Posts by THHuxleynew

    Then there is cross-over immunity, where there are anti-bodies from another coronavirus infection that protect against COVID,

    Put it all together, and it may be that 80% are immune like Wyttenbaxh says. At this stage though, it is all guessing.



    The problem is cross-over effects cut both ways. The near matches can prevent normal antibodies forming but provide no protection. So we don't know this effect.


    There has been enough evidence to show the T-cell effect - and we know COVID is unusual in stimulating T-cells - they seem much more important in successfully fighting it than for other diseases.


    The Diamond Princess gives us a limit (for that population) on immunity: 3000 people, 712 cases => At MOST 77% immune. that assumes that everyone on the ship was exposed enough to catch the virus - unlikely.


    In addition, when we talk about immunity, we probably mean partial immunity. A small dose infection might be fought off, when a larger dose would not be so.


    Another reason to think immunity is not so very high is just the high R0 numbers. If only 20% of contacts can catch it the high reproduction rate it has ben showing seems unlikely?


    A lot of uncertainty because previous exposure immunity could be very variable across populations. The best prophylatic probably is a few CV colds - difficult though to get them right.


    THH

    I am not trying to be provocative here.... I sincerely want your personal opinion which you have not given. If you do not want to give it fine, simply please state it.


    So you are advocating "doing nothing" as far as prophylactic treatment because there have been no RCT's? A straight forward question.


    There have been RCTs - with marginal results. Prophylaxis is the most difficult thing to judge because:


    Any adverse effects will hit the 95% of people who never get covid symptoms

    It maybe must be continued for a long period, so side effects over time can be an issue

    Proving that anything works as prophylaxis is difficult because you need a large number of patients on the trial to get statistically significant results.


    I would advocate using prophylaxis if any drugs seemed to benefit me on a risk/reward basis. Obviously that is a lower bar if I reckon I am at high risk of catching COVID.


    I'd also take anything that is so GRAS the risk of side effects is minimal, where there is a plausible possibility it might help.


    Zinc, Vit D - sure, take them in relatively low doses (high doses they both have nasty side effects). I am doing this.


    Quercetin - a bit marginal because it does have a few side effects but does not seem troublesome and any way it present in a lot of food. I'd be careful about possible ODing on it - given it has side effects and you might have a large amount in food.


    HCQ, Ivermectin - they are both active substances with real side effects. HCQ in particular has a long time it stays in the body, and it is active in the immune system. So if as seems likely from current RCT evidence it makes severe COVID a bit worse, it would need to be a good prophylactic. I'd very much like to see a test of this - there are some ongoing RCTs so let us hope we get this. The small RCT that has some evidence has to be reinterpreted so much to provide this that I don't trust it, but do see it as cause for hope. In that case if you watch out for sight loss and heart problems, you could take HCQ on the possibility it is an effective anti-viral. I would not, given the medical evidence against this. Ivermectin - I just don't have much evidence on this. I might take it if I had researched side effects carefully and they seemed to me irrelevant.

    A secondary analysis has found several inconsistencies in the data [3],

    and found evidence of excess mortaliy within the first few days that could be due to overdose.[1] twitter.com/JamesTodaroMD/status/1272661099985481733


    I'd be interested in this if the secondary analysis were written up as a proper preprint, rather than a political (HCQ is political in US and France) interview?


    Twitter is not a reliable source of info.

    Most people (>80%) are immune


    This is a fascinating topic.


    We have:


    1. symptomatic (and antibody positive)

    2. asymptomatic (and antibody positive)

    3. symptomatic (and antibody negative)

    4. asymptomatic (and antibody negative)


    3,4 are where T-cell response (possibly from past infections) fights off the virus.


    My guess is that by "immune" you mean 4 and possibly 3. T-cell response to the infection fights it off when relatively mild, before antibody production starts.


    https://www.nature.com/articles/s41586-020-2550-z


    Notably, we detected SARS-CoV-2-specific IFNγ responses in 19 out of 37 unexposed donors (Fig. 4a, b). The cumulative proportion of all studied individuals who responded to peptides covering the N protein and the ORF1-encoded...


