Can anyone with more knowledge on this topic than me (I’m no expert) assuage my fears: by giving human populations such artificial resistances (non-live vaccines) we run the risk of selecting for viruses that are even harder for even our own immune systems to detect and destroy. Current Covid strains don’t seem all that bad, basically everyone I know has been infected now. Might we run the risk of making things worse at this point?
Evolution is climbing mount improbable. And natural selection (even in the face of in this case intelligently designed selectors) funnels organisms into potential dead ends which they can’t evolve out of - they’ve gone up the ‘north face’ and in order to reach fitness in the face of their selectors, they actually need to be on a completely different mountain.
An antibody that dead ends all current evolutionary trends for an organism means that they can’t evolve out of the dead end natural selection has funnelled it down.
So no, this isn’t a ‘might make it worse’, this is a ‘end of covid’ agent.
That’s if the antigenic trigger can be made into a vaccine. More likely what the research is describing is that it is now possible to make a monoclonal antibody that can work as an infusion and is active against all known and future possible variants with the same efficacy.
> Once the virus has bound to ACE2, it must complete a final step: fusing its outer membrane with the membrane of our cells. This throws the door open to infection. Using a novel live-cell imaging platform, Alex Kreutzberger, HMS instructor in pediatrics at Boston Children’s, and Tomas Kirchhausen, professor of cell biology in the Blavatnik Institute at HMS and professor of pediatrics at Boston Children’s, showed that SP1-77 blocks this step.
> “SP1-77 binds the spike protein at a site that so far has not been mutated in any variant, and it neutralizes these variants by a novel mechanism,” noted Kirchhausen. “These properties may contribute to its broad and potent activity.”
Questions:
* If mutations at this site are possible, how would this be an evolutionary deadens in a way that the current evolutionary dynamics of the virus are not?
* Surely a lack of mutations at this site, on their face, imply only that there is no evolutionary pressure on the site and its phenotypes, and, that mutations at this site are as viable as anywhere else?
* Or, is it possible that the lack of mutations (presuming that this is very accurate) indicates an evolutionary pressure to maintain functionality that is sensitive to failure due to even minor mutations or deviations in functionality?
> If mutations at this site are possible, how would this be an evolutionary deadens in a way that the current evolutionary dynamics of the virus are not?
* Surely a lack of mutations at this site, on their face, imply only that there is no evolutionary pressure on the site and its phenotypes, and, that mutations at this site are as viable as anywhere else?
* Or, is it possible that the lack of mutations (presuming that this is very accurate) indicates an evolutionary pressure to maintain functionality that is sensitive to failure due to even minor mutations or deviations in functionality?*
the answer is that something that is so highly conserved across so many variations is mission critical. Mutations occur through replication everywhere, randomly. Highly conserved means that a change is a breaking change, severely impacting fitness, if no mutations have been observed elsewhere. Ie to extend the analogy, that point is the 'mountain' SARS-CoV-2 has decided to scale.
Thanks!
Can’t help but wonder how conserved the relevant site actually is.
I wonder because targeting such a site seems to me like the premise of this kind of research: find “mission critical” highly conserved genes and then clinically target them.
And yet, scanning the paper’s abstract and introduction (the paper is linked in the posted article) I couldn’t find any mention of any highly conserved genome site. As a layperson I may have missed it, but still, if it’s a fundamental premise, I would have expected a conspicuous statement.
Instead, the paper reads to me like one concerned with a novel method for developing new antibodies with new methods of action. Not, as the article states, mechanisms of action against “mission critical” genes.
If I’m wrong, please let me know. But at the moment, I’m suspecting a misstep on the part of the scientific journalism here.
>’SP1-77 binds the spike protein at a site that so far has not been mutated in any variant’
Is the section you are looking for that says ‘this section is highly conserved throughout all known variants’.
The novel method appears to be the the humanisation of mouse cells - ‘The researchers first inserted two human gene segments into the mice. This pushed the mice’s immune cells to quickly produce a diverse repertoire of antibodies resembling those our bodies might make.’
Since that’s all the detail they give it’s not possible for me to comment on just how unique this technique is, because humanisation of mouse white cells isn’t totally unprecedented, so maybe there’s some scientific press release licence here
I believe your quote is from the article posted here. I was talking about the paper, which I only read lightly.
Checking now the Results section of the paper, they do address how conservative the relevant genome site is, extracted below (emphases mine). TLDR: very but just short of completely conserved. Seems hopeful.
