):
Keep taking your you ace inhibitor..
Will be disscusing with my Dr next week to verify.
Directly from the EVMS team
It would be interesting to know at some point what number of fatal COVID-19 victims had a type of blood condition known as Factor 5 Leiden? Patients already diagnosed with such might be on some sort of blood thinner that limits thrombosis and hence avoid the clotting issues that can lead to heart failure. Or in the reverse, how many victims of COVID-19 perhaps had undiagnosed Factor 5 Leiden that led to clotting and all those issues that present in deep viral pneumonia and/or heart disease, perhaps much sooner with the addition of COVID-19. Maybe something like this is completely missed in the scheme of things and why certain people succumb to the disease while others survive.
https://en.wikipedia.org/wiki/Factor_V_Leiden
https://www.mayoclinic.org/diseases-conditions/factor-v-leiden/symptoms-causes/syc-20372423
Similarly, I’ve heard a couple times on the radio that people with type O blood are less impacted by CV-19. I haven’t seen any real data to support this, but it would fit with the fact that people with A and B types have a higher risk for clotting.
https://www.heart.org/en/news/2020/01/23/whats-blood-type-got-to-do-with-clot-risk
I don’t know about Factor 5 Leiden, but I do know that deceased covid patients have increased levels of AngII, which is profibrotic (facilitates blood clotting). ACE2 converts AngII to an antifibrotic mediator, but as virus infects ACE2 sites that capability decreases, and AngII increases, increasing thrombosis risk.
Rud,
1. How about daily low dose aspirin as a prophylaxis against clots due to c-19..
2. Any difference in outcomes for c-19 if using ace1 vs ace2 inhibitors or arb’s or beta blockers.
There is a clinical trial for a drug that loosens mucus.
Bromelain IIRC.
Not available in the US, but we do have guaifenesin, available OTC.
The idea is to prevent the initial stages of pneumonia where failure to breathe deeply over a few days causes pneumonia to initiate and then it progresses.
It is well known that broken ribs can cause pneumonia, or being in bed 24/7 for an extended period. Even if someone has broken legs, very good idea to get up and walk at least a little bit every day.
Would it not be amazing if people that treat cold symptoms by taking remedies available OTC are what prevents serious illness in some people?
Personally, I never buy things like Nyquil.
I get pills of each ingredient, generic in large bottle. Cheap as dirt.
Antihistamines (drowsy and nondrowsy ones), nasal decongestants, mucus relief, cough suppressant, pain relief.
Only treat what symptoms I have as needed.
But it takes a little knowledge.
Not a lot, just a little.
The west is self immolating. I think the USA will survive as republican states will open up despite the media ands Trump who will be losing his base support unless he changes the whole CDC real quick. The democratic states can self immolate if they want NY with a lot of cases and California with absolutely virtually none is applying the same rules will also suffer much more and the democrats may dissappera as a party because of this. I am very worried about Australia my country (although I left years ago) as they think a victim number 78 a 96 years old woman with preconditions died from coronavirus is worth closing down the whole country and economy for another month. Australia will lose all its markets to China on which it had been dependent. BTW I dont think the Chinese pushed this virus I believe it is just a normal flu corona virus that exists everywhere everybody will get it or has it and it does not do anything to anybody but if it it infects very old people like NORMAL FLU viruses that are already dying in nursing homes yes it will kill them. People seem to be forgetting that old people die its normal we have no right to kill young people our daughters and children because of incredible stupid economic lockdown policies. Sweden and Brazil seem to be the onl;y smart people for christ sake 170000 old people die per DAY WAKE UP to date this virus has not been able to get even close over 5 months!!!
What good has the CDC ever done (not going back to ancient times)?
Except that all cause mortality, measured by weekly deaths, doubled in Spain; doubled in the UK; doubled in New You to; and even rose 20 to 25% in Sweden in recent weeks. We may reasonably infer that the majority of these cases, save Sweden, is because of Covid19 infections. (The NYTimes published these facts, recently.) And thus we do have the worst epidemic and pandemic of this century on our hands. And these costs in numbers of lives will be greater with a do nothing to mitigate policy.
