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I've hunted around some since my earlier post, it's apparently still at least partly speculation (and possibly wrong) but what the strain seems to have evolved is resistance to antibodies, not the vaccine per se. With so much of the virus around it has billions of opportunities to mutate so I guess it's not that surprising that it would do so. We need to squash this shit in a hurry to stop (or at least slow down) that evolutionary process.
https://www.infectioncontroltoday.co...cine-resistant
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.
I think this virus is going to keep the virology eggheads busy for many years.
There is also a different mutation , first identified in Denmark and present in California since May, that is being identified in LA area outbreaks. I think that's different from the South African variant, judging by the articles.Quote:
Originally Posted by ötzi
I would think that if necessary to keep up with mutations the new vaccines would undergo maybe a brief Phase 1 trial to make sure they're not lethal and then be released. What testing is done on each year's new flu vaccine.
One problem with vaccine resistant strains is the potential that people would need more than one vaccine if more than one variant is widely prevalent. Which means you have to make twice as much vaccine, or more.
Compounding problem though is the possibility of antibody dependent enhancement (ADE), which could potentially increase the ability of a virus to enter cells and cause a worsening of disease. Dengue virus is an example. This would not be picked up in a standard Phase I trial.Quote:
Originally Posted by old goat
Again, mofro knows the details on this.
Any of you ever play plague? More and more I feel like we are in the game. Pro tip, the key to killing all the humans in Plague is to make the disease as benign as possible in the beginning, get it to infect most of the world then mutate it to make it super deadly and vaccine resistant.
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Well doy. It's a type of coronavirus, as is the common cold. It was bound to mutate at warp speed. It's precisely why we can't get too cocky about a vaccine, although I'm sure due to the mRNA nature it'll be more beneficial than not. However, it's ALSO why the entire world has just gotta suck it up at some point and get on about our business. As this thing continues to mutate, the vaccine makers will be playing whack-a-mole like they do with the flu shot, until it splits into so many strains like the cold that it's pretty much impossible to deal with all but the most common variants.Quote:
Originally Posted by ötzi
I stopped playing it. It felt like it was a crowd sourced bio-weapons research front. Seriously.Quote:
Originally Posted by neufox47
Happy you snagged it but aren’t you like 20 years old or something?Quote:
Originally Posted by stealurface831
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Interesting prediction. Is it still your position that the goal is to get everyone infected at some acceptable pace? Curious to know which position is the cause and which is the effect for you.Quote:
Originally Posted by MontuckyFried
I think I recall from another post he works as an EMT or something like that so first responder. I’m working on obesity and smoking so I can qualify. Unfortunately most of the population of my state beat me to it by decades.Quote:
Originally Posted by Art Shirk
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. Truth is, I believe the vast majority of the world's population has already had at least SOME level of exposure to COVID-19 particles of varying degrees by this point. Obviously some more than others. Healthcare workers for example have had severe exposure and it's been brutal for that segment of the population, along with the elderly in assisted living, or multi-generational living in close quarters. The rest of us, the effects haven't been nearly as dramatic*. (...*for the most part)Quote:
Originally Posted by jono
It's been over a year since this thing kicked off. Whatever happened to "2 weeks to slow the spread"? That I understood and was totally on board. We all were. A year later and an ever-mutating coronavirus (as is their nature), yeah. I think it's nigh time we accept reality and get on with our lives. Not saying we don't exercise caution or anything. Go ahead and get yourselves vaccinated. I just refuse to live in a state of constant fear every time the talking heads at CNN try and panic us with the headline of a newly discovered COVID strain. Those guys are STILL doing the permanent on-screen death ticker. What about a life ticker? Showing us survival stats! That could give people some more hope. But nope.