---
> Comparison of SP1-77 footprint to the mutations on the RBD of variants.
When the SP1-77 footprint was projected onto modeled RBDs from different SARS-CoV-2 variants (Fig. 5, A and B), it was evident that most mutations were located outside of the SP1-77 binding site, except for the Arg346Lys in the Mu and Omicron-BA.1.1 variants, and the Gly339Asp and Asn440Lys in all current Omicron sub-variants (50).
The modeled interfaces of SP1-77 bound to the Mu and Omicron RBDs, based on the SP1-77/G614 S complex, indicated that the conservative Arg346Lys mutation would preserve the interaction with HC CDR3 and would not have much impact on binding. Likewise, the Gly339Asp and Asn440Lys mutations were at the edge of the SP1-77 epitope with their side chains pointing away from the binding interface, explaining why Omicron variants were sensitive to SP1-77 neutralization (Fig. 5C).
While mutations near the Asn343-glycan in Omicron reconfigure the orientation such that the carbohydrate projects away from the protein surface (51), such mutations had minimal impact on binding and neutralization activity of SP1-77 (Fig. 5C).
Thus, these studies provided a structure-driven hypothesis for why SP1-77 potently and broadly neutralized all tested SARS-CoV-2 variants through Omicron BA.5.
Finally, we compared the SP1-77 footprint with the new mutations on the recently emerged BA.2.75 sub-variant. The N460K mutation in BA.2.75 was far from the SP1-77 footprint (Fig. 5, A and B); while the BA.2.75 G339H and G446S mutations were close to but did not overlap with SP1-77 footprint as described for BA.1.
These findings made us hopeful that SP1-77 also will bind and robustly neutralize BA.2.75.
If you never see bullet holes in some part of a fuselage, it likely means those planes that do have holes in those places never return home that they are vulnerable area which require more armor.
https://en.wikipedia.org/wiki/Abraham_Wald
If you don't see some part of a virus ever mutate, it marks a vulnerable location.
> * Or, is it possible that the lack of mutations (presuming that this is very accurate) indicates an evolutionary pressure to maintain functionality that is sensitive to failure due to even minor mutations or deviations in functionality?
Yes -- A lack of mutations on the site is a strong hint that it is functionally important. If virions with mutations at this site were equally fit, you'd expect more variation.
How are we sure it is a dead end and how sure are we? It sounds as if this would put extraordinary selective pressures on the virus, if we are wrong I’d fear we would just make things worse
This is basic evolutionary theory that has been subsequently played out in both the lab and in the wild. You can't prove a negative but your requirement for reassurance will only be assuaged by furthering your own understanding of evolution on a molecular level, it doesn't seem like anything I could say to you in a reply to an internet post would make the slightest bit of difference to your skepticism and you'd have to get the basic grounding in yourself. The full answer would require 3-4 years of fulltime study, the shorter answer could be arrived at by reading the blind watchmaker and climbing mount improbably, two highly accessible books on evolutionary biology
I actually asked ‘how sure are we’ - you’re right though, just saying - learn more about it - isn’t exactly helpful. If it is as ‘basic’ as you say maybe you could explain it rather than just appeal to authority.
I think OP is trying to say this is a complex field which requires a long-form medium (books, at minimum) to explain the current evolutionary theory work to a layman. But among researchers in that field this falls within the "basics", and so barring a fundamental upheaval of a lot of well-observed theories (outlined briefly in those books) we're in the clear.
I think this is fair, even if a bit frustrating that the explanation can't be broken down simpler to laymen.
I’m sorry but I can’t state this any more plainly without this turning into a lecture. It is basic evolutionary biology, in as much as gravity keeps your feet attached to the ground. It is not an appeal to authority, it is simply a statement of fact and an underlying premise of a complex field. You seem like the sort of person who likes doing your own research - I’ve given you the key to the door now you just have to walk through it
This is what I was getting at - almost nothing in my scientific field is 100% and I find that true of most things. Thus my question- how sure are we. If we are at six sigma levels great, but I find that at odds with the little I do know.
Quit being so hostile, if you are not interested in discussion I would recommend not spending time on discussion boards.
You first spoke as if it was an absolute certainty ("This is basic evolutionary theory") and now are saying, "all of the normal caveats apply" which is exactly what I was getting at in my OP thread. The "normal caveats"/edge cases are exactly what this whole discussion is about. Clearly we are speaking past one another, I apologize for my role in whatever went wrong here.
