To Vaccinate or Not---The Rat Flu Odyssey Continues

[Mofro261]

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Also, maybe one of the smart people can answer me this--the mRNA vaccines cause the body to start making spike proteins. For how long after vaccination does that go on, or is it one copy of spike protein and then the mRNA is destroyed? Could spike protein alone give a positive result on an antigen test? If a vaccinated person were infected with SARS-CoV-2 and the immune response rapidly ended the infection, could non-infectious debris from the brief infection produce a positive test result, similar to the way recovering Covid 19 patients may test positive for some time after active infection has been stopped? Do we have tests that distinguish between live virus and nonviable viral remnants?

We don't have evidence that any vaccine prevents asymptomatic spread from occurring, mostly because tracking people as carriers without any symptoms has rarely ever been done.


mRNA is used to make protein for every protein in your body. No, it's not 1:1, it varies due to a couple different factors but mRNA can be used again and again as a template for protein synthesis, 10-1000X. These vaccine RNA's are somewhat stablized to prolong half life so they are likely to achieve the upper bound.


Antigen detection tests are looking for Nucleoprotein, not the Spike. This is because in each virus particle there are ~75 Spike trimers but on the order of 400-1000 NP proteins, so a lower detection limit can be achieved with NP. Currently these limits are on the order of ~50-100 virus particles/swab which is close to 2 orders of magnitude above rtPCR. But the Ag detection is still ~80% compared to rtPCR and prone to miss low levels of RNA- that some would argue are likely non-infectious anyway.


The Nature lit I was reading yesterday had somewhat disturbing sidenote reports of long term presence of Antigen in the intestinal biopsies.

https://www.nature.com/articles/s41586-021-03207-w
Evolution of antibody immunity to SARS-CoV-2

SARS-CoV-2 antigen persistence
Antibody evolution occurs by somatic mutation and selection in germinal centers wherein antigen can be retained in the form of immune
complexes on the surface of follicular dendritic cells for prolonged
periods of time. Residual protein in tissues represents another potential
source of antigen. SARS-CoV-2 replicates in ACE2-expressing cells in
the lungs, nasopharynx and small intestine22–25, and viral RNA has been
detected in stool samples even after the virus is cleared from the nasopharynx26–28. To determine whether there might be antigen persistence
in the intestine after resolution of clinical illness, we obtained biopsies
from the upper and lower gastrointestinal (GI) tract of 14 individuals,
an average of 4 months (range 2.8-5.7 months) after initial SARS-CoV-2
diagnosis (Supplementary Table 7). Immunostaining was performed to
determine whether viral protein was also detectable in upper and lower
GI tract, with de-identified biopsies from individuals pre-dating the
pandemic (n=10) serving as controls. ACE2 and SARS-CoV-2 N protein
was detected in intestinal enterocytes in 5 of 14 individuals (Fig. 5a–d,
Extended data Fig. 9a-h and 10a-b, and Supplementary Table 7) but not
in historic control samples (Extended data Fig. 9i-l). When detected,
immunostaining was sporadic, patchy, exclusive to the intestinal epithelium and not associated with inflammatory infiltrates (Extended
data Fig. 9a-h and 10a-b). Clinically approved nasopharyngeal swab
PCR assays were negative in all 14 individuals at the time of biopsy.
However, biopsy samples from 3 of the 14 participants produced PCR
amplicons that were sequence verified as SARS-CoV-2 (Methods and
Supplementary Table 7). In addition, viral RNA was detected by in situ
hybridization in biopsy samples from the two participants that were
tested (Extended data Fig. 10c-d) but not in historic control samples
(Extended data Fig. 10e).

NP is a weird protein that can phase seperate and form droplets with RNA, but these proteins really shouldn't persist months later without some continued replication.

[MontuckyFried]

I expected so, but thanks for confirming. It looks like the problem you're having is a misunderstanding of how mutation occurs. It's been known from very early on that this virus is itself mutation-resistant as Multiverse described, but of course resistance is not a guarantee.

So mutation potential is unknown. But what we do know is that mutation can happen during reproduction. So every infection produces about a trillion chances, so spreading the virus increases the chance of mutation in proportion to the increase in immunity as long as no mutation arises that overcomes existing immunity, which would be a complete restart: all prior immunity would be irrelevant and whatever progress toward herd immunity would be destroyed. So the math doesn't work: either this thing is mutating regularly, in which case spread increases mutations further and there can never be any benefit to spread. Or it's mutating slowly, in which case we may have time to eradicate it by preventing spread. Either way there is no benefit to spread and there is significant risk.



