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HELP THE NHS ~ I've let my adjoining empty house (fully furnished) to four NHS nurses free of charge during this National Emergency. We have a very large General Hospital at the top of the r

Very very Harsh Geko. I see a man, in an unenviable position, doing his utmost to balance the impossible tasks of trying to control the spread of a new novel virus - for which there is no treatme

By the book...

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https://jennermuseum.com
 

They need your help, perhaps a trip to Berkeley Castle at the same time, highly recommended.

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Interesting piece in The Economist, on the identification of two chunks of human DNA, inherited from Neanderthals. One of them appears to aggravate covid infections, while the other is protective. Very uneven distribution across global populations is suggested to be associated with the regional variance in covid lethality.

As the Economist is paywalled, here's a list to a summary of the original paper: https://www.mpg.de/16433266/0216-evan-neandertal-gene-variants-150495-x

And here's the Economist link for those who can access: https://www.economist.com/science-and-technology/2021/02/24/dna-from-neanderthals-affects-vulnerability-to-covid-19?utm_campaign=editorial-social&utm_medium=social-organic&utm_source=facebook&fbclid=IwAR3UHj3HCF1kyPIWyM4lS50QYsHbb1PNMqgQh9odQgU-p2fKZGQ4vOVTFUg

Another fascinating piece of the jigsaw.

Nigel

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Nigel,  I can only read the first two paras of the Economist article, but it refers, without references, to two papers.   Would you please copy the links to those  - I'd love to read them.   If no links, are the authors or any other clues given?

Ah!  Is this one?  https://www.nature.com/articles/s41586-020-2818-3

Abstract

A recent genetic association study1 identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative)2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.

But I fear the Economist is bit slow off the mark!  That paper was cited in the Guardian last September!   Is there more?

The high incidence in people of South Asian ancestry may be revealing.     The dreadful toll of Covid on BAME people in comparison with Europeans has been attributed to poor housing, poverty and social conditions with many generations living together, but the number of Bame doctors and nurses has always been a counter to that argument.

John

Edited by john.r.davies
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Sorry John, yes the first paper, about the 'aggravating' haplotype, was the one by Hugo Zeberg and Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, in Nature.

The Economist then goes on to summarise the second, about the 'protective' haplotype, by the same authors in the Proceedings of the National Academy of Sciences, 2 March: https://www.pnas.org/content/118/9/e2026309118

Nigel

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It is an assumption that Bangladeshi Neanderthal gene sequences contribute to susceptibillity to  C-19. The genes are: SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1.  (  https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3673483

They have no obvious role in immunity to viruses. 

===

However the Nature paper gene OAS1 will be beneficial in slowing viral replication. OAS1 is a component of innate immune system. And - wait for it !! - is promoted by 1,25(OH)D.  

=

The  likely reason why SE Asians die in UK ( but not in Bangladesh) is low 25(OH)D. David Grimes recorded his patients' 25(OH)D in his Blackburn hospitals. Only 4 out of 1754 SE Asian pts had 25(OH)D above 100 nmol/L, most were badly deficient (<25 nmol/L).

Peter

 

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30 minutes ago, Peter Cobbold said:

It is an assumption that Bangladeshi Neanderthal gene sequences contribute to susceptibillity to  C-19. The genes are: SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1.  (  https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3673483

They have no obvious role in immunity to viruses. 

===

However the Nature paper gene OAS1 will be beneficial in slowing viral replication. OAS1 is a component of innate immune system. And - wait for it !! - is promoted by 1,25(OH)D.  

=

The  likely reason why SE Asians die in UK ( but not in Bangladesh) is low 25(OH)D. David Grimes recorded his patients' 25(OH)D in his Blackburn hospitals. Only 4 out of 1754 SE Asian pts had 25(OH)D above 100 nmol/L, most were badly deficient (<25 nmol/L).

Peter

 

b888er...... "......Nature paper....." should  read PNAS https://www.pnas.org/content/118/9/e2026309118

PNAS is highly respected despite its nickname Premature News About Science

Peter

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If Vit D plays a role in the immune system and reducing the impact of covid19 infection, what should we expect with regard to reactions to the vaccine based on vitamin D levels ?.  I have had both pfizer shots at this point and no reaction at all.

Stan

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25 minutes ago, foster461 said:

If Vit D plays a role in the immune system and reducing the impact of covid19 infection, what should we expect with regard to reactions to the vaccine based on vitamin D levels ?.  I have had both pfizer shots at this point and no reaction at all.

Stan

I like your thinking Stan, Roger and I have been wondering the same thing. We both had the Pfizer shot and I had no reaction, Roger had a bit of mild ache in the shot location.

I was watching our Govt Covid update on TV just now and they said that they don’t expect the older people to react as much as younger people because the “ oldies” have been exposed to far more in their lifetime and hence have more antibodies to fight of side effects.

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4 minutes ago, SuzanneH said:

I like your thinking Stan, Roger and I have been wondering the same thing. We both had the Pfizer shot and I had no reaction, Roger had a bit of mild ache in the shot location.

I was watching our Govt Covid update on TV just now and they said that they don’t expect the older people to react as much as younger people because the “ oldies” have been exposed to far more in their lifetime and hence have more antibodies to fight of side effects.

The story here is that younger people have a more aggressive immune system so a stronger reaction to the vaccine. People over 70 have little or no reaction. If Vit D plays such a major role in the immune system I would have expected Vit D level to also play a role.

