Covid-19 News

AstraZeneca vaccine transverse myelitis

... "In 1922 and 1923, physicians in England and Holland became cognizant of a nervous disorder that occurs as a rare complication or sequel of jennerian prophylaxis. To this condition has been given the name postvaccinal encephalitis. Since its recognition, ninetythree cases have come to light in England, 124 cases have been observed in Holland, and a few cases have been reported by workers in Poland, France, Austria, Switzerland, Czechoslovakia and America. The onset of the encephalitis, which occurs in the maximal number of cases on the eleventh day after vaccination, is acute, and the course of the disease is rapid."

Quote from Lou Pagnucco

Small, but statistically significant, study indicates HCQ + vitamin D is effective

in hospitalized later stage Covid infection.

Actually it does not quite do that. The devil as always lies in the detail.

It shows, with high statistical significance, that HCQ + vitamin D is more effective than HCQ on its own.

For example. this comparative result can hold whether HCQ is effective, or harmful, or has no overall effect.

There is also the possibility that as a combination, due to interactions, HCQ + calcifediol is more of less effective than the additive sum of the two individual effects.

Taking it simply, it says nothing about HCQ, but finds that calcifediol is effective.

People are paying not much attention because of the lack of randomised (or mendelian randomised) studies showing any benefit from Vitamin D, and the reality that non-randomized positive studies can easily show positive results because of all the bad things that Vitamin D correlates with, and the difficulty in controlling properly for everything.

Still, this one trial is carefully done, randomized, not double-blind but carefully masked to prevent doctors in charge of patients knowing which group they are, and should be taken seriously. The special case of COVID is different from the general case because Vitamin D (just like HCQ) has known effects on the immune system. As with HCQ working out what those are, and whether they end up positive or negative in COVID patients, can only be decided experimentally.

THH

Quote from THHuxleynew

se of COVID is different from the general case because Vitamin D (just like HCQ) has known effects on the immune system. As with HCQ working out what those are, and whether they end up positive or negative in COVID patients, can only be decided experimentally.

" can only be decided experimentally."

I disagree to some extent with this. Observational evidence CAN be used to determine if an agent is effective or not! It does NOT have to have a RCT or "experiment" specifically. It certainly does not hurt to have such and I am not against it, but lacking such investigations, experiment is not absolute! You diminish observational evidence too much!

Take scurvy for example....

"In 1579, the Spanish friar and physician Agustin Farfán published a book in which he recommended oranges and lemons for scurvy, a remedy that was already known in the Spanish Navy.^[39]

In 1593, Admiral Sir Richard Hawkins advocated drinking orange and lemon juice as a means of preventing scurvy.^[40]

In 1614, John Woodall, Surgeon General of the East India Company, published The Surgion's Mate as a handbook for apprentice surgeons aboard the company's ships. He repeated the experience of mariners that the cure for scurvy was fresh food or, if not available, oranges, lemons, limes, and tamarinds.^[41] "

This was long before the "official" cause and cure of scurvy was found and published! No experiment nor RCT was done here.

HOWEVER..... note this very interesting outcome ....

"He was, however, unable to explain the reason why, and his assertion had no impact on the opinions of the influential physicians who ran the medical establishment that scurvy was a digestive complaint."

https://en.wikipedia.org/wiki/Scurvy

So...... A working cure that was being used successfully by many (without experiment or RCT) and then was PROVEN exceptionally effective and safe several years later was "pooh poohed" and ignored by the "influential physicians who ran the medical establishment" ..........!!!!

How many thousands of lives could have been saved?????????

Hmmmm.... sound familiar?

"Sigh..... yes, we are MUCH more learned and intelligent than those "influential physicians" were back then. Men of Science are not capable of making those mistakes today as they all know better! We cannot trust any observational evidence and should ignore it as it is not REAL science!"

Not a great analogy, unless 99.5% of scurvy victims recovered without intervention.

Quote from THHuxleynew

Actually it does not quite do that. The devil as always lies in the detail.

It shows, with high statistical significance, that HCQ + vitamin D is more effective than HCQ on its own.

Anyone reading the paper easily sees that several (less plausible) hypotheses are possible.

These were patients fairly far along in the disease, and HCQ alone probably would not help,

but it appears that HCQ is a standard protocol for this medical group - could it be that they

really believe it's a placebo? Certainly it is possible that Vit-D is solely responsible (but, I would

bet against it)- easily checked since CRTs are in process. Synergy seems more probable.