Me too. Can you live up to that goal when doing so requires learning facts that conflict with your present perspective?

I'm not afraid. There are no bad conditions, only bad gear. Even if this thing were to become 10 distinct variations with no overlap in immunity and all more contagious than measles, it would still be perfectly possible to avoid catching it through aerosols. It just requires a good mask. That's a reality that can be accepted and we can all get on with our lives.

400k dead may be less expensive than the other impacts to our society. Let's assume so. How many trillions of dollars would be the right number before you were willing to put on a good mask for a while? How much would we have to pay you personally not to collaborate with the virus?

All very fair points. Thanks for keeping it real, man.

Re: Mutation - I personally am not worried. However, if it's really so lethargic in mutating, then why are so many making such a stink about the UK variant, the South African one, etc.?

[MontuckyFried]

Now this is just silly. When the next war breaks out do you want the news to report on how many soldiers haven't been killed yet? Come on, man!

Because it could change our perspective into something more optimistic instead of the doom and gloom the news has been peddling to us for a year straight. Not to discount the deaths or anything, but if we also looked at the numbers as a whole, it might give us some freaking hope. That's all. It seems that every time we hear something positive, like the vaccine progress, CNN be like "NO! YOU ALL GONNA DIE! Now just stare at this death ticker for the next 72 hours."

We've had a solid year to make real, positive changes to our country's health (like our culture of shitty diets, lack of exercise, and bad habits), but nope! Mostly silence on that front. It's bizarre. This was our country's golden opportunity to get our overall health under control and it's been squandered. Very frustrating.

[The AD]

Re: Mutation - I personally am not worried. However, if it's really so lethargic in mutating, then why are so many making such a stink about the UK variant, the South African one, etc.?

Because Covid is the story of the century. The media is going to report on any developments. When new variants seems to be driving outbreaks that's big news.

[jono]

All very fair points. Thanks for keeping it real, man.

Re: Mutation - I personally am not worried. However, if it's really so lethargic in mutating, then why are so many making such a stink about the UK variant, the South African one, etc.?

Because, especially as close as we are to vaccinations which should significantly help move us toward eradication, the one thing that could derail all forms of immunity (including screwing up the vaccines' effectiveness) is this unknowable risk of a mutation showing up that is resistant. It's not the probability that is worrisome, it's the impact if it happens (remember, risk = probably x impact).

ETA: also because the probability of mutation is (hopefully) peaking now--because spread.

[The AD]

We've had a solid year to make real, positive changes to our country's health (like our culture of shitty diets, lack of exercise, and bad habits), but nope! Mostly silence on that front. It's bizarre. This was our country's golden opportunity to get our overall health under control and it's been squandered. Very frustrating.

How was this our golden opportunity, exactly? I'm not following your reasoning here.

[Mofro261]

The concern is that vaccines will target the site that is mutated in the South African variant.

Looked at the BioRxiv preprint that warns of this variant (here) and it appears to be at amino acid 484, located in a region called the receptor binding domain, or RBD of the spike protein. The mutation is from a glutamic acid residue mutated to lysine, though nobody knows how this affects virulence. From numerous prior studies, it's pretty well established that the RBD region is one of the most common targets of "natural" immune neutralization seen in most people who are infected with SARS CoV2, and preprint describes that the South African mutation allows for escape from neutralizing antibodies and T-cell response.

The mRNA vaccines prevalent in the US (Pfizer and Moderna) basically provide a dummy spike protein as target practice for the immune system (summarized here and also discusses the RBD), and would therefore likely elicit a similar response targeting the RBD.

So TL;DR: yes, my understanding is that the South African variant is worrisome in that it might allow for escape from the current mRNA vaccines used in the USA.

Of course, Pfizer and/or Moderna could (and probably will, if the situation gets dire enough) just rejigger the mRNA target to take the variant into account, but that would require re-immunizing everyone.

Would love to hear mofro's thoughts on the matter.

