Note that this paper is just a mathematical model, without any actual data, so our default stance should be skepticism. The mechanism seems unlikely, but not impossible. Respiratory droplets apparently do contain whole cells (source), so a way this could happen would be if transmission involves not just virus particles in droplets, but infected whole host cells; in that case, the surface markers of those cells could make a big difference to the initial immune response.
No, I am talking about actual ABO antigen on actual virus particles, and specifically probably on actual spike protein.
The ABO antigen is not a protein, unlike the Rh antigen (the positive/negative factor—which is not empirically relevant for disease risk unlike ABO). It is a motif of a few sugars hooked together (three particular sugars in a chain for O, and two different branched 4-sugar motifs for A and B) that is used as a component of polysaccharide chains used to decorate proteins via glycosylation. It winds up attached to loads and loads of membrane proteins made by cells. In a nonsecretor it winds up on surface proteins of blood cells and endothelial cells only, in the other 80% of the population it winds up on surface proteins on all cells.
The spike protein is COVERED with glycosylation sites. They are places on the protein that polysaccharide chains defined by the particular enzyme milieu of the cell get added. Like many glycosylated proteins they’re rather variable molecule to molecule and not precisely genetically predetermined by the protein sequence, though the protein certainly biases particular types of chains to wind up on particular pieces. In the case of the spike protein, these chains actually significantly help make sure that there’s very few places on the protein that an antibody can bind without needing to bind to the sugars, since the sugars are the same sugars that you decorate your own cells with and you thus cannot generate an immune reaction against.
If you look at the references of the paper above, you will see it has been experimentally determined for SARS, measles, and HIV that the ABO antigen winds up decorating the spike/fusion protein and that anti-A antibodies can neutralize particles created in tissue culture that expresses the A antigen. It doesn’t neutralize nearly as vigorously as antibodies raised against the protein proper, but a whole lot of the particles get neutralized in in vitro experiments. Presumably they bind to sugar chains near the receptor binding site and just physically block it from being able to touch its receptor.
So, virions made in your own body are effectively cloaked by glycosylation. But if an incoming inoculum includes a bit of glycosylation that you have antibodies against—an incompatible ABO blood type—antibodies might be able to bind to and neutralize a reasonable fraction of incoming viral particles before they are able to infect you and make virions that have your own ABO sugars.
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I am quite aware that this is only modeling. The feature is that the risk factors of different blood types line up with what you would expect if there was this blood type incompatibility of spread in which getting the virus from someone with an incompatible blood type was only 40% as likely as from someone with a compatible blood type, and that this could explain a component of the extreme dispersion seen in which some people barely spread the disease and some spread it quite freely. Definitely requires in vitro and careful contact tracing work to follow up on and see if the blood type associations are somehow a fluke with a different mechanism.
Note that this paper is just a mathematical model, without any actual data, so our default stance should be skepticism. The mechanism seems unlikely, but not impossible. Respiratory droplets apparently do contain whole cells (source), so a way this could happen would be if transmission involves not just virus particles in droplets, but infected whole host cells; in that case, the surface markers of those cells could make a big difference to the initial immune response.
No, I am talking about actual ABO antigen on actual virus particles, and specifically probably on actual spike protein.
The ABO antigen is not a protein, unlike the Rh antigen (the positive/negative factor—which is not empirically relevant for disease risk unlike ABO). It is a motif of a few sugars hooked together (three particular sugars in a chain for O, and two different branched 4-sugar motifs for A and B) that is used as a component of polysaccharide chains used to decorate proteins via glycosylation. It winds up attached to loads and loads of membrane proteins made by cells. In a nonsecretor it winds up on surface proteins of blood cells and endothelial cells only, in the other 80% of the population it winds up on surface proteins on all cells.
The spike protein is COVERED with glycosylation sites. They are places on the protein that polysaccharide chains defined by the particular enzyme milieu of the cell get added. Like many glycosylated proteins they’re rather variable molecule to molecule and not precisely genetically predetermined by the protein sequence, though the protein certainly biases particular types of chains to wind up on particular pieces. In the case of the spike protein, these chains actually significantly help make sure that there’s very few places on the protein that an antibody can bind without needing to bind to the sugars, since the sugars are the same sugars that you decorate your own cells with and you thus cannot generate an immune reaction against.
If you look at the references of the paper above, you will see it has been experimentally determined for SARS, measles, and HIV that the ABO antigen winds up decorating the spike/fusion protein and that anti-A antibodies can neutralize particles created in tissue culture that expresses the A antigen. It doesn’t neutralize nearly as vigorously as antibodies raised against the protein proper, but a whole lot of the particles get neutralized in in vitro experiments. Presumably they bind to sugar chains near the receptor binding site and just physically block it from being able to touch its receptor.
So, virions made in your own body are effectively cloaked by glycosylation. But if an incoming inoculum includes a bit of glycosylation that you have antibodies against—an incompatible ABO blood type—antibodies might be able to bind to and neutralize a reasonable fraction of incoming viral particles before they are able to infect you and make virions that have your own ABO sugars.
---
I am quite aware that this is only modeling. The feature is that the risk factors of different blood types line up with what you would expect if there was this blood type incompatibility of spread in which getting the virus from someone with an incompatible blood type was only 40% as likely as from someone with a compatible blood type, and that this could explain a component of the extreme dispersion seen in which some people barely spread the disease and some spread it quite freely. Definitely requires in vitro and careful contact tracing work to follow up on and see if the blood type associations are somehow a fluke with a different mechanism.