    That looks like 50% have some T-cell immunity, not as you say 80%? it will vary with population, so maybe some places have 80%? Give details, or admit to Wyttenfacting.


    Also worth noting somone who has done the correct calculation for herd immunity - the immumologists who used the figure for vaccination always annoyed me. More socially active people have more contacts and are also more likely to catch the disease and become immune, so the realistic herd immunity figure is more like 43% from https://www.sciencedaily.com/r…/2020/06/200623111329.htm


    Putting these two things together, you might hope to achieve herd immunity when seropositivity is quite low. Difficult to know how low, since the social contact dependent effect does not apply to the T-cell immunity.


    THH

    Are you joking?? There are databases for LD50 factors never heard of this??


    Have you worked out the pharmokinetics of HCQ, or seen it modelled, like the guy from London Centre of Tropical Diseases (I think) who modelled the dose regime they chose?


    Give me evidence (not Wyttenfact) that the RECOVERY dose was anywhere near LD50 for a one-off dose. And, preferably, think before you type.


    THH

    When will you sue the British doctors that administered deadly HCQ doses that is the base for your FUD you continue to post???


    All active drugs are deadly - to some people.


    Doctors put together clinical trials to work out what works, and what does not.


    The "deadliness" of HCQ in the RECOVERY trial was only apparent after a large number of patients had been treated - not at all evident a priori. And, when it was statistically significant, that arm of the trial was stopped, as the RECOVERY Protocol mandates.

    Please show us a serious correct study that gave this result with HCQ,Zinc plus Doxycycline??


    That exact combination I don't have RCT evidence for. But if you require that - you also lose all the anecdotal positive evidence!


    For example this one does not include Zinc.


    A total of 11% (n=6) patients were transferred to acute care hospitals due to clinical deterioration and 6% (n=3) patients died in the facilities. Naive Indirect Comparison suggests these data were significantly better outcomes than the data reported in MMWR (reported on March 26, 2020) from a long-term care facility in King County, Washington where 57% patients were hospitalized, and 22% patients died. Conclusion: The clinical experience of this case series indicates DOXY-HCQ treatment in high-risk COVID-19 patients is associated with a reduction in clinical recovery, decreased transfer to hospital and decreased mortality were observed after treatment with DOXY-HCQ.


    And my point, well justified by factual evidence and theory - is that Naive Indirect Comparison is a very poor way - effectively useless - to judge a treatment.

    CNN posts plenty of information about people opposed to vaccine, without mentioning conspiracy theories. They have posted plenty of direct statements from such people. They also have unbiased reports and direct quotes about HCQ. You can learn as much about HCQ and the controversy from CNN as from any other mainstream medium that I know of.


    People often confuse left vs right bias, with factual content.


    All media will take a political line left/right/middle, and use this to alter the balance of their reporting. You have to make value judgments when describing things. One person's left (or right) will be another person's "middle of the road" unbiassed.


    Here is a great visual representation. The point is you want near the top, and it does not matter whether left/right/middle. It is true that politics away from the middle tends also to be mixed with less reliable reporting but in principle that need not be so.


    CNN is not too bad, but not great. CNN web a lot better than CNN TV. Fox TV News is quite a lot worse, Fox web news better than TV. Personally I don't like TV as way to get news - it tends to have less info and more emotive content (images and music). I listen to BBC R4 news in preference to BBC 24 hours TV news. That is also why I don't much like the YouTube stuff posted here. If you want the facts instead of the PR go for written reports.


    If you want to be well informed the key thing is the factual content. Is there lots of it? Are the claims made well supported, or completely unsupported. And if you want political information (e.g. what is a fair judgement of Trump's effectiveness as OPUS) you should be reading well informed stuff from the centre, or from both left and right. Personally I can't stand Trump's character and style. In terms of action, I can see how someone with a more right-wing philosophy might like much of what he does. I also note that the "old-style" Republicans see him as dangerous and unsuited in character in the same way I do.