The E484K mutation is somehwat toublesome as it is in the middle of the lateral ridge of the RBM and affects several classes of neutralizing antibody. So far this means up to a 10x decrease in some individuals sera (post infection, not vax) at preventing the virus from binding it's receptor. This is a big deal if you have a borderline response, maybe not a big deal for vaccination as that will induce several orders of magnitude more immunity (upon boosting) than is typically seen with natural infection. There are also mulitple binding modes or surfaces on the S protein that still allow neutralization to occur that don't involve this central residue.

There are a couple mutations away from the primary neutralizing surface that are popping up and may be more concerning in the African strain as they appear to de-stabilize the Spike trimer in a way that allows it to get inside a cell more quickly, thereby shortening the time that neutralizing antibodies have to bind and prevent this event from occurring. This may also be a driver of increased transmission.

From a protection perspective, neutralizing antibody continues to be the best correlate as preventing the virus from getting in a cell has a more profound effect than killing off an already infected cell. Based on the study of some other Coronaviruses, it is thought that it takes less than 10 minutes for the virus to get inside a cell expressing Ace2 and the proper proteases, and up to 1,000 additional virions can bud from that infected cell within 10 hours. The Spike protein is loaded with both B and T cell epitopes - 1273 amino acids is a large protein so even in the absence of a strong neutralizing antibody response there should still be a decent T cell response given the epitopes for each are vastly different most of the time.

Coronaviruses do not mutate at warp speed. The SARS family of coronavirus has a reduced mutation rate because of its molecular proofreading system. Coronaviruses are somewhere around 3-5 times slower to evolve than the flu.

Scientists think the mutations currently under discussion evolved in an immunocompromised patient who remained infected for more than 100 days as well as in people who underwent convalescent plasma therapy. Those circumstances accelerated the process resulting in rapid evolution.

Even if the UK, Brazil, South African variants are not a problem for the current vaccines, the virus will continue to evolve under selection pressure as more and more people acquire immunity either through vaccines or naturally.

The evolutionary process is just one of the reasons why naturally acquired herd immunity was never going to work. Herd immunity has never been achieved through naturally acquired infections. It is only possible through mass immunization.

Yes, to all of this.

[XXX-er]

Because it could change our perspective into something more optimistic instead of the doom and gloom the news has been

We've had a solid year to make real, positive changes to our country's health (like our culture of shitty diets, lack of exercise, and bad habits), but nope! Mostly silence on that front. It's bizarre. This was our country's golden opportunity to get our overall health under control and it's been squandered. Very frustrating.

Doom and gloom because thats what it is, hard to put the positive spin on 400,000 dead other than telling people it will dissappear when the weather gets warm

And better diet and exercise would have done fuck all for Covid in America in only 1 year while a unifyed plan, getting people to mask & distance would have saved some of those dead

[Dantheman]

How was this our golden opportunity, exactly? I'm not following your reasoning here.

There's a popular notion that, despite previously failing spectacularly, a big PR push aimed at getting people to live healthier lives would be successful now because people are afraid of COVID. I'm skeptical.

[The AD]

There's a popular notion that, despite previously failing spectacularly, a big PR push aimed at getting people to live healthier lives would be successful now because people are afraid of COVID. I'm skeptical.

I'm beyond skeptical. I think there could have been a much bigger push to get people exercising at home, though. That was an opportunity lost.

[Mofro261]

I'm beyond skeptical. I think there could have been a much bigger push to get people exercising at home, though. That was an opportunity lost.

Be Best!

[XXX-er]

You are going to get 10's of millions of people who didn't believe in covid in the 1st place TO make positive lifestyle changes for Covid ?

[Dantheman]

You are going to get 10's of millions of people who didn't believe in covid in the 1st place TO make positive lifestyle changes for Covid ?

Bingo. Christ, look at how hard it's been to get people just to wear masks in public places. Those same people are suddenly going to start exercising and eating vegetables at the behest of the government for the public good? This Nanny State tyranny will not stand!

[DJSapp]

I'm beyond skeptical. I think there could have been a much bigger push to get people exercising at home, though. That was an opportunity lost.

I'm in camp skeptical. Exercise when I could sit on the couch, not get dressed, and eat my Costco size bag of potato chips while binging Netflix?

[skaredshtles]

<snip> Not to discount the deaths or anything, but if we also looked at the numbers as a whole, it might give us some freaking hope.

And yet... your statement does EXACTLY that.

[skaredshtles]

You are going to get 10's of millions of people who didn't believe in covid in the 1st place TO make positive lifestyle changes for Covid ?