I'm sorry you're interpreting my comments as hostility, but basically you're being a the sort of commenter that it isn't really worth engaging with. You're not interested in my answers, and you've accused me of using arguments from authority. From my perspective you seem intent on finding some loophole where i'm either lying to you or i'm incorrect. In a message board format, particularly with the number of outright bad actors when it comes to anything COVID related, how is it actually in my interest to provide you with a freshman course on molecular biology?
The problem is you haven't grasped that they're actually the same answer. It can be true that a field driven by stochastic behaviour consists mostly of degrees and probabilities, and still, due to the realities of how evolution and natural selection work, mean that it is impossible for an extremely highly conserved component of spike protein to jump to a new configuration, that at the same time escapes antibody response for the conserved region and maintains any degree of fitness in the wild.
Please park your antagonism and if you are actually interested, walk through the door and explore the field yourself. It's fascinating
> mean that it is impossible for an extremely highly conserved component of spike protein to jump to a new configuration, that at the same time escapes antibody response for the conserved region and maintains any degree of fitness in the wild.
See this is exactly the sort of quantification I was asking for from the beginning (albeit still somewhat vague). Others in the thread have already answered most of my questions (read the other threads if you like) but you just kept talking past them until now. I appreciate you taking the time to respond.
> walk through the door and explore the field yourself. It's fascinating
That is precisely what I am trying to do here because I do find it fascinating as well. I have to be allowed to ask questions (even stupid ones) and I do those primarily in discussion forums like HN.
Well if it isn't then you just make other antibodies that treat the one that you can't deal with. Like it's a dead end at current time with current understanding. And as for making things worse, well it could or it could make things better by becoming lesser variant.
if all oxygen in the air was suddenly (by magic) replaced by carbon dioxide it would put extraordinary selective pressure on humans to evolve something other than oxygen-depending lungs. the most likely outcome would be that we'd all die instantly though.
I like the metaphor! I'd suggest two points, if humans evolved as fast as viruses and we couldn't replace all the oxygen on earth at once (and likely not at all in some places just as we can't get vaccine everywhere at once and not in some places at all) I would think it far more likely for human evolution to figure it out. Unlikely still, but maybe not outside the realm of possibility?
In keeping with the metaphor though and as others have pointed out in the thread - non oxygen lungs wouldn't make humans super humans, just different and if anything more likely to be weaker than their oxygen breathing counterparts as they adapt to a new environment? I think that is the running idea I'm getting at least.
> by giving human populations such artificial resistances (non-live vaccines) we run the risk of selecting for viruses that are even harder for even our own immune systems to detect and destroy
I can put your fears to bed. That shouldn't happen. How vaccines work is they teach a very specific signature to our bodies so it can be destroyed as soon as it appears. . Therefore, any selection pressure would just be to not have that signature. But, since that signature is only valuable because it is recognized, there's no great loss if it becomes meaningless. So no supervirus issues. This is different from overusing antibiotics, because the selection there is not on signatures, but instead a more general "robustness" to the poison (well, poison to the bacteria).
Some of foremost vaccine companies and medical experts in the world all but promised the COVID vaccines would give immunity to the disease and prevent it being transmitted.
So they really have far less of a grasp of vaccine effects in even that a very narrow situation than you would think. So I don't think you can just put this to bed with a few sentences starting with "it shouldn't happen"!
Are you saying that because the number of possible signatures is so vast and the vaccines so specific, even if they get slightly broader it isn’t going to make things worse because in the grand scale of things we aren’t really walling too much off?
I'm saying that at most using the vaccine will cause a virus to evolve that it evades the vaccine. It won't get any other supervirus properties, become worse, or otherwise change. The concern with using antibiotics (for instance) is that a bacteria becoming immune to one becomes more resistant to all and it's hard to generate new antibiotics. On the other hand, with the vaccine, you just might need a booster with a different signature. There's no "broadening". It's just different.
So, a vaccine's immunity might not last forever. And?
To the contrary, viruses are not intelligent, when mutations happen at random, the best way to prevent mutation is to prevent infection and length of infection.
I think what they are saging is that something that kills perfectly, every time does not generate selective pressure. The virus would have to lose the signature completely randomly.
Whereas antibiotic resistance is something that could develop because antibiotics could be under doses so individuals survived partial exposure or perhaps they worked by a mechanisms which already had some resistance in the population.
It's like, you can breed high lung capacity mammals by having them live in water but you would just kill the species if you jumped straight into holding them underwater for 20 minutes.