I guess I've just seen the panic here too much over the course of the main COVID thread. "New mutation discovered!" "NO!" "AAAHH!!!" "SHIT!" I do find it ironic for a crowd who's had no problem hucking off cliffs, skiing balls to the wall, apres'ing at the Mangy Moose or Broken Spoke to sling some D with some new strange, and overall living incredibly risky mountain lifestyles (FKNA!) and then being utterly terrified over a virus that while yes, sucks, is not airborne ebola or anything. STD's never exactly scared this crowd away from anything. ;)
Your intellect is severely lacking. Wont bother explaining things to you.Quote:
Originally Posted by MontuckyFried
Its like the rest of us are dealing with 50m 5 year olds who lack comprehension and critical thinking skills but are convinced that they should have an equal say in everything.
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This is a popular right wing talking point that began back in April and it has been consistently proven wrong so far. At some point MontuckyFried might be right because of a self fulfilling prophecy.Quote:
Originally Posted by MontuckyFried
Or, since we now have vaccines the question is do we have the will to stop the pandemic from becoming endemic? The answer is probably not due to misinformation. Below are the most popular COVID misinformation talking points that thrived in Parler. These 'tags' were reposted thousands of times with virtually zero pushback or difference of opinion:
#OPENAMERICANOW !!
We have the Medicines !!
We have the logistics/hospitals !!
#KidsAreSafe
#NoVaccineForMe !!
We already are at #herdimmunity
#NoMask =Healthy
#Mask =Sick, vulnerable or terrorist.
#NoContactTracingForMe
#Science
#billgatesbioterrorist
Ask #DrJudyAMikovits and about #FauciTheFraud !
#USA USA USA!
#MAGA #MAGA2020
This is your conclusion? JHFC. :nonono2:Quote:
Originally Posted by MontuckyFried
Whatever it is you do for work... you should stick to it. Despite repeated attempts to help you out by others in these threads, the science doesn't appear to be within your grasp.Quote:
Originally Posted by 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.Quote:
Originally Posted by MontuckyFried
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?Quote:
I think it's nigh time we accept reality and get on with our lives.
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?
I'm not a scientist nor am I an epidemiologist. I have learned that when those are the topics, I should keep quiet and listen to the experts.
If 2 purported experts sharply disagree, I use critical thinking skills to evaluate what each is saying and what their possible motivations might be. That is the only place I might interject some of my own reasoning into a scientific/epidemiological debate such as this one, and even then, only in a limited fashion.
This points seems lost on some, who, despite no qualifications whatsoever, believe that they know the answers or believe that something they saw on FoxNews was the answer.
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!Quote:
Originally Posted by MontuckyFried
How about we wait and see how mass vaccination affects this thing? If that fails then it's probably time to start thinking about what the next phase is.Quote:
Originally Posted by MontuckyFried
Quote:
Originally Posted by old goat
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
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.Quote:
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).
All very fair points. Thanks for keeping it real, man.Quote:
Originally Posted by jono
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 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."Quote:
Originally Posted by 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.
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.Quote:
Originally Posted by MontuckyFried
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).Quote:
Originally Posted by MontuckyFried
ETA: also because the probability of mutation is (hopefully) peaking now--because spread.
How was this our golden opportunity, exactly? I'm not following your reasoning here.Quote:
Originally Posted by MontuckyFried
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.Quote:
Originally Posted by Tri-Ungulate
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.
Yes, to all of this.Quote:
Originally Posted by MultiVerse
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 warmQuote:
Originally Posted by MontuckyFried
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
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.Quote:
Originally Posted by The AD
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.Quote:
Originally Posted by Dantheman
Be Best!Quote:
Originally Posted by The AD
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!Quote:
Originally Posted by XXX-er
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?Quote:
Originally Posted by The AD
And yet... your statement does EXACTLY that.Quote:
Originally Posted by MontuckyFried
https://media.giphy.com/media/LyJ6KPlrFdKnK/giphy.gif
Not to mention - *who* would have been responsible for putting this message out? A federal infrastructure run by Cheetolini?Quote:
Originally Posted by XXX-er
It's fucking DELUSIONAL thinking. :D
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.Quote:
Originally Posted by willywhit
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.Quote:
Originally Posted by DJSapp
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.
Choosing to live in Texas and then bitching about how many fat people there are is amazeballs.
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Getting people to exercise and lose weight and eat better is a great idea.Quote:
Originally Posted by MontuckyFried
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.