Not to mention - *who* would have been responsible for putting this message out? A federal infrastructure run by Cheetolini?

It's fucking DELUSIONAL thinking.

[Danno]

hey greg, I have 8 bars of soap in a pillow case. Wanna come over for a sleep over ?
bruises heal, maybe not the emotional kind. WE shall SEE

I know you two have a sexual tension thing going on, but a) lay off the threats of violence, and b) using someone's real name in this fashion isn't exactly doxxing, but isn't appropriate either. You know his real name, good for you, but using it along with threats of violence makes clear that you're trying to make the threat more real. Knock it off.

[MontuckyFried]

Exercise when I could sit on the couch, not get dressed, and eat my Costco size bag of potato chips while binging Netflix?

And thus the reason for America getting hit particularly hard. We are the world's sickest, fattest, most Rx pill-popping country. Seems relatively few want to actually talk about that though. What did we do over the last year, though? We doubled down on those stereotypes. We shut down the gyms. We told people to stay home. We reinforced our habits of binging TV even further, buying everything on Amazon so we don't have to peel our lazy asses off the couch, so on and so forth.

Saw a morbidly obese lady in her little scooter at the grocery store in the ice cream aisle totally stocking up. Cart was packed with junk food and all manner of frozen treats. But hey! At least she was wearing a mask, so all good, right? Sadly, we haven't been successful in getting the message out there that if you REALLY want to improve your odds of surviving this thing, then get your health under control. We're focusing SO hard on masks/social distancing/vaccines that we're utterly missing the forest of nutrition/exercise/wellness through the COVID trees.

I know this is a generally fit crowd here so am preaching to the choir on this one. It's just been increasingly frustrating to see our society completely missing a great opportunity for positive transformation on this one. I too share your skepticism, but I wish we at least TRIED.

Many here look at how well Japan and others are doing in regard to COVID and say it's contact tracing, masking, etc., but seem to mention NOTHING about how they're not a country of lard asses and they eat really goddamn well. I've spent so much time over there (and around the world), I ended up picking up many good habits along the way. Our country could learn a thing or two from other countries about nutrition before placing so much blame simply on poor mask usage as many tend to do around here.

[concretejungle]

Choosing to live in Texas and then bitching about how many fat people there are is amazeballs.


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[bennymac]

And thus the reason for America getting hit particularly hard. We are the world's sickest, fattest, most Rx pill-popping country. Seems relatively few want to actually talk about that though. What did we do over the last year, though? We doubled down on those stereotypes. We shut down the gyms. We told people to stay home. We reinforced our habits of binging TV even further, buying everything on Amazon so we don't have to peel our lazy asses off the couch, so on and so forth.

Saw a morbidly obese lady in her little scooter at the grocery store in the ice cream aisle totally stocking up. Cart was packed with junk food and all manner of frozen treats. But hey! At least she was wearing a mask, so all good, right? Sadly, we haven't been successful in getting the message out there that if you REALLY want to improve your odds of surviving this thing, then get your health under control. We're focusing SO hard on masks/social distancing/vaccines that we're utterly missing the forest of nutrition/exercise/wellness through the COVID trees.

I know this is a generally fit crowd here so am preaching to the choir on this one. It's just been increasingly frustrating to see our society completely missing a great opportunity for positive transformation on this one. I too share your skepticism, but I wish we at least TRIED.

Many here look at how well Japan and others are doing in regard to COVID and say it's contact tracing, masking, etc., but seem to mention NOTHING about how they're not a country of lard asses and they eat really goddamn well. I've spent so much time over there (and around the world), I ended up picking up many good habits along the way. Our country could learn a thing or two from other countries about nutrition before placing so much blame simply on poor mask usage as many tend to do around here.

Getting people to exercise and lose weight and eat better is a great idea.

Telling them to fill up the local gym doing workouts during a pandemic is a stupid fucking idea.

The world is a complicated place. If a person can’t figure out how to exercise and lose weight and be healthier while also maintaining physical distance from others and avoiding crowded indoor public spaces they are a moron.

[seano732]

Choosing to live in Texas and then bitching about how many fat people there are is amazeballs.


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BWAHAHA.....