Please provide evidence it’s a pandemic.
And that the lockdowns (plus mass panic) are not the main cause of the increased death rates.
In regards to Trump about possible use of sunlight for virus treatment. Maybe not so outlandish if you want to explore all possibilities. Consider the “Pulse Oximeter” operation. It uses a red light and an infrared light which ‘shines’ through your fingertip to measure the oxygen concentration in your blood. Who-da-thunk that? https://www.howequipmentworks.com/pulse_oximeter/
Mine is powered by 2 (ea) AAA batteries. Someone had the open mind to give it a try! Is there a spectrum of ‘light’ that could kill a virus? If there is could the process be called a disinfectant?
It worked in Star Trek against the giant neuron brain eating creatures from planet Zlorch.
(actually they never said where the neural parasite creatures that they found on planet Deneva came from, just that they were likely from outside the Milky Way.
That is good enough for me!
And heck, even a flashlight will shine right through your whole hand.
Just go into a dark closet and place your hand over one while it is lit.
Very astute observation, EOU!
“It worked in Star Trek against the giant neuron brain eating creatures from planet Zlorch.”
That was good on its own.
Your clarification for exactitude convinces me that the Big Bang Theory is a reality TV show.
Is there a spectrum of ‘light’ that could kill a virus?
There sure is! UV-C works great against viruses, bacteria, fungi, pretty much anything with DNA. I have a UV-C sterilizer box made from a pair of fish tank sterilizers that I use to sterilize my cell phone, car keys, security badge, etc. almost daily.
Unfortunately UV-C will also kill pretty much any other cell in your body so if you try to “disinfect” yourself with UV-C, COVID-19 will quickly become a minor concern.
My finger hasn’t fallen off yet.
I wonder what would happen if a bat infected with COVID-19 was placed outside in direct sunlight for a few hours and then tested for the virus? Simple, quick, and easy experiment. Could the normal lack of sunlight be the reason bats seem to harbor various corona virus’?
In consideration of the effects of such a test/experiment on the bat one should consider the impact on the bat. One result could be that the bat is cured of the virus and gets a suntan. The other is that the bat only gets a suntan.
You want optic fibers into your lungs?
Reread and try to comprehend.
With regards to Trump about possible use of a disinfectant for virus treatment. Maybe not so outlandish if you want to explore all possibilities. Alcohol is claimed to kill the virus on surfaces in a matter of seconds. In a lung infection could a couple of breaths of vaporized alcohol delivered directly to the lungs where the issue is relating to the virus act as a disinfectant. Worse case is the patient may get A DUI if it is done on a drive thru basis!
I only catch a cold or flu once every 5-6 years if that often. I inhale a salt solution thru my nose at the first sign of congestion. Then, as my grandfather would say, grab the whisky and have a little snort or kiss the baby (have a drink directly from the bottle). I can’t ever remember him having a cold or flu. Anyway, the threat of the flue is a good excuse to pull one! Oh yeah …. Vitamin C at about 4000 mg every 3-4 hours for a couple of days.
Judging by the number of times, in recent years alone, that Keith Richards has been found alive in a hotel room, it seems as though pickling has a tremendous preservative effect…but it HAS to be taken internally.
Anecdotally, I understand that the only medicines that Lewis and Clark took with them were some sort of laxative and rum. They lost one man to appendicitis. However, I think they made men tougher in those days — or, they just didn’t survive childhood.
I suppose if you’re really tough a laxative might get rid of appendicitis.
What suggests that surviving childhood was due to anything but luck?
Cross-reactive T-cell memory responses among beta-corona viruses is a leading hypothesis on the “why” of asymptomatic individuals who have viral RNA shedding indications of being infected with SARS-CoV-2, even though they do not have the highly specific antibodies to SARS-CoV-2 proteins.
