I recently came across this presentation by Matt Parker from the Sheffield Biomedical Research Centre in the UK titled "Altered Subgenomic RNA Abundance in SARS-CoV-2 B.1.1.7 Infections"
The N (nucleocapsid) protein sequence contains another atg start codon very soon after the one for N which codes a functional frame shift protein called "9b."
9b is believed to be an innate immune suppressor. Since it's so close to the leader sequence for N 9b is expected to get made into subgenomic RNA molecules with "express me" tags on the front as well (a molecule consisting of leader sequence + TRS + atg___... for 9b), and also ribosomes that get sgN molecules might just slip and start on the atg for 9b instead of N, producing the former. Alpha appears to increase expression of it, possibly by promoting overall sgN and the rate of ribosomes slipping on sgN's to print out a 9b.
Maybe "more immune-suppressing 9b" increases pathogenicity in real life infections or maybe not. There's other immune suppressing proteins in Orf1ab which appear earlier and could have a much more important role in real life.
But at the same time, the 5' region of the N protein, where any mutations affect the regulation and expression of N (as for the 5' regions of all subgenomic RNAs including for all the structural proteins), has been a hotspot for mutation in the VOCs, basically getting as much action as the area around the Furin Cleavage Site. Whereas for Spike and the other sgRNAs the 5' regions have been extremely conserved across all VOCs. So that definitely suggests some kind of selection pressure on the gene expression machinery for N and 9b.
Wow, it's that long: "Once you are positive, there is no point testing again with N gene based qPCR for 90 days later or your positivity will simply be assumed to be a result of the residual sgRNA you have floating around from the prior infection".
This is darkly funny: "Other studies have shown the average age of death “from COVID” to be the same as the average age of death (80)."
Well isn't this special: "Studies have found over 94% of C19 deaths have 2-3 other comorbidities".
So people complaining that they were still testing Positive after weeks: "Even if you are 100% accurate with nailing SARs-CoV-2, until you start differentiating the infective virus from the corpses, you have enough false positives to create a casedemic. If you are infectious for 9 days and can be PCR positive for 90 days, 90% of the 100% accurate tests will still be quarantining people with C19 in the rear view mirror."
Mission accomplished: "What happens when you quarantine 9 immune people for every infectious person qPCR picks up? You guarantee herd immunity is never reached!"
Ollie says: "You can have him when I'm done with him".
That’s a bit of a funny paradox-invocation at the end. Throwing the immune at the infected cannot advance reaching of “herd immunity,” since the same does not directly reduce how many susceptibles are thrown at the infected. Immune people can be quarantined, beamed to Mars, etc., it doesn’t matter unless it causes them to displace or fail to displace a susceptible somehow.
Right, but they are equally a dead end if they don’t exist, or are quarantining. I mean you can suppose some scenarios with truly randomized batch exposures like a sick cashier who will see 100 people today, 20 vs 30 of whom are susceptible, but really the cashier just sees 110 people when you throw the quarantined immune back in. Or you could imagine sick cashiers being called in to cover quarantined immune cashiers; but they’re also being sent home because the quarantined immune customers. Canada, the currently most immune naive to everything country in the world, didn’t maintain below-20 N seropositivity into January 2022 because lockdowns increase herd immunity thresholds https://www.medrxiv.org/content/10.1101/2022.10.28.22281660v1
There is no “the concept” in herd immunity. It is an imprecise term with changing definitions through time and all I have done is try to parse whatever yours is. There’s no further discussion possible without derailing into semantics. My point remains uncontested by your “the math says” counter.
Right. But, again, there was a mis-parse of your use of "herd immunity" on my part. I assumed you were trying to make a point about when waves reverse in practice, in which case my counter is valid. If you are just referring to "the math formula called herd immunity" then my counter demonstrates why it doesn't have anything to do with when waves actually reverse.
The math formula called herd immunity is not a product of modern human knowledge about virus structure or immune function. It simply mathematizes assumptions about transmission and immunity that were already available from observation centuries before germ theory. As such, if it were valid, it would have been proposed by the Greeks. It isn't valid. It was invented by Sencer from the CDC in 1967 to pitch the Measles Eradication Campaign and was litigated to be false by Fox, et al. in 1971 https://academic.oup.com/aje/article-abstract/94/3/179/192686
Coincidentally N3 primer on the CDC test back in January 2020 was binding to human DNA.
Thanks for posting this Kevin.
I recently came across this presentation by Matt Parker from the Sheffield Biomedical Research Centre in the UK titled "Altered Subgenomic RNA Abundance in SARS-CoV-2 B.1.1.7 Infections"
https://www.youtube.com/watch?v=aK8zp57FIK0
I found it pretty interesting but would welcome your thoughts if you have time.