    The conspiracy theory stuff, whether left or right wing, is not factually supported. Otherwise, given its sensationalist content, it would be headline news everywhere - not conspiracy theories!

    Please tell me of one / ANY medicine that has had a comprehensive and widely agreed upon RCT outcome that shows indisputable, positive COVID effect! Please provide what RCT evidence your refer to above that is widely agreed upon and without major error or dispute?


    Your obsession with RCT is simply not well placed here. Why do you not disparage Remedisvir like HCQ? Are you willing to say that it SHOULD DEFINITELY be used because of RCT and those RCT are worthi the paper they are written on?


    I will take front line worker support, HUGE observational evidence, a significant number of other countries formal approval, a seemingly reasonable theory of why it works, availability over DOING NOTHING as HCQ is not dangerous if handled properly.

    It was prescribed over 5,600,000 times in 2017 alone! Yes, that is 5 million plus! Yet it is deadly?


    Everyone wants to have a treatment. throughout history, doctors have given treatments that actually harm patients, with doctors and patients convinced this is helping. I think the main difference in attitude between most on this board (and me, initially) and the medical establishment is that medics now - the research ones who look back at effectiveness - have had their fingers burnt a lot and are very cautious about letting people push treatments even for emergency use as now.


    COVID is not like a broken leg: the same for everyone, you can see how bad it is, you can measure time till it is mended and observe differences easily.


    The variability between patients is enormous. Most recover quickly. Some don't. A few die. The exact percentages here (around 0.8% die of those infected) vary a lot, regardless of treatment, with external factors: age, sex, race, even the severity of the initila dose.


    Front line workers are not in any position to work out whether a drug works. Researchers, reviewing hospital records, can do retrospective studies using complex stats, trying to match patients. As we have seen, these are highly unreliable. They are especially bad for technical reasons in the case of COVID, because the relationship between age and severity is very strong and highly nonlinear. You need a lot of patients, and the right stats, just to get rid of unintended correlations with age. That is why RCT results are even more necessary to work out what works for COVID than for other things.


    And that is also why working out what is good treatment is so difficult.


    Mostly, in this situation, doctors will be willing to try anything, in a trial, in the hope it might work. HCQ has been tested 10X more than anything else, with (now) lots of data from RCTs showing that it does not help, and on balance slightly harms, hospitalised patients.


    Remdesivir has very little data (that I've seen). I agree it was pushed through as "approved" on minimal evidence (like HCQ in France). Maybe that is big pharma influence. Either we will end up with better evidence, or it should get taken of the approved list fairly soon. The difference with HCQ is that we do not have lots of high quality negative data on it.


    THH


    Shane - you are badly wrong.


    The RCT evidence on use of HCQ in hospitalised (=> not early stage) patients is that it harms, slightly. Certainly no evidence it does good.


    You seem to put non-RCT evidence which is all over the place and we know can easily be pushed eitehr way by confounding factors above the plentifyl RCT evidence. Why?


    I can see uncertainty in whether HCQ is good post-exposure pre-symptomatic prophylaxis - or even good "take it all the time" prophylaxis. I'd leave it to doctors. However for severely ill patients the evidence is it harms. Letting doctors to this based on a poor undertanding of the data is just killing more people.


    THH

    https://www.medrxiv.org/conten…101/2020.08.04.20167205v2


    Telmisartan (cheap, for those who reckon any expensive drug with positive results is part of a medical-pharma conspiracy)


    Appears to reduce time to discharge over standard treatment. Small randomised trial, but very statistically significant result.


    This study shows 50% mortality reduction - but at p=0.41 that has no significance.


    These results are the ones we badly need more and larger tests on - what dose, who does it help, how do different drugs combine.


    THH

    The US case rate has been nicely falling the last week or two, encouraging news. However detailed data shows the number of tests going down overall, and particularly in the hotspots the positive test / overall test ratio is going up. This nearly always indicates more positive people who never get tested.