For those with some immunology background and an understanding the T-cell/MHC nomenclature, then this review from 2017 is a good start:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113894/
A number of the peptide epitopes in the Spike and N viral proteins are known for some of the common human MHC-1 (CD8+) and MHC-II (CD4+) types. This of course is useful to try and get vaccines to induce Tcells specific for those viral peptides. That simply making a CD8 or Cd$ T cell that engages those MHC-peptides is a long ways (immunology speaking) from getting to those T-cells to form a potent, long lived cytoxic T cell memory populations.
The vital issue I have consistently warned about with the latest SARS-CoV-2 vaccine development using patentable mRNA and DNA vaccines to the Spike protein and the N protein is highlighted in that review article:
Specifically, I would note the authors of that above referenced review WARNED (my bold for emphasis):
“These studies demonstrate that T cells play a crucial role in SARS-CoV clearance and elucidate the avenues for vaccine development against other human coronaviruses, including MERS-CoV (Du et al., 2016, Wang et al., 2016a). However, some SARS-CoV vaccines led to the occurrence of Th2-type immunopathology in spite of antibody and protection against infection with SARS-CoV in mice (Tseng et al., 2012). Therefore, the application of a SARS-CoV vaccine in humans should proceed with caution.
This point on immunopathology of Th-2 response to a viral lung pathogen by a vaccine that only induces antibodies is a big warning. Really big. Since COVID-19 is a deep lung respiratory pathogen, the development of a Th-2 response in the lungs and airways will certainly lead to a much worse outcome upon natural virus infection of the individual. Because the lungs and pulmonary airsacs are constantly hit by all sorts of otherwise benign, but foreign “stuff” we breath that is not a pathogenic virus, the lungs and the immune response there have to be very tolerant. But they still have to be able to form potent T-cell responses when a true pathogen is presented.
These mRNA and DNA vaccines being developed I think are **UNlikely** to drive the potent development of a proper long-lived T-cell CTL memory response, IMO. The immunopathology is usually an eosinophilia that exacerbates airway/bronchial restriction and is essentially an allergic-type reaction (similar to asthma) at the same time the lungs and immune system are battling the virus. Really bad juju. This is what happened in the RSV vaccine of the 1960’s given to children. RSV is deep lung viral pathogen (like COVID-19) that is a common childhood virus. Attempts to make a vaccine used a formalin-inactivated RSV that did indeed develope a potent antibody response, but it failed to develop a memory T cell cytotoxic (called a Th-1) response essential to clear the virus-infected cells when the real virus was encountered and infected some children. This resulted in a Th-2 skewed response (insufficient Th-1 T cell cytotoxic response).
***Children died because of this RSV vaccine that was supposed to save them.***
The RSV vaccine was an inactivated virus. That is it was thought very safe because it couldn’t replicate once taken into cells and use its RNA to translate to proteins and give all the anti-virus warning signals (pattern recognition sensors for various forms of viral RNA) for the cell’s internal defenses that primes a T cell response to be cytotoxic to that infected cell. There is very complex and increasingly described innate pattern recognition receptors (PRRs) inside all nucleated cells that triggers these key anti-viral responses (interferon release being one key component) and warning signals that are essential then to drive the downstream and proper priming of cytotoxic (Th1) T cell responses. Without these viral warning signals from the internal PRRs detecting viral RNA, signals that only come from a replicating virus, then the T cell response will either be weak, non-existent, or even tolerizing (really bad).
It is not a coincidence that all the vaccines we give our children to common viral pathogens are Live-but Attenuiated virus vaccines. Measles, mumps, rubella, chicken pox, polio, Hepatiis-B vaccines are all live-attenuated viruses that form the vaccine response that produces both B-cell (antibody makers) and T-cells (“Cytotoxic” means that CD8+ AND CD4+ T-cells recognize viral peptides ofn the surface of infected cells and eliminate those infected cells by direct-contact and pumping them up with potent enzymes that force them to die.)
All those childhood and respiratory virus vaccines mentioned above inject a live virus for each of those pathogens inside the body. That is a virus that can replicate, but attenuated because some of the virus’s abilities to evade the immune system have become deactivated/eliminated from its RNA or DNA coding. But that replicating virus still effectively primes both a potent memory B-cell/antibody response (the memory B-cell response forms highly differentiated population of B-cell clones called plasma cells. Plasma cells go hang-out in bone marrow throughout the skeleton where they then pump-out a steady supply of IgG to the blood stream for years to decades) and the needed T-Cell (Th1) cytotoxic memory cell formation.
The big reason no one wants to make a live, attenuated virus vaccine for SARS-Cov-2 is there is no big money in a vaccine like that. Even though would be the quickest and likely most effective path to putting the COVID-19 out the pandemic business.
Joel
You remarked, “… there is no big money in a vaccine like that,” That seems quite cynical. If a vaccine can be demonstrated that is effective against the current strain(s), then the almost inevitable mutations would require periodic tweaking to maintain the effectiveness. That is a lot like the razor blade marketing model. The bigger problem is whether an effective vaccine can even by created. I think that the effort needs to be encouraged in the way that corporations respond best in a capitalistic society.
You really didn’t get the gist of my argument. All those fancy “new” vaccine attempts with patentable approaches, not one of those modalities is currently an approved vaccine for anything.
All our effective vaccines where the lungs are involved are Live, Attenuated virus vaccines. And SARS-CoV-2 is a deep lung pathogen. The likelihood of inducing a Th2-skewed immune response, rather than the needed Th1-response, with these mRNA and DNA vaccine approaches is high to very high IMO. The authors of the above reference Review article warn exactly of this outcome with a SARS-1 vaccine that do not prime a cytotoxic T-cell response. SARS-2 (SARS-CoV-2) will be no different.
The only reason pharmaceutical and biotech companies are proceeding down those paths is because those modalities are patentable. They are being lured astray by visions of vast fortunes coming their way for a COVID-19 vaccine.
Time is of the Essence. The World Economy is shedding Trillions of dollars of lost economic productivity with each week this goes on.
And everyone is dicking around with mRNA vaccines, DNA- vaccines, virus-like particle vaccines, simply because that is where the *promise* of money is for those companies.
We simply need a mass produced attenuated strain of SARS-CoV-2 virus to prime the Th-1 immune response to form both an antibody response and a Th1- T cell cytotoxic memory response.
Joel
Your remarks sounds like someone who believes in “Good enough for government work!” I have no trouble with Big Pharma making drugs that are better than what exist, and making money doing it. That is how capitalism is supposed to work. Making a better mousetrap and charging more for it. I’m glad that I’m not forced to buy a Yugo and can buy a Corvette if I want one. Now, if you don’t want to use a patented drug that comes out, feel free to use HCQ.
All germs can mutate. Why are the other vaccines never updated?
How many flu vaccinations do sailors get?
The US DoD policy is annual flu vaccinations for all active duty, selected reserve, and national guard personnel.
https://www.med.navy.mil/sites/nmcphc/program-and-policy-support/Pages/Influenza.aspx
“Secretaries of the Military Departments.
o Will achieve 90% seasonal influenza vaccination of all military personnel no later than January 15, 2020”
That explains a lot… The Navy mandates unproven drugs, but then President Trump is accused of being anti science just for hoping that hydroxychloroquine might help…
Buffoons Chief Fauci was asleep when these stupid vaccines were promoted?
“How many flu vaccinations do sailors get?”
Are we talking Popeye, or Barnacle Bill?
Re:
How do they arrive at this? What do they measure against?
Somewhere I read that the main test for determining live virus (rt-pcr test) is wrong about 30% of the time.
Yet, apparently one of the steps in the sewage anitbody analysis (being developed at Biobot) makes use of some of the same testing processes. Are the two tests interdependent?
Thanks for the article.
Hervé Seitz (CNRS researcher on micro ARN) says that RT-PCR is too sensitive (as a criticism of Didier Raoult – he is an anti Raoult militant).
His YouTube channel:
https://www.youtube.com/user/HKeyHKey/videos
very interesting article
https://quillette.com/2020/04/23/covid-19-superspreader-events-in-28-countries-critical-patterns-and-lessons/
Indeed, a very interesting article, important for all decision makers.
‘cleanup needed on isle 3’ … Sounds like a presidential briefing. Please do not inject bleach into yourself or others. Although… internal use of ultraviolet light???
EUROMOMO stats have been updated for week 14 and 15:
https://www.euromomo.eu/graphs-and-maps/
Sweden now at 10.91 in week 15. Might be adjusted further up. No decrease from week 14 and week 14 was adjusted upwards as well. Just 7.81 before when I checked.
Week 16 is still delayed cause there is no way Belgium stays so low.
Spain might have a lot of under-reporting of COVID-19 deaths as excess mortality is a lot above Italy which can not be deducted from COVID-19 reported deaths.
Excess mortality has topped flu season 2018 in merely 5 weeks and still counting.
” age 41, had to have his right leg amputated as a result of CoViD-19 induced deep vein thrombosis.”
–
He was put on a ventilator, dialysis and an ECMO (extracorporeal membrane oxygenation) machine,
–
Just to be clear it is rare to amputate a leg for deep vein thrombosis complications.
Usually it is an arterial thrombosis.
In this case the patient had a cannula inserted in a leg artery, probably the right leg femoral artery, which thrombosed.
Only speculation but highly likely not a DVT
Rudd, enjoy your posts. Have you heard of ACE 2 blockers for hypertension as a possible preventative treatment? Would it be worth a try?
Seeing as how the virus wants to attach there as well.
Definitely worth a try. Two approaches that I am aware of: 1) use recombinant human ACE2 as a decoy for virus to attach to rather than ACE2 on cell membrane; not sure if it’s IV or nebulized, and 2) use ARBs or ACE inhibitors to keep inflammatory ACE axis signaling from increasing.
I wonder how the nicotine vapers went in their study or aren’t they telling?
https://www.rt.com/news/486605-french-study-nicotine-resist-coronavirus/
Assuming you’re not vaping THC with vitamin E acetate oil as well-
https://athra.org.au/blog/2019/09/16/scaremongering-about-vaping-will-cost-australian-lives/
With a rush on ‘nicotine substitutes’ naturally the French Govt had to jump on it although they don’t mention restricting nicotine ejuice-
https://www.msn.com/en-us/health/health-news/france-restricts-sales-of-nicotine-substitutes-after-coronavirus-study/ar-BB139qyJ
Post modern séance is as much about the things you don’t investigate as those that every true ologist must.
Where is the risk in using a killed c-19 vaccine for the elderly TODAY?
We already have the technology and the risk from a killed vaccine far outweighs the risk for the susceptible population.
A live vaccine or genetically engineered vaccine I agree needs safety testing. But the worst you are likely to see with a killed vaccine is an allergic reaction, which are routine in any vaccine.
Sure a killed vaccine is not going to yield perfect immunity, but for the vast majority of the elderly it could make the difference between a mild illness and death.
Personally I’d rather have a good solution today rather than a perfect solution long after I needed it.
There is no “killed vaccine”, therefore no risk.
What about the flu vaccine that makes you more likely to get Kung Flu?
Or this one?
https://childrenshealthdefense.org/news/pertussis-vaccine-failure-not-failure-to-vaccinate/
Breaking …
Ivermectin is looking more and more like it could be a silver-bullet drug that emerges to bail us out of our difficulties. The news regarding same is getting more and more interesting.
https://mainichi.jp/english/articles/20200425/p2a/00m/0na/007000c
Excerpt: According to the team, the death rate of coronavirus patients declined to about one-sixth, compared to the rate of death in those who did not use the medication.