Something has to be survivable to genetate selective pressure.
In that case, shouldn't we never give vaccine to people with poor immunity system or with immunocompromised condition, and rather just let them be or even die? If this is true (even though difficult to actually implement in the society due to humane consideration), what happens to the vaccines of viruses like HIV? The patients already have weak immune system.
I guews if you were blindly trying to breed the most durable individual specimems. But humams have major adaptatioms aside from immunity. We have cooperation and the ability to help each other. Is it worth it to let the town butcher or carpenter keel over to secure a small increase in generarional immunity?
Native Americams had no choice but to go the route of inherited immunity when they began contracting Eurasian diseases. Was it worth living through a literal apocalypse to gain immunity?
Key flaw with this is the presumption that the required mutations are not already present in the population. Even if they are rare, it is a facile process for natural selection to make said set of mutations dominant. If a small amount of recombination (I don't know if this is occurring with COVID-19) or novel mutation is required, again, it's a fairly straight forward affair unless we're close to an eradication scenario. "Life finds a way", as they say.
I think the only reasonable response to the parent query is to address the core issue ... are there non-overlapping capabilities between "artificial" and "natural" antibodies apart from the speed and health-risk of their development/inoculation. In other words, is "artificial" immunity a better form of immunity in a way that "natural" immunity can never match? If so, seems like a pretty obvious case of "lock in".
Without being an expert, I imagine it isn't a trivial question to answer, as the evolutionary capabilities of a pathogen are a key factor, and well, we're still wrestling with predicting protein folding.
But it is always going to continue to spread won’t it? A vaccine may slow it down which is good but my fear is that long term non-live vaccines like this could just make things worse when used with such a volatile virus.
Precisely the reverse: attenuated virus (live virus) vaccines regularly allow mutation back to pathological forms. See: polio. This is because an attenuated virus is still replicating viral particles and every replication is a lottery ticket that the virus might mutate back.
mRNA vaccines, by contrast, causes no viral replication so the virus doesn't get these lottery tickets.
Of course, either type of vaccine is going to place evolutionary pressure on a disease to evolve an escape. That's just what happens.
One side note: one of the things about mRNA vaccines is that they can be very specific. Now, that may not be great for Covid where we would like to be more general. However, that may be absolutely essential against Epstein-Barr where a chunk of the virus looks like nervous system proteins. A standard vaccine is likely to prime the immune system just like the virus and cause multiple sclerosis as a side effect. An mRNA vaccine, by contrast, could target only those sections of the E-B virus that look sufficiently different from the nervous system and prime the immune system without risking friendly fire.
I obviously can't say for sure, but given the topic was the development of artificial resistance to vaccines, I would've thought the alternative they had in mind was natural resistance - i.e. getting infected naturally.
Just in my non-expert head - a live vaccine is using the virus as it already exists to confer immunity - not trying to code against a ton of hypothetical variants which could select for more radical variants
Ah, that isn't how a live vaccine works though. They get attenuated (aka damaged/killed/broken) or similar but not the same viruses (aka cowpox used to be a live vaccine for smallpox), then introduced. The body reacts to the not-really-functional virus, but it isn't the same as if it was an actual infection.
It still triggers the immune system, but mutations in any of the major receptors or the like will cause it to be less effective too.
It's wrong to say they usually don't, it's that the deadlier variants haven't lived long enough for us to remember them or have to worry about them at this moment. They still happen and can wipe out populations, and thus die out, as well. They can also reach an equilibrium where they maim many of their hosts, more than we'd like, without killing them all.
Mutations are random, nothing really is preventing a virus from replicating rapidly and killing a lot of its hosts in the short term, it's just the long-term evolutionary advantage of such traits are small, because killing hosts quickly reduces replication, potentially.
But that doesn't stop viruses and bacteria from mutating into something deadly and killing a lot, or all, of its hosts. However just that has happened throughout evolutionary history on Earth, and even in humans' history. We've seen plenty of pandemics wage war against humans and cause considerable casualties.
There's also plenty of equilibria deadly viruses can reach with their hosts, where they kill a relatively large amount of hosts, but not enough to wipe them out.
It does answer the question. Evolution is the result of mutations propagating through reproduction. The more copies of a virus replicating, the higher chances of mutation causing a more deleterious and/or virulent variant of the virus. As the number of viral copies and replications approaches zero, the chances of a worse strain of the virus spreading also approaches zero. Vaccines reduce viral load and spread, thus reducing the chances of mutation and spread of worse variants.
