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Natural genetic resistence to Covid-19

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  • Natural genetic resistence to Covid-19

    This has been controversial in the past on Tweb, I believe more research is revealing a history of regional and racial differences in the resistance to Covid-19.

    Source: https://www.nature.com/articles/s41586-020-2818-3




    The major genetic risk factor for severe COVID-19 is inherited from Neanderthals


    Nature volume 587, pages610–612 (2020)Cite this article

    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.
    Main


    The COVID-19 pandemic has caused considerable morbidity and mortality, and has resulted in the death of over a million people to date3. The clinical manifestations of the disease caused by the virus, SARS-CoV-2, vary widely in severity, ranging from no or mild symptoms to rapid progression to respiratory failure4. Early in the pandemic, it became clear that advanced age is a major risk factor, as well as being male and some co-morbidities5. These risk factors, however, do not fully explain why some people have no or mild symptoms whereas others have severe symptoms. Thus, genetic risk factors may have a role in disease progression. A previous study1 identified two genomic regions that are associated with severe COVID-19: one region on chromosome 3, which contains six genes, and one region on chromosome 9 that determines ABO blood groups. Recently, a dataset was released by the COVID-19 Host Genetics Initiative in which the region on chromosome 3 is the only region that is significantly associated with severe COVID-19 at the genome-wide level (Fig. 1a). The risk variant in this region confers an odds ratio for requiring hospitalization of 1.6 (95% confidence interval, 1.42–1.79) (Extended Data Fig. 1).

    © Copyright Original Source

    Glendower: I can call spirits from the vasty deep.
    Hotspur: Why, so can I, or so can any man;
    But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

    go with the flow the river knows . . .

    Frank

    I do not know, therefore everything is in pencil.

  • #2
    Source: https://www.nature.com/articles/s41590-021-01030-z



    A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

    Nature Immunology (2021)Cite this article
    This article has been updated

    Abstract


    SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.

    Main

    The COVID-19 pandemic has reminded us that infections are unique among diseases in their potential to rapidly cause massive morbidity and mortality worldwide. Throughout history, infectious diseases have imposed strong selection pressures on humans1,2,3. In particular, viral pandemics, including ones caused by coronaviruses, have occurred repeatedly over the last century, and probably throughout human history4,5,6,7. Clinical variability in response to infection, viral or otherwise, can be explained, at least in some individuals, by human genetic factors8. The introduction of SARS-CoV-2 to a naive population, on a global scale, has provided yet another demonstration of the remarkable clinical variability between individuals in the course of infection, ranging from asymptomatic infections to life-threatening disease9,10,11. Our understanding of the pathophysiology of life-threatening COVID-19 has progressed considerably since the disease was first described in December 2019 (refs. 12,13), but we still know very little about the human genetic and immunological basis of inborn resistance to SARS-CoV-2. Mean secondary attack rates for SARS-CoV-2 infections can reach up to 70% in specific households14,15, and a number of families have been reported in which all the members except one of the spouses are infected16, suggesting that some highly exposed individuals may be resistant to infection with this virus. Here, we review examples of genetically determined susceptibility to severe outcomes of two infectious diseases—tuberculosis (TB) and COVID-19—while covering in greater depth the three known cases of inborn resistance to infections. We then consider candidate genes directly relevant to resistance to SARS-CoV-2 infection. Finally, we propose a strategy for recruiting and genetically analyzing individuals who are naturally resistant to infection with the virus. Above all, we advocate for further studies to develop our understanding of the causal mechanisms of inborn resistance to SARS-CoV-2 infection and provide a framework for the use of this knowledge for therapeutic purposes.
    Inborn susceptibility to life-threatening infectious diseases


    Human evolution has been marked by microorganisms that are sufficiently pathogenic to exert selective pressure on genes crucial for host defense2. One of the deadliest scourges of human health is TB, which has caused an estimated one billion deaths in Europe over the past two millennia17. Paradoxically, less than 10% of humans infected with Mycobacterium tuberculosis develop TB. Since the turn of the twentieth century, the contribution of human genetics to TB pathogenesis has been deciphered through classic genetics and experimental studies18,19. More recently, rare inborn errors of immunity (IEIs), including autosomal recessive interleukin-12 receptor β1 (IL12RB1)20,21 and tyrosine kinase 2 (TYK2) deficiencies22, in particular, have been identified in a few people with TB. The broader relevance of this finding was shown when the analysis was expanded to more common variants, revealing that homozygosity for the TYK2(P1104A) polymorphism was associated with a high risk of developing TB17,23. p.P1104A homozygosity disrupts the capacity of TYK2 to mediate IL-23-dependent IFN-γ immunity to mycobacteria23. Its minor allele frequency is highest among Europeans17. An analysis of ancient DNA showed that the frequency of TYK2(P1104A) has strongly decreased over the last 2,000 years in Europe owing to strong negative selection, concomitant with the high TB burden in Europe24.

    © Copyright Original Source

    Glendower: I can call spirits from the vasty deep.
    Hotspur: Why, so can I, or so can any man;
    But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

    go with the flow the river knows . . .

    Frank

    I do not know, therefore everything is in pencil.

    Comment


    • #3
      Originally posted by shunyadragon View Post
      This has been controversial in the past on Tweb, I believe more research is revealing a history of regional and racial differences in the resistance to Covid-19.
      For starters, until you can define quantitatively how to measure race, it's not a scientific concept.

      Secondly, when you brought it up, you were arguing that people from East Asia were more likely to have genetic factors that provided resistance. Now you're saying you're right because they may have found one that confers susceptibility?
      "Any sufficiently advanced stupidity is indistinguishable from trolling."

      Comment


      • #4
        Originally posted by TheLurch View Post
        For starters, until you can define quantitatively how to measure race, it's not a scientific concept.

        Secondly, when you brought it up, you were arguing that people from East Asia were more likely to have genetic factors that provided resistance. Now you're saying you're right because they may have found one that confers susceptibility?
        Again and again not a coherent response. The references refers to research into the inherited genetic resistance to Covid-19

        You apparently did not understand the references and/or not willing to respond, More to follow . . .
        Last edited by shunyadragon; 01-07-2022, 08:47 PM.
        Glendower: I can call spirits from the vasty deep.
        Hotspur: Why, so can I, or so can any man;
        But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

        go with the flow the river knows . . .

        Frank

        I do not know, therefore everything is in pencil.

        Comment


        • #5
          Originally posted by shunyadragon View Post

          Again and again not a coherent response.
          You may want to re-read it.

          I'm always still in trouble again

          "You're by far the worst poster on TWeb" and "TWeb's biggest liar" --starlight (the guy who says Stalin was a right-winger)
          "Overall I would rate the withdrawal from Afghanistan as by far the best thing Biden's done" --Starlight
          "Of course, human life begins at fertilization that’s not the argument." --Tassman

          Comment


          • #6
            Originally posted by rogue06 View Post
            You may want to re-read it.
            No beed!

            Source: https://pubmed.ncbi.nlm.nih.gov/33397841/




            Med Sci Monit Basic Res
            . 2021 Jan 5;27:e929207.
            doi: 10.12659/MSMBR.929207

            A Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against COVID-19

            Konstantinos I Papadopoulos1, Warachaya Sutheesophon2, Somjate Manipalviratn3, Tar-Choon Aw4 5
            Affiliations expand

            Free PMC articleAbstract


            As of November 25, 2020, over 60 million people have been infected worldwide by COVID-19, causing almost 1.43 million deaths. Puzzling low incidence numbers and milder, non-fatal disease have been observed in Thailand and its Southeast (SE) Asian neighbors. Elusive genetic mechanisms might be operative, as a multitude of genetic factors are widely shared between the SE Asian populations, such as the more than 60 different thalassemia syndromes (principally dominated by the HbE trait). In this study, we have plotted COVID-19 infection and death rates in SE Asian (SEA) countries against heterozygote HbE and thalassemia carrier prevalence. COVID-19 infection and death incidence numbers appear inversely correlated with the prevalence of HbE and thalassemia heterozygote populations. We posit that the evolutionary protective effect of the HbE and other thalassemic variants against malaria and the dengue virus may extend its advantage to resistance to COVID-19 infection, as HbE heterozygote population prevalence appears to be positively correlated with immunity to COVID-19. Host immune system modulations induce antiviral interferon responses and alter structural protein integrity, thereby inhibiting cellular access and viral replication. These changes are possibly engendered by HbE carrier miRNAs. Proving this hypothesis is important, as it may shed light on the mechanism of viral resistance and lead to novel antiviral treatments. This development can thus guide decision-making and action to prevent COVID-19 infection.

            © Copyright Original Source



            More to follow . . .
            Last edited by shunyadragon; 01-08-2022, 10:55 PM.
            Glendower: I can call spirits from the vasty deep.
            Hotspur: Why, so can I, or so can any man;
            But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

            go with the flow the river knows . . .

            Frank

            I do not know, therefore everything is in pencil.

            Comment


            • #7
              Originally posted by TheLurch View Post
              For starters, until you can define quantitatively how to measure race, it's not a scientific concept.
              The references indeed do quantitatively demonstrate regional/racial differences of genetic differences of resistance to Covid-19. You have failed to respond to the references., nor have you done your own find the sources available concerning the research on the subject.

              Secondly, when you brought it up, you were arguing that people from East Asia were more likely to have genetic factors that provided resistance. Now you're saying you're right because they may have found one that confers susceptibility?
              The one reference concerning the susceptibility of people of European/Neanderthal susceptibility to Covid-19 is indeed a valid reference suporting the regional/racial , but not the only one you have failed to objectively respond to.

              First, references provided in this thread together in the previous thread do support that people of Southeast are indeed likely more resistant to Covid-19. Part of the foundation evidence for this is rate of infection, and fatalities is lowest in Southeast Asia.and lower in Asia in general than the rest of the world. This correlates well with the likely origin of Covid-19 and related historical viruses like the previous SARS originating from animals of Southeast Asia and South China..

              More to follow . . .
              Last edited by shunyadragon; 01-10-2022, 08:21 AM.
              Glendower: I can call spirits from the vasty deep.
              Hotspur: Why, so can I, or so can any man;
              But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

              go with the flow the river knows . . .

              Frank

              I do not know, therefore everything is in pencil.

              Comment


              • #8
                Originally posted by rogue06 View Post
                You may want to re-read it.
                Watching Shuny take on the Lurch is... um.... painful.
                The first to state his case seems right until another comes and cross-examines him.

                Comment


                • #9
                  Originally posted by Cow Poke View Post

                  Watching Shuny take on the Lurch is... um.... painful.
                  Failure to respond coherently to the numerous references is indeed painful, in particular the reference that demonstrates a generic resistance to Covid-19 in Southeast Asia, and the reference that demonstrates that descendants pf European/Neanderthals are genetically more susceptible to infection by Covid=19.

                  Can you provide any references that refute my position?

                  The silence is deafening
                  Last edited by shunyadragon; 01-10-2022, 08:45 AM.
                  Glendower: I can call spirits from the vasty deep.
                  Hotspur: Why, so can I, or so can any man;
                  But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                  go with the flow the river knows . . .

                  Frank

                  I do not know, therefore everything is in pencil.

                  Comment


                  • #10
                    Originally posted by shunyadragon View Post

                    Failure to respond coherently to the numerous references is indeed painful, in particular the reference that demonstrates a generic resistance to Covid-19 in Southeast Asia, and the reference that demonstrates that descendants pf European/Neanderthals are genetically more susceptible to infection by Covid=19.
                    Trying to define away anything you don't want to hear as "not coherent" isn't an argument. Nor is your own reading comprehension failure evidence.

                    Let's look at the abstract of the first paper you linked in this thread - specifically the last sentence of it. Now, I realize reading all the way to the last sentence of a paragraph can be hard for some people, but there's often valuable information there, so it's worth your time to struggle through. To save on the pain, I'll just quote it here:
                    "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."

                    What does that tell us? Several genomic studies have identified only a single risk factor for severe COVID. The genomic region is most commonly seen in Asian populations. In other words, it indicates that, if we only consider genetic risks, people originating from south Asia are at highest risk of severe COVID. You are using that as evidence to support your claim that risk is "lower in Asia in general than the rest of the world".

                    My silence was because your own reference refuted your argument, and even after I pointed it out, you didn't seem capable of grasping it. If there's a coherence problem here, that's it.
                    "Any sufficiently advanced stupidity is indistinguishable from trolling."

                    Comment


                    • #11
                      Originally posted by TheLurch View Post
                      Trying to define away anything you don't want to hear as "not coherent" isn't an argument. Nor is your own reading comprehension failure evidence.

                      Let's look at the abstract of the first paper you linked in this thread - specifically the last sentence of it. Now, I realize reading all the way to the last sentence of a paragraph can be hard for some people, but there's often valuable information there, so it's worth your time to struggle through. To save on the pain, I'll just quote it here:
                      "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."

                      What does that tell us? Several genomic studies have identified only a single risk factor for severe COVID. The genomic region is most commonly seen in Asian populations. In other words, it indicates that, if we only consider genetic risks, people originating from south Asia are at highest risk of severe COVID. You are using that as evidence to support your claim that risk is "lower in Asia in general than the rest of the world".

                      My silence was because your own reference refuted your argument, and even after I pointed it out, you didn't seem capable of grasping it. If there's a coherence problem here, that's it.
                      Nothing refuted and still no responseon your part that is meaningful.

                      From the reference: Elusive genetic mechanisms might be operative, as a multitude of genetic factors are widely shared between the SE Asian populations, such as the more than 60 different thalassemia syndromes (principally dominated by the HbE trait) We posit that the evolutionary protective effect of the HbE and other thalassemic variants against malaria and the dengue virus may extend its advantage to resistance to COVID-19 infection, as HbE heterozygote population prevalence appears to be pos itively correlated with immunity to COVID-19. Host immune system modulations induce antiviral interferon responses and alter structural protein integrity, thereby inhibiting cellular access and viral replication. These changes are possibly engendered by HbE carrier miRNAs. Proving this hypothesis is important, as it may shed light on the mechanism of viral resistance and lead to novel antiviral treatments. This development can thus guide decision-making and action to prevent COVID-19 infection.
                      Glendower: I can call spirits from the vasty deep.
                      Hotspur: Why, so can I, or so can any man;
                      But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                      go with the flow the river knows . . .

                      Frank

                      I do not know, therefore everything is in pencil.

                      Comment


                      • #12
                        A little note on the use of the term "race" vs. the concept of ethnic groups and regional populations. It's easy to dismiss this as "there go those liberal scientists again, avoiding a term just because it's not PC". But the term has always been poorly defined, and has been increasingly difficult to square with modern molecular evidence.

                        In Darwin's time, "race" seemed to imply something that might now be termed a subspecies - a population within a species that had some distinct identifying characteristics. The problem was that those identifying characteristics were typically based on physical appearance, and we now know that's often a poor stand in for the underlying genetics. A species that all looks identical to us can have multiple populations all with DNA differences that are larger than we typically see between clearly distinct species. And if we look at the DNA of what we thought were distinct subspecies, we can often find evidence of significant gene flow between them.

                        This gets especially problematic when it comes to humans. Humanity originated in Africa, and has had the most time to develop distinct populations there; yet historically, we've tended to lump all of them together as "Black" based on appearance. But appearance hides the genetics of Africa, which are incredibly complicated. There are some populations that have remained largely genetically isolated, and might qualify as a "race" based on seemingly forming a distinctive branch of our human family tree. But others are most certainly not. East Africans have had a lot of intermixing with Middle Eastern populations. Most of Central and Southern Africa has had its genetic completely churned up by the Bantu Expansion. And there's a tendency to lump African Americans in that, even though the population largely originated only from a few regions of West Africa, and then saw significant European DNA introduced.

                        Similarly, Native American populations are the products of two distinct migrations into North America (the Inuit arrived separately), and further back, are a mixture of East Asian populations and a now lost population with a strong similarity to Eurasian groups. The Pacific islands have at least three distinct populations present, and the degree of mixture among them varies between island groups. Etc. etc.

                        So it doesn't make any sense scientifically to lump all these different populations into large categories for any sort of scientific analysis, which is why race has mostly fallen out of favor, despite the fact that the societies science operates in continue to view it as very significant. (This has lead to some awkward conversations where young scientists are convinced that race is a real thing, but flounder when asked to define it). Instead, most studies tend to focus on much smaller populations that we know have a strong genetic similarity, and can actually define how often they may have interbred with other populations.
                        "Any sufficiently advanced stupidity is indistinguishable from trolling."

                        Comment


                        • #13
                          Originally posted by shunyadragon View Post

                          Nothing refuted and still no responseon your part that is meaningful.
                          You can repeat that all you want; it's clear that other people here have sufficient reading comprehension to understand what I'm saying. If everyone but you gets it, then it's a fair indication that the problem is yours.

                          Originally posted by shunyadragon View Post
                          From the reference: Elusive genetic mechanisms might be operative, as a multitude of genetic factors are widely shared between the SE Asian populations, such as the more than 60 different thalassemia syndromes (principally dominated by the HbE trait) We posit that the evolutionary protective effect of the HbE and other thalassemic variants against malaria and the dengue virus may extend its advantage to resistance to COVID-19 infection, as HbE heterozygote population prevalence appears to be pos itively correlated with immunity to COVID-19. Host immune system modulations induce antiviral interferon responses and alter structural protein integrity, thereby inhibiting cellular access and viral replication. These changes are possibly engendered by HbE carrier miRNAs. Proving this hypothesis is important, as it may shed light on the mechanism of viral resistance and lead to novel antiviral treatments. This development can thus guide decision-making and action to prevent COVID-19 infection.
                          Yeah, that second reference is garbage. In its entirety, it's a single correlation and boatloads of speculation built on it.

                          Is the correlation actually informative? They present no evidence that it is other than a single graph. But let's take a moment to look more carefully at that graph. It's got a good selection of Southeast Asian countries and then... random stuff. There are absolutely no African populations, even though a number of countries in that region, most notably South Africa, have excellent public health monitoring and solid COVID data. That absence is significant because it's positing that the protective effect of thalassemias could be mediated by the same properties that confer malarial resistance.

                          In sharp contrast to South Africa, it's widely recognized that India's public health services could not get reliable numbers on the pandemic, so their official counts should not be trusted. Yet that is on the graph. All of South America is represented by Brazil, where the dynamics of the pandemic were largely defined by government hostility towards public health measures, not any sort of genetic influence. There's a number of countries that did have a strong public health response - Taiwan, Hong Kong - that clearly had low numbers of COVID cases accordingly.

                          Overall, the graph that is central to the whole argument is a random mix of stuff and doesn't seem to be evidence of anything.

                          I look forward to you failing to engage with any of that information.
                          "Any sufficiently advanced stupidity is indistinguishable from trolling."

                          Comment


                          • #14
                            Originally posted by TheLurch View Post
                            You can repeat that all you want; it's clear that other people here have sufficient reading comprehension to understand what I'm saying. If everyone but you gets it, then it's a fair indication that the problem is yours.


                            Yeah, that second reference is garbage. In its entirety, it's a single correlation and boatloads of speculation built on it.

                            Is the correlation actually informative? They present no evidence that it is other than a single graph. But let's take a moment to look more carefully at that graph. It's got a good selection of Southeast Asian countries and then... random stuff. There are absolutely no African populations, even though a number of countries in that region, most notably South Africa, have excellent public health monitoring and solid COVID data. That absence is significant because it's positing that the protective effect of thalassemias could be mediated by the same properties that confer malarial resistance.

                            In sharp contrast to South Africa, it's widely recognized that India's public health services could not get reliable numbers on the pandemic, so their official counts should not be trusted. Yet that is on the graph. All of South America is represented by Brazil, where the dynamics of the pandemic were largely defined by government hostility towards public health measures, not any sort of genetic influence. There's a number of countries that did have a strong public health response - Taiwan, Hong Kong - that clearly had low numbers of COVID cases accordingly.

                            Overall, the graph that is central to the whole argument is a random mix of stuff and doesn't seem to be evidence of anything.

                            I look forward to you failing to engage with any of that information.
                            Failure to respond coherently. Race in and of itself is NOT AN ISSUE here. There have been a number of references form different sources in these two threads, and you are splitting meaningless frog hairs.
                            Glendower: I can call spirits from the vasty deep.
                            Hotspur: Why, so can I, or so can any man;
                            But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                            go with the flow the river knows . . .

                            Frank

                            I do not know, therefore everything is in pencil.

                            Comment


                            • #15
                              Originally posted by shunyadragon View Post

                              Failure to respond coherently.
                              Lurch's comments are far more coherent than yours. If you find his posts incoherent, then highlight the incoherent sections rather than dismissing the entire post. You might then get a rephrasing that you understand.

                              Jorge: Functional Complex Information is INFORMATION that is complex and functional.

                              MM: First of all, the Bible is a fixed document.
                              MM on covid-19: We're talking about an illness with a better than 99.9% rate of survival.

                              seer: I believe that so called 'compassion' [for starving Palestinian kids] maybe a cover for anti Semitism, ...

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