Also, since you thought the Recovery study was legitimate despite mega-dosing seriously infected

patients with HCQ, you may want to do a web search on recent papers on the prevalence of

Covid liver injury - which, likely exacerbated the toxicity.

Other subjects --

Common cold combats influenza

- whether colds combat Covid is being studied

https://medicalxpress.com/news…ld-combats-influenza.html

Interference between rhinovirus and influenza A virus:

a clinical data analysis and experimental infection study

https://www.thelancet.com/pdfs…S2666-5247(20)30114-2.pdf

COVID-19 Immunity Short-Lived For Those Who Are Asymptomatic Or Had Mild Symptoms.

Doubts Raised About Ability Of Vaccines To Really Work.

https://www.thailandmedical.ne…f-vaccines-to-really-work

The dichotomous and incomplete adaptive immunity in COVID-19

https://www.medrxiv.org/conten…09.05.20187435v1.full.pdf

Quote from Bob#2

I disagree to some extent with this. Observational evidence CAN be used to determine if an agent is effective or not! It does NOT have to have a RCT or "experiment" specifically. It certainly does not hurt to have such and I am not against it, but lacking such investigations, experiment is not absolute! You diminish observational evidence too much!

Bob - you misunderstand me. Experimentally includes observational evidence.

I do not dismiss observational evidence on COVID treatment - it is just that the specific circumstances of an ever-changing pandemic with outcomes that vary and have only 1% death rate anyway make it very difficult to separate effects. Whereas with scurvy the correlation was pretty well 100%, in both dirctions. Citrus fruit <==> no scurvy, no citrust fruit <==> scurvy.

I don't think you can evaluate observational evidence without looking at all the details - and for that you need a careful scientific meta-study - since you have to compare experiences of many different "on the ground" physicians across different treatments. Having done that, you still have possibly conflating factors (e.g. a country with median age 21 will have only 6% the mortality of one with median age 45. That is an enormous difference, just from different demographics. So, for example, Zelencko's wonderful results are explained by the fact that his patients were mostly from an Orthodox Jewish settlement (Kiryas Joel) with a median age of 13.7 years !!!!!.

I don't blame Zelencko for not doing the proper analysis and realising this: it is no way his job. I blame him for hubris - asserting that he is right over everyone else. And I blame a few other doctors, who should know better, if they take his results without a careful demographic analysis. After all with COVID age is the very first thing you look at because it has such an unusually strong effect on mortality.

To get fair information from observational evidence you not only need to control very accurately for age (not just with approximate age bands, as many do0 but for many other factors. the age dependence is very strong and exponential so you need an logistic regresion, not a linear one.

One reason i like the little Vit D RCT, even though it as masked, not double blind, is because they used a logistic regression (appropriate to this problem - with an exponential risk function) rather than a linear one.

So: sure. Take into account all these factors and then see what the observational analysis tells you - if anything. But how do you know you have done it right, and identified all possible conflating factors? Undoubtedly some studies do this better than others. No guarantee that any do it well enough.

Whereas with RCTs the results are known valid, and their limitations, from statistical errors due to small size, are also known. (And yes, if they use linear regression models to analyse results taking into account random differences between groups, without any of the techniques that deal with nonlinear relationships, that aspect of the analysis will be wrong). Luckily raw RCT results with no such analysis can still determine obvious effects.

This is not about qualifications. It is about whether those doing the analysis have taken into account the known issues. It is difficult for a non-expert to know what is important and why. E.g. logistic regression vs linear regression. Why? Which is best/. Well, I've educated myself. Specifically for COVID - not as a learnt in a classroom mantra (where linear regression often works pretty well). and I'm happy to explain this to others here, or to link people discussing the issues (though maybe not specifically for COVID).

Don't take my word for it. Look at sober analysis from real experts, e.g. CEBM -UK Oxford - non-political

https://www.cebm.net/covid-19/…-clinical-trials-tell-us/

[reviewing various observational trials, one of them]

This is the best study so far published. The authors took steps to reduce the risk of time-dependent bias and to rule out confounding factors. They emulated randomization and balanced the differences in baseline variables between the treatment groups using a prespecified non-parsimonious multivariable logistic regression model. They also recorded adverse events and in particular took care to measure the QT interval. However, there were limitations: for example, unmeasured confounders may have biased the results and four potentially important prognostic variables could not be balanced in the model. The authors therefore urged caution in the interpretation of the results, especially for overall mortality, with only a few events observed and a very wide confidence interval.

That was an early analysis - since then there has been a good deal of negative data coming in. it certainly does not rule out prophylactic usage - but it is very difficult to get positive or negative evidence for that, and the safety would have to be very high because it would be given to many many people who never needed it. If your argument is "we can't be sure HCQ does not work": sure, I agree. That would be equally true of about 20 untested promising drugs - for example calcifediol. Some of those have less "it does not seem clearly useful" evidence than HCQ, and more promising positive evidence. Some of them are safer than HCQ.

THH

Quote from Lou Pagnucco

Also, since you thought the Recovery study was legitimate despite mega-dosing seriously infected

patients with HCQ,

Are people really still trying to push this tired old red herring?

Lou, are you (and others) incapable of understanding that HCQ has an exceptionally long elimination half-life, and that the levels that build up in chronic users (arthritis & lupus patients) dwarf anything given in the recovery trial?

Perhaps the problem is that pharmacokinetics isn’t exactly a popular topic on youtube?

https://theprint.in/health/vit…panish-study-says/498904/

I agree with this Indian doctor who says that the Vit D (well, calfediol) is no way definitive:

https://theprint.in/health/vit…panish-study-says/498904/

Satyajit Rath, a scientist at Indian Institute of Science Education and Research (IISER) in Pune, said while the study is interesting, the results are not definitive.

“It is an extremely small group of patients. It does not identify the degree of severity of Covid-19 in the patients at admission, and does not provide any details of their clinical progress other than ICU admission and death,” Rath told ThePrint.

He also noted that the study did not specify the co-morbidities that the trial patients were suffering from but instead treated all of them as having an equal risk factor, which was not the case. For instance, an obese patient is more likely to succumb to the infection.

The study also does not identify what comorbidities, if any, the patients admitted to the ICU had, Rath pointed out.

“In such a small group, the small differences between the two groups could be enough to skew the results,” he said.

S.P Kalantri, Director-Pro

But like others here I am optimistic and this result is enough for me to take as high a level of Vit D as is known safe prophylatically, at least until/unless negative evidence comes in. Let us hope this is real: it could be because of the bradykinin hypothesis.

Quote from Zeus46

pharmacokinetics isn’t exactly a popular topic

But it was a hot topic for the RECOVERY trial guys, who got "best effort calculations" from a pharmacokinetics specialist of what would be the highest initial loading dose that kept levels safe.

It should not surprise me that this careful action to try to give HCQ the best possible chance is interpreted by many ignorant of them as a criminal attempt to kill patients and discredit a life-saving drug.

https://www.bmj.com/content/370/bmj.m2670/rapid-responses

Martin Landray, has defended the dosage used. He told the BMJ, that the dose was arrived at using “detailed pharmacokinetic models” developed by Nick White and his team “to rapidly achieve drug levels that might be high enough to kill the virus but not so high as to trigger toxicity”.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417172/

Quote from Bob#2

I disagree to some extent with this. Observational evidence CAN be used to determine if an agent is effective or not! It does NOT have to have a RCT or "experiment" specifically.

I'm pretty sure Socrates did know about the RCT of hemlock.

Quote from Zeus46

Not a great analogy, unless 99.5% of scurvy victims recovered without intervention.

Ahoi captain - the sailors would have loved you. Water instead of lemons...

Quote from Lou Pagnucco

Also, since you thought the Recovery study was legitimate despite mega-dosing seriously infected

patients with HCQ,

Do not try to teach the dilettantes ...

A decent sober discussion of the bradykinin hypothesis - written rather than video PR - linking the source paper:

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

To be honest, I’m worried that this proposal is almost too neat and form-fitting; rarely do you get something that falls together this well. It’s also quite possible that you could come up with a reasonable set of literature references and previous reports that cast many of these connections into doubt – the medical literature is large, and you can find support for a lot of things if you’re putting together a brief for the prosecution. But overall, I find this work pretty plausible.

To that point, a very good feature of this work is that it immediately suggests several interventions with FDA-approved drugs. Not all of these are actionable (for example, androgenic steroids decrease bradykinin production, but do a hell of a lot of other things besides!) But icatibant (brand name Firazyr) is an antagonist of bradykinin B2 receptors, and ecallantide (brand name Kalbitor) is an inhibitor of kallikrein, a key enzyme in bradykinin production. Both of those would seem to be directly targeting the proposed mechanisms. Hymecromone is a small molecule that’s known to inhibit the synthesis of hyaluronic acid. And thymosin beta-4 is a protein that could tie into the connection between bradykinin activity and coagulopathies; a version of this protein has been in human trials as Timbetasin. As mentioned above, vitamin D supplementation might also be beneficial – its receptor has connections with vascular permeability and with the renin/angiotensin system, and its deficiency has already been noted as a rsk factor in the current pandemic. I agree with the authors that controlled trials of all of these therapies would seem very worthwhile – hymecromone is a particular standout from what I can see, being generic and inexpensive, and if it can directly improve lung function in severe coronavirus patients, that would be a real accomplishment. Its weak point is that it has caused diarrhea as a side effect with even further potassium lowering, so you might want to give that with potassium supplementation (?) I am most definitely not a clinician, though, so I’ll leave my suggestions out of it.

4 drugs to try - and Vit D - all better (because plausible and no negative evidence yet) than HCQ. These are attacking the stage of the disease that matters, its transition from symptomatic mild to severe.

Who, with me, is going to cheer lead for the cheap, generic, Vitamin D and hymecromone?

THH

Quote from THHuxleynew

Bob - you misunderstand me. Experimentally includes observational evidence.

I do not dismiss observational evidence on COVID treatment - it is just that the specific circumstances of an ever-changing pandemic with outcomes that vary and have only 1% death rate anyway make it very difficult to separate effects. Whereas with scurvy the correlation was pretty well 100%, in both dirctions. Citrus fruit <==> no scurvy, no citrust fruit <==> scurvy.

There have been many medical breakthroughs that were confirmed without blind tests. Penicillin is a famous example. The effects were so clear -- so dramatic -- there was no need for blind tests. In the treatment of COVID-19, it was quickly observed that ventilators were not very effective. Only about 20% of patients put on ventilators survived. So doctors and nurses made every effort to find alternative ways to keep the patient's lungs clear. They soon found that putting patients on their stomachs was more effective than you might think. (Than you might think based on other lung diseases.) This quickly became a standard therapy. There was no need for blind tests.

This is not to say that blind tests are a bad idea. When the therapy or drug has only a minor effect, the only way to detect it may be with blind tests.

Blind tests can be very difficult to do when the patients are very sick and many different therapies and techniques are being used at the same time. Boris Johnson and others in intensive care noted that a nurse was there by his side 24 hours a day. One nurse said his job was to keep an eye on things and to adjust the equipment, and that it required constant small adjustments. I do not know what equipment that was -- perhaps an IV? Anyway, the doses of medicine and other parameters are constantly watched and adjusted as needed to keep the patient alive. The doctors do not understand the disease in depth yet, the way they understand diseases that have been around for thousands of years, but there are commonalities and of course, pneumonia is pneumonia, no matter what causes it, so they have some effective ways to save many patients. For that matter, a doctor in ancient Greece or Japan would probably have been able to help. Some of the therapies described by Hippocrates are very similar to modern ones.

Doctors and nurses can help even though there is no vaccine. That also tells you that if the hospitals are overwhelmed, and there are not enough doctors and nurses, many more people will die. This happened in Italy and in some districts in the U.S., in Florida and Texas. The case mortality rate will go much higher. Unfortunately, because there is so much political opposition to wearing masks and social distancing in the U.S., the number of cases may increase this winter, up to levels that will overwhelm some hospitals again. Projections show that with increased use of masks and social distancing, the total number of deaths by January 2021 may be ~288,000. With today's level of mask use, it will be ~410,000. With mandates easing, it will be 410,000. In short, 122,000 people will probably die because many Americans are irrational, ignorant idiots opposed to science.

https://covid19.healthdata.org…ew=total-deaths&tab=trend

Here is a cartoon opposed to a Republican governor Laura Kelly of Kansas, who ordered mandatory masks. The cartoonist compares a mandatory mask rule to being forced into cattle cars and taken to a Nazi concentration camp. This is an extreme example of the opposition, but there are many less extreme versions, such as recent rallies by Republican candidates in Georgia and Trump rallies in which few people wore masks and there was no social distancing.

Warning once more:

4 care homes in Switzerland heavily infected each with > 30 persons with at least half being staff. In one case 7 deaths so far!

There are vulnerables, that did survive the first wave due to a consequent lock-down. Younger people do not often show symptoms- so the staff is critical.

Care homes should have medicaments ready and hopefully they soon get the new Roche (or similar) quick blood test to monitor the staff on a regular basis.

Quote from Wyttenbach

Ahoi captain - the sailors would have loved you. Water instead of lemons...

Amusing, but missing the point, as usual.

Quote from Wyttenbach

Younger people do not often show symptoms

I do not know if they "often" do not show symptoms. I do not know the statistics for that. The symptoms are sometimes mild compared to older people, but they know they are sick. Two of my nephews and nieces got the disease. They knew quite well they had it! They were miserable. Fortunately, so far their parents did not get it. They are probably in the clear for now.

Many young people have died, of course. Far more than die from things like seasonal influenza. Many other young people have suffered long-term damage such as damage to the heart, strokes, and amputations. Many thousands more have not been able to recover from the disease after weeks or months. They still cannot breathe, or climb stairs, and they have many other intermittent problems. Some long-term effects are described here:

https://www.nytimes.com/reuter…us-long-fear-feature.html

Quote from THHuxleynew

https://theprint.in/health/vit…panish-study-says/498904/

I agree with this Indian doctor who says that the Vit D (well, calfediol) is no way definitive:

https://theprint.in/health/vit…panish-study-says/498904/

Satyajit Rath, a scientist at Indian Institute of Science Education and Research (IISER) in Pune, said while the study is interesting, the results are not definitive.

“It is an extremely small group of patients. It does not identify the degree of severity of Covid-19 in the patients at admission, and does not provide any details of their clinical progress other than ICU admission and death,” Rath told ThePrint.

He also noted that the study did not specify the co-morbidities that the trial patients were suffering from but instead treated all of them as having an equal risk factor, which was not the case. For instance, an obese patient is more likely to succumb to the infection.

The study also does not identify what comorbidities, if any, the patients admitted to the ICU had, Rath pointed out.

“In such a small group, the small differences between the two groups could be enough to skew the results,” he said.

S.P Kalantri, Director-Pro

But like others here I am optimistic and this result is enough for me to take as high a level of Vit D as is known safe prophylatically, at least until/unless negative evidence comes in. Let us hope this is real: it could be because of the bradykinin hypothesis.

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T you might want to read this: Vitamin D for treatment and prevention of infectious deseases:: A symtematic review of randomized controlled trials

http://www.ncbi.nim.gov/pic/articles/PMC2855046/

Quote from THHuxleynew

4 drugs to try - and Vit D - all better (because plausible and no negative evidence yet) than HCQ. These are attacking the stage of the disease that matters, its transition from symptomatic mild to severe.

Who, with me, is going to cheer lead for the cheap, generic, Vitamin D and hymecromone?

THH

I have been taking Vit. D (along with Quercetin and Zinc) for quite a while at least 2 months. Hopefully it already has provided useful prophylactic protection or perhaps made symptoms so minor I was asymptomatic. (An unfortunate issue though, not knowing if one has it or was contagious. One cannot track or trace!)

So I will cheer anything that is safe and works. If not proven to work via RCT, then at least as stated before, has a theoretical basis, is supported by significant observatory evidence from a wide base of medical practitioners.

I will have to investigate hymecromone as it is new to me as of your posting. Thanks!

I just hope that the number of people who contracted Covid or may have had major negative symptoms did not do so because they did not take Vit. D earlier... waiting for such a report!

From Sky News Australia - The jury is in on Hydroxychloroquine – ‘it saves lives’

- examines the political/financial motives driving the HCQ ban

Quote from Bob#2

I will have to investigate hymecromone as it is new to me as of your posting.

Whoops - sorry. I did not mean anyone to do that:

hymecromone not a commonly used drug - it is one of many that should be trialled as possibly treating the often fatal "cytokine storm" that makes COVID so deadly. Not for home dosing, and of no use as a prophylactic, because no reason to think it will stop you catching COVID. if you needed it you would be in hospital but the doctors there would have no idea without a lot of research what would be a suitable dose of it for a (very) experimental trial - and would not want to do it as a one-off.

But Vit D is worth best efforts to try given total evidence so far - and that would be a home Vit D test and adjusting supplement level on basis of that (but it takes some time since Vit D is long lasting and you would need to wait a few months before knowing what the effect of supplementation would be). And take medical advice on what is an appropriate safe level - Vitamin D overdose causes harm.

Home mail order Vit D tests cost £27 in UK, probably around $30 in US?

THH