An example of this happening is the Spanish flu, which was a mutation of the common flu that was widespread and uncontrolled with vaccines at the time.
Drug-resistant bacteria are the result of misuse and incomplete use of antibiotics, and the environmental spread from waste of antibiotics. Also, bacteria can share genes horizontally, meaning resistance in one species can transfer to another quickly.
Antibiotic resistance in bacteria is mainly from misuse in humans and animals, and disease spread between the two, along with ineffective waste treatment and the leaching of antibiotics into the environment[1]. About 80% of antibiotics sold in the US are used in agriculture[2], where they are given to animals not to treat infections, but to prevent them and to stimulate growth. Over 60% of infectious diseases in humans are spread from animals, and 75% of new diseases in humans are spread from animals[3]. Shooting a few micrograms of vaccines into humans' arms is nowhere near the scale of antibiotic use or accumulation in the environment.
It's also possible to achieve herd immunity with vaccines, whereas antibiotics do not leave lasting immunity. To be effective, antibiotics must be taken when there's a bacterial infection, and their effectiveness diminishes as they leave the body.
Are these "worries" consistent? Where is the worry that polio vaccination might create worse strains of polio?
By cutting down the population of live covid virus particles in the wild, that is, living in human hosts, the possibility of a hard to kill variety to evolve will diminish by a very big probability.
In fact, the new more dangerous varieties are theorized to have evolved in single individuals, who lack a strong immune system, and can't kill a single virus infection for months, and then the virus accumulates changes over these months before jumping onto the general population.
> by giving human populations such artificial resistances (non-live vaccines) we run the risk of selecting for viruses that are even harder for even our own immune systems to detect and destroy
That'd be a valid question if we didn't ready have non-live vaccines with very good proven track records for polio, hepatitis, the flu, etc.
> Current Covid strains don’t seem all that bad, basically everyone I know has been infected now.
And here comes the covid denial argument. Relentlessly repeating the same loaded arguments again and again.
> Might we run the risk of making things worse at this point?
Yeah, but what about wind turbine's rare earth ? It's really polluting ! And what if climate change has more benefits than problems once we have adapted, uh ?
To be fair, you are stigmatizing someone for offering a correct observation (that the successive COVID variants have proven less debilitating and deadly) and for asking a question that must be on many people’s minds: can monoclonal antibody administration promote resistance analogous to bacterial antibiotic resistance?
Be aware that live virus vaccines are certainly not monoclonal antibody injections.
As well, rather than spending your mental energy developing excuses to dismiss, why not think on the subject at hand? You should wonder why this mouse model produces broadly neutralizing antibodies in response to COVID spike proteins while the human immune system does not.
That’s a bit interesting to the subject of COVID, isn’t it? Certainly more so than windmills and politics.
> To be fair, you are stigmatizing someone for offering a correct observation (that the successive COVID variants have proven less debilitating and deadly) and for asking a question that must be on many people’s minds: can monoclonal antibody administration promote resistance analogous to bacterial antibiotic resistance?
No, I am singling out another comment which spreads doubts and denial by hiding them among good faith arguments. For instance:
> (that the successive COVID variants have proven less debilitating and deadly)
Doesn't mean it's not debilitating and deadly.
> basically everyone I know has been infected now.
And I haven't and neither my best friend nor my parents did. But my brother did and another friend did. Guess which one is complaining 6 months later of symptoms that are not going away ?
> As well, rather than spending your mental energy developing excuses to dismiss, why not think on the subject at hand? You should wonder why this mouse model produces broadly neutralizing antibodies in response to COVID spike proteins while the human immune system does not.
> That’s a bit interesting to the subject of COVID, isn’t it? Certainly more so than windmills and politics.
I believe Covid was and is still dangerous and not to be taken lightly because "most people I know has been infected and successive strains are less deadly" (the last one being also dodgy since it might as well be less deadly for an individual but more deadly for a population if it infects much more people, anyway...). That's as worthy to discuss as the core of the submission is.
It is literally in the HN rules that you are supposed to assume good faith, not concoct false attributions of intent and conspiracy. I did not intend to hide anything, I was earnestly asking a question (clearly shared by plenty others in this post). It should not upset you this much. I apologize for anything triggering to you that I said, that wasn't my intent.
The question pertaining to the core of the submission does not upset me, nor do I find it in bad faith (that one I assume good faith since it's legitimate).
> Current Covid strains don’t seem all that bad, basically everyone I know has been infected now.
This, does. