If you are a newly infected COVID-19 patient (or any RNA virus, for that matter), you are more likely to do worse if you contracted the virus from a close relative than if you picked up the infection from an unrelated person.
So what support is there for this somewhat outlandish theory?
You will have to look back a long time- around 400 years, to find a plausible explanation for this. In the 16th century, settlers from Europe increasingly explored the Old World (a term that refers to the Americas and Australia, but mainly the former). Over the next century or so, denizens of the Old World, mainly American Indians living in South and Central America, died off. Approximately 56 million people had died by 1650. The population shrunk by 90%. Even as late as the the 1960s and 70s, the population in some Amazonion basins had a death rate of around 75%.
So what killed them?
A key piece of evidence comes from the work of Garenne and Aaby in 1990, in which they found that a child contracting measles from a family member faced twice the risk of death than a child picking up the infection from an unrelated passerby. While it is tempting to simply attribute this to the dosage of the virus being higher in the instances where it was picked up from a family member, studies with an attenuated measles virus have disproven this by showing that the dosage of this virus while infecting a new subject has no bearing on its outcome.
In a fascinating paper published in Science in 1992, Francis L Black, epidemiologist at New Haven, CT, contended that the American Indians were mainly killed off by RNA viruses. These viruses have poor proofreading in their RNA polymerase, which leads to numerous mutations during new viral RNA production, as discussed previously in this forum. They start mutating even while the infection is progressing within an individual host. The host counters this by presenting the neo-antigens in the grooves of MHC Class I molecules on antigen-presenting-cells (APCs) to CD8 T-lymphocytes. Cellular immunity results, eventually clearing the virus. When the virus infects a new host, the process starts all over again.
However, the virus adapts during this process as well. Like all RNA viruses, it has clever ways of stymieing the immune system by hiding antigenic epitopes inside the cell, rather than on the surface, preventing antigen presentation by APCs or mimicking host antigens. When the virus passes from one host to another, if the hosts are related and therefore share MHC phenotypes, the virus, being pre-adapted, finds it easier to multiply, as it has already found a way of bypassing the adaptive immune system. It does not have this advantage if it attacks a person unrelated to the original host.
And here, the genetic homogeneity of those original American Indians became their downfall. Just to illustrate, There are 3 classes of Class I HLA antigens- A, B, and C. Most epidemiologic data is available on the first two. Thus, serological studies have identified 40 A & B alleles in 1342 sub-Saharan Africans, 37 in 1069 Europeans, 34 in 4061 East Asians, but only 10 among 1944 South Americans, 14 in 12,243 Polynesians, and 10 in 5499 Papua New Guineans. All A & B sequences in the New World also occur in the Old World.
The more alleles in a population, the less is the frequency of an individual allele, and the less likely it is that the virus will find it in its next host. Thus if the allele frequency is q, there is a q^2 chance of finding it in the next host. Black worked out that there was a 32% chance that a virus passing between 2 South Americans would not find a new MHC phenotype at either the A or B locus of the new host, but only a 0.5% chance when it passed between 2 Africans.
Thus, the less the polymorphism of MHC alleles in the host group, the more dangerous the virus is, as evidenced by the demise of those Old World denizens, who lived in a cloistered community with no intermarriage.
The same principles apply to this pandemic, albeit in a different context. COVID-19 has a very high infectivity rate, R being >3. If one happens to pick it up from a close relative, one will fare worse due to the shared MHC alleles, and thus viral pre-adaptation, than if the infection came from an unrelated source.
A 400 year old tragedy may thus have lessons for the current pandemic.
References
1. Black F. why Did They Die. Science 1992;258:1739-40.
2. Garenne M and Aaby P, ibid 1990;161:1088.
So what support is there for this somewhat outlandish theory?
You will have to look back a long time- around 400 years, to find a plausible explanation for this. In the 16th century, settlers from Europe increasingly explored the Old World (a term that refers to the Americas and Australia, but mainly the former). Over the next century or so, denizens of the Old World, mainly American Indians living in South and Central America, died off. Approximately 56 million people had died by 1650. The population shrunk by 90%. Even as late as the the 1960s and 70s, the population in some Amazonion basins had a death rate of around 75%.
So what killed them?
A key piece of evidence comes from the work of Garenne and Aaby in 1990, in which they found that a child contracting measles from a family member faced twice the risk of death than a child picking up the infection from an unrelated passerby. While it is tempting to simply attribute this to the dosage of the virus being higher in the instances where it was picked up from a family member, studies with an attenuated measles virus have disproven this by showing that the dosage of this virus while infecting a new subject has no bearing on its outcome.
In a fascinating paper published in Science in 1992, Francis L Black, epidemiologist at New Haven, CT, contended that the American Indians were mainly killed off by RNA viruses. These viruses have poor proofreading in their RNA polymerase, which leads to numerous mutations during new viral RNA production, as discussed previously in this forum. They start mutating even while the infection is progressing within an individual host. The host counters this by presenting the neo-antigens in the grooves of MHC Class I molecules on antigen-presenting-cells (APCs) to CD8 T-lymphocytes. Cellular immunity results, eventually clearing the virus. When the virus infects a new host, the process starts all over again.
However, the virus adapts during this process as well. Like all RNA viruses, it has clever ways of stymieing the immune system by hiding antigenic epitopes inside the cell, rather than on the surface, preventing antigen presentation by APCs or mimicking host antigens. When the virus passes from one host to another, if the hosts are related and therefore share MHC phenotypes, the virus, being pre-adapted, finds it easier to multiply, as it has already found a way of bypassing the adaptive immune system. It does not have this advantage if it attacks a person unrelated to the original host.
And here, the genetic homogeneity of those original American Indians became their downfall. Just to illustrate, There are 3 classes of Class I HLA antigens- A, B, and C. Most epidemiologic data is available on the first two. Thus, serological studies have identified 40 A & B alleles in 1342 sub-Saharan Africans, 37 in 1069 Europeans, 34 in 4061 East Asians, but only 10 among 1944 South Americans, 14 in 12,243 Polynesians, and 10 in 5499 Papua New Guineans. All A & B sequences in the New World also occur in the Old World.
The more alleles in a population, the less is the frequency of an individual allele, and the less likely it is that the virus will find it in its next host. Thus if the allele frequency is q, there is a q^2 chance of finding it in the next host. Black worked out that there was a 32% chance that a virus passing between 2 South Americans would not find a new MHC phenotype at either the A or B locus of the new host, but only a 0.5% chance when it passed between 2 Africans.
Thus, the less the polymorphism of MHC alleles in the host group, the more dangerous the virus is, as evidenced by the demise of those Old World denizens, who lived in a cloistered community with no intermarriage.
The same principles apply to this pandemic, albeit in a different context. COVID-19 has a very high infectivity rate, R being >3. If one happens to pick it up from a close relative, one will fare worse due to the shared MHC alleles, and thus viral pre-adaptation, than if the infection came from an unrelated source.
A 400 year old tragedy may thus have lessons for the current pandemic.
References
1. Black F. why Did They Die. Science 1992;258:1739-40.
2. Garenne M and Aaby P, ibid 1990;161:1088.
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