Best wishes
Lee
That was followed up in https://www.nature.com/articles/s41586-021-04352-y
The N (nucleocapsid) protein sequence contains another atg start codon very soon after the one for N which codes a functional frame shift protein called "9b."
9b is believed to be an innate immune suppressor. Since it's so close to the leader sequence for N 9b is expected to get made into subgenomic RNA molecules with "express me" tags on the front as well (a molecule consisting of leader sequence + TRS + atg___... for 9b), and also ribosomes that get sgN molecules might just slip and start on the atg for 9b instead of N, producing the former. Alpha appears to increase expression of it, possibly by promoting overall sgN and the rate of ribosomes slipping on sgN's to print out a 9b.
Maybe "more immune-suppressing 9b" increases pathogenicity in real life infections or maybe not. There's other immune suppressing proteins in Orf1ab which appear earlier and could have a much more important role in real life.
But at the same time, the 5' region of the N protein, where any mutations affect the regulation and expression of N (as for the 5' regions of all subgenomic RNAs including for all the structural proteins), has been a hotspot for mutation in the VOCs, basically getting as much action as the area around the Furin Cleavage Site. Whereas for Spike and the other sgRNAs the 5' regions have been extremely conserved across all VOCs. So that definitely suggests some kind of selection pressure on the gene expression machinery for N and 9b.
Wow, it's that long: "Once you are positive, there is no point testing again with N gene based qPCR for 90 days later or your positivity will simply be assumed to be a result of the residual sgRNA you have floating around from the prior infection".
This is darkly funny: "Other studies have shown the average age of death “from COVID” to be the same as the average age of death (80)."
Well isn't this special: "Studies have found over 94% of C19 deaths have 2-3 other comorbidities".
So people complaining that they were still testing Positive after weeks: "Even if you are 100% accurate with nailing SARs-CoV-2, until you start differentiating the infective virus from the corpses, you have enough false positives to create a casedemic. If you are infectious for 9 days and can be PCR positive for 90 days, 90% of the 100% accurate tests will still be quarantining people with C19 in the rear view mirror."
Mission accomplished: "What happens when you quarantine 9 immune people for every infectious person qPCR picks up? You guarantee herd immunity is never reached!"
Ollie says: "You can have him when I'm done with him".
That’s a bit of a funny paradox-invocation at the end. Throwing the immune at the infected cannot advance reaching of “herd immunity,” since the same does not directly reduce how many susceptibles are thrown at the infected. Immune people can be quarantined, beamed to Mars, etc., it doesn’t matter unless it causes them to displace or fail to displace a susceptible somehow.
That is not true.
Each immune person in the herd is a dead end. The more that exist in the crowd, the more dead ends buffer the immuno naive.
Right, but they are equally a dead end if they don’t exist, or are quarantining. I mean you can suppose some scenarios with truly randomized batch exposures like a sick cashier who will see 100 people today, 20 vs 30 of whom are susceptible, but really the cashier just sees 110 people when you throw the quarantined immune back in. Or you could imagine sick cashiers being called in to cover quarantined immune cashiers; but they’re also being sent home because the quarantined immune customers. Canada, the currently most immune naive to everything country in the world, didn’t maintain below-20 N seropositivity into January 2022 because lockdowns increase herd immunity thresholds https://www.medrxiv.org/content/10.1101/2022.10.28.22281660v1
No. You are misunderstanding the entire premise of herd immunity.
If a virus has an R0 of 3 and 2/3 of the people you interact with are immune, it goes no where.
If you deplete the people you interact with of immune people, you increase the likelihood of transmission to a naive person.
The immune contribute to the HIT and if you pull them from the population your HIT goes up.
There is no “the concept” in herd immunity. It is an imprecise term with changing definitions through time and all I have done is try to parse whatever yours is. There’s no further discussion possible without derailing into semantics. My point remains uncontested by your “the math says” counter.
In this case, people with natural immunity, you would call immune or fully vaccinated.
If they are removed from the population they cannot contribute to HIT.
https://www.nature.com/articles/s41598-021-00083-2
Right. But, again, there was a mis-parse of your use of "herd immunity" on my part. I assumed you were trying to make a point about when waves reverse in practice, in which case my counter is valid. If you are just referring to "the math formula called herd immunity" then my counter demonstrates why it doesn't have anything to do with when waves actually reverse.
The math formula called herd immunity is not a product of modern human knowledge about virus structure or immune function. It simply mathematizes assumptions about transmission and immunity that were already available from observation centuries before germ theory. As such, if it were valid, it would have been proposed by the Greeks. It isn't valid. It was invented by Sencer from the CDC in 1967 to pitch the Measles Eradication Campaign and was litigated to be false by Fox, et al. in 1971 https://academic.oup.com/aje/article-abstract/94/3/179/192686