    So it is not that we know the US real infection rate is going up or down. We just don't know what it is doing.


    https://www.express.co.uk/news…y-data-cases-texas-latest

    Lou & W


    Your point is the RECOVERY trial used high front-loaded concentrations of HCQ. True, lower doses would have less bad effect.


    the point is that they used a high dose exactly because this was needed to get plasma concentrations up quickly to a level where a pharmacologically active effect was posisble. So you could reasonably critique all the other hospital studies as giving people HCQ TOO LATE.


    Since what doctors most need is treatment, not prophylaxis, this is not an argument against RECOVERY. The dose chosen was not toxic in healthy people.


    You can always choose untested combinations of parameters where your favourite drug will work. I'm sympathetic to that. I'm not sympathetic to you arguing here:


    (1) HCQ needs to be given early


    and


    (2) The one study which takes that (obvious) fact seriously and gives a high front-loaded HCQ dose, to allow it to be effective earlier given it accumulates slowly over time, is then called by you "designed to fail".


    THH


    Re HCQ - NHS here is no way in the pocket of big Pharma - and has a similar view of HCQ for patients in hospital with COVID symptoms. It does harm.


    I'm sure that money does influence medical decisions, at the margin. It definitely affects which drugs get funding for tests. If in the US you reckon regulation is so corrupt that it does so in major ways I'm sorry for the US.


    You'd better choose a different example that some crackpot doctor claiming regulation designed to protect severe COVID patients being killed from his giving them unhelpful drugs.


    Let me say again: HCQ is pretty safe normally. It interferes with the immune system and appears dangerous (though we can't yet be sure how much) for those in hospital with COVID.


    THH

    In the pipeline is my fave science blog for following COVID matters. Some recent articles.



    Monoclonal antibodies look good as treatment - but a long way still to go:


    https://blogs.sciencemag.org/p…body-cocktail-in-primates


    Novavax looks good so far as a vaccine candidate:


    https://blogs.sciencemag.org/p…vaccine-data-from-novavax


    Biopharma stock cults (investors beware!)


    https://blogs.sciencemag.org/p…cults-and-the-coronavirus


    The russian vaccine announcement was a pitiful PR stunt:


    https://blogs.sciencemag.org/p…08/11/the-russian-vaccine


    The problem I have with this is that it is a social science response to a scientific problem.


    HCQ, ivermectin, etc - they work or they don't. There are definite answers which we will at some point know -it is just we have partial info at the moment.


    I agree - the info is partial - the establishment may be wrong.


    I disagree - therefore we should do the opposite of what the establishment says because they are left wing influenced and, hey, we know that is wrong.


    THH

    Deaths due to COVID misinformation


    https://www.bbc.co.uk/news/world-53755067


    As vaccines emerge, there is the further threat that anti-vaccine campaigners will use the platform provided by social media to persuade people not to protect themselves.

    Despite social media companies removing or labelling misleading information about vaccines, recent polling in the United States showed that 28% of Americans believe that Bill Gates wants to use vaccines to implant microchips in people.

    The achievement of an effective coronavirus vaccine could be completely undermined by misinformation, doctors told the BBC's anti-disinformation team.


    Bill Gates wants to use vaccines to implant microchips in people?


    QAnon takes over Congress?


    How about campaigning for truth and against twisted conspiracy theories? It may not be trendy in the weird 2020s, but it sure is necessary!


    THH

    As said it is outrageous to ask for a RCT


    Well lots of people are doing RCTs, so lots of people obviously disagree with you.


    Or do you prefer the Oxford way,


    Yes, i prefer multi-arm interventional randomised trials. Everyone gets a possibly excellent treatment, you see which work best, over time you drop the least good ones and add new ones.

    Has everyone been following Leronlimab? This treatment really works and results are proving it. This just announced today.

    https://finance.yahoo.com/news…ficant-top-131500914.html


    It looks pretty good, though as always I'd like to see the test details and how much cherry picking etc. I guess we find out - if the regulators like it enough it will get allowed quickly.


    It does seem pretty likely we will have good treatments for all stages of COVID eventually, and should be able to stop it going to severe illness in nearly all cases. Just it takes a long time to work out what to give in what dose when.


    THH