[The AD]

Many here look at how well Japan and others are doing in regard to COVID and say it's contact tracing, masking, etc., but seem to mention NOTHING about how they're not a country of lard asses and they eat really goddamn well. I've spent so much time over there (and around the world), I ended up picking up many good habits along the way. Our country could learn a thing or two from other countries about nutrition before placing so much blame simply on poor mask usage as many tend to do around here.

Yes, but is there any evidence at all that suggests healthy, fit people are less likely to get the virus? I agree those attributes make you less likely to be severely affected, and certainly less likely to die, but a lot of those countries also have a lot fewer cases overall.

[abraham]

I'm beyond skeptical. I think there could have been a much bigger push to get people exercising at home, though. That was an opportunity lost.

Don't you dare trample my freedoms. Don't live in fear of the family sized bucket of kfc. How dare you tax my big gulp to encourage a change in my consumption habits.
Not to discount all the people who die from obesity and diet related diseases, but double bacon cheeseburgers are damn tasty and it's my right to eat them whenever I want.

[thedude2340]

And thus the reason for America getting hit particularly hard. We are the world's sickest, fattest, most Rx pill-popping country. Seems relatively few want to actually talk about that though. What did we do over the last year, though? We doubled down on those stereotypes. We shut down the gyms. We told people to stay home. We reinforced our habits of binging TV even further, buying everything on Amazon so we don't have to peel our lazy asses off the couch, so on and so forth.

Saw a morbidly obese lady in her little scooter at the grocery store in the ice cream aisle totally stocking up. Cart was packed with junk food and all manner of frozen treats. But hey! At least she was wearing a mask, so all good, right? Sadly, we haven't been successful in getting the message out there that if you REALLY want to improve your odds of surviving this thing, then get your health under control. We're focusing SO hard on masks/social distancing/vaccines that we're utterly missing the forest of nutrition/exercise/wellness through the COVID trees.

I know this is a generally fit crowd here so am preaching to the choir on this one. It's just been increasingly frustrating to see our society completely missing a great opportunity for positive transformation on this one. I too share your skepticism, but I wish we at least TRIED.

Many here look at how well Japan and others are doing in regard to COVID and say it's contact tracing, masking, etc., but seem to mention NOTHING about how they're not a country of lard asses and they eat really goddamn well. I've spent so much time over there (and around the world), I ended up picking up many good habits along the way. Our country could learn a thing or two from other countries about nutrition before placing so much blame simply on poor mask usage as many tend to do around here.

Post your BMI

[XXX-er]

And thus the reason for America getting hit particularly hard. We are the world's sickest, fattest, most Rx pill-popping country. Seems relatively few want to actually talk about that though. What did we do over the last year, though? We doubled down on those stereotypes. We shut down the gyms. We told people to stay home. We reinforced our habits of binging TV even further, buying everything on Amazon so we don't have to peel our lazy asses off the couch, so on and so forth.

Saw a morbidly obese lady in her little scooter at the grocery store in the ice cream aisle totally stocking up. Cart was packed with junk food and all manner of frozen treats. But hey! At least she was wearing a mask, so all good, right? Sadly, we haven't been successful in getting the message out there that if you REALLY want to improve your odds of surviving this thing, then get your health under control. We're focusing SO hard on masks/social distancing/vaccines that we're utterly missing the forest of nutrition/exercise/wellness through the COVID trees.,

I know this is a generally fit crowd here so am preaching to the choir on this one. It's just been increasingly frustrating to see our society completely missing a great opportunity for positive transformation on this one. I too share your skepticism, but I wish we at least TRIED.

Many here look at how well Japan and others are doing in regard to COVID and say it's contact tracing, masking, etc., but seem to mention NOTHING about how they're not a country of lard asses and they eat really goddamn well. I've spent so much time over there (and around the world), I ended up picking up many good habits along the way. Our country could learn a thing or two from other countries about nutrition before placing so much blame simply on poor mask usage as many tend to do around here.

I think you are completely wrong,

usa missed the boat on COVID cuz they listned to trump and they are at 1245 deaths per million

sweden a nation of fit people also missed the boat on Covid are at 1065 deaths per million cuz they didnt practise the disease protocols

Canada which is less obese but not that different from USA did a half ass stab at protocols is at 486 deaths per million

I got acid dropping blue haired young friends who arent gona vax just slid thru depending on ecnichea and crystals, the god heads all want to meet/ not wear mask cuz god will save them

dog forbid we listen to what an epidemiologist tells us to do