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8 minutes ago, foster461 said:

The story here is that younger people have a more aggressive immune system so a stronger reaction to the vaccine. People over 70 have little or no reaction. If Vit D plays such a major role in the immune system I would have expected Vit D level to also play a role.

Although I'm no kind of expert, I believe vaccine reactogenicity is more complex than that. It seems that systemic side effects (eg flu-like stuff) is triggered by the migration of reactive products from the vaccination site into the circulation. The extent to which that happens varies and at least part of it is to do with physiological variations between individuals that are unconnected with the immune system.

This is a good article. https://www.nature.com/articles/s41541-019-0132-6

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58 minutes ago, foster461 said:

If Vit D plays a role in the immune system and reducing the impact of covid19 infection, what should we expect with regard to reactions to the vaccine based on vitamin D levels ?.  I have had both pfizer shots at this point and no reaction at all.

Stan

Its complicated and unresolved.

For flu vaccines D-deficinecy impairs resposne to soem strains but not others. But SARS-COV-2 is entirely new so flu vaccine responses may not bre a good basis. Last year I was on high D3 and had arm-ache fro 3days after the flu jab. And nothing afte the AZ C_19 jab.

However it is generally agreed that oldies are immunoscenescent and many do not responed to vaccines. I see that as a good reason ot take D3 to boost innate immunity that does not depepnd upon antiibodies, and is first in line to attack the virus. Most elderly are badly DD3 deficient.

Peterr

 

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Neat overview of D3 roles in diseases with an immune basis. Holick is eminent, discovered 1,25(OH)D ca 1970

https://www.mdpi.com/2072-6643/12/7/2097/htm

note physiological  criteria

Peter

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Just to lighten the mood somewhat, I received this from Dave Gibson and thought others might enjoy it:

The European Medicines Agency has reported on blood clots and Covid jabs.

Its conclusion:- The EU has all the clots and the UK has all the jabs.

Ian Cornish

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I have been invited by U.K. Biobank to take a Covid19 Antibody test. It is a shame that it wasn’t at this time last year as it may have proved that I had Covid19 back in Jan/Feb 2020 as I believe I did.

I have only had my first Covid19 Pfizer Biontech jab and had absolutely no reaction or side effects to it so the results of this Antibody test should be interesting, I suspect they are going to be negative.

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If you did have Covid before then it would be surprising  if you don't get a "robust" antibody response: https://www.medrxiv.org/content/10.1101/2021.01.29.21250653v1

But antigens are not the only fruit of a vaccination!  https://www.bbc.com/future/article/20210114-covid-19-how-effective-is-a-single-vaccine-dose

JOhn

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5 hours ago, SuzanneH said:

I have been invited by U.K. Biobank to take a Covid19 Antibody test. It is a shame that it wasn’t at this time last year as it may have proved that I had Covid19 back in Jan/Feb 2020 as I believe I did.

I have only had my first Covid19 Pfizer Biontech jab and had absolutely no reaction or side effects to it so the results of this Antibody test should be interesting, I suspect they are going to be negative.

Sue

Did you have any long lasting symptoms from catching it?

Edited by ntc
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13 minutes ago, ntc said:

Sue

Did you have any long lasting symptoms from catching it?

Neil, it has never been confirmed that I had it but I lost my appetite for about 3 months and lost a lot of weight, beside the very bad and long lasting cough and generally feeling bad and chesty.

It is hard to tell if I have any long lasting symptoms because I am awaiting a replacement hip operation and have been in extreme pain for over a year and am finding it very difficult to get about and get in and out of cars.

some days are better than others but in general they are bad.

It is coming up to one year since my stair lift was installed, the best present I ever had. :o

 

Edited by SuzanneH
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45 minutes ago, barkerwilliams said:

Thanks Alan, interesting, C-19 has certainly heightened interest in immune systems. The assays use primary human cells (from blood or biopsies, in short-term culture) which is good. However I cant find mention of the concentration of TBHQ used. It may have been,say, a thousand-fold higher than any avid consumer of processed foods could attain. To me that diminiishes the impact of the work.

Peter

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15 minutes ago, barkerwilliams said:

My analysis sent to the Campaign Group yesterday:

"" The art of doing science is to identify the exceptional and then follow that clue.

Hidden in the authors' melange is one paper that used 4000 IU pd over a year, and got a positve result:

https://bmjopen.bmj.com/content/bmjopen/2/6/e001663.full.pdf

The sigificnace of that study was then obliterated - extinguished - by their obsession with big cohorts.

Meta analyses fail to identify the "that's odd" data, the very stuff of doing science.

Another paper for the round file.""

In other words, its  cr*p.

Peter

 

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2 hours ago, Peter Cobbold said:

In other words, its  cr*p.

I don't understand why you are so disparaging about it. It's a meta analysis and seems on the face of it to be competently performed in that light. 

I've only had a quick read through but the paper's interpretation section starts by saying: "Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small." That seems an entirely reasonable conclusion from the analysis, given the way meta analyses are done. 

I realise that the report didn't then go on to speculate about "what ifs", eg what if more of the trials had involved much higher doses, or what if studies had looked at different disease phenomena, or whatever. But the scope of the analysis was just to say, what does the RCT evidence to date tell us about vitamin D supplementation and the risk of ARIs, and present the analysis.

That does then of course to allow individual researchers, as a next step, to explore the analysis, identify interesting correlations within the analysis, including those having small n, as a starting point for replication studies at larger scale and/or magnifying the interesting 'signal' variables (in this case, perhaps looking at higher dose levels). As you say, "identifying the exceptional then following that clue".

Nigel

 

Edited by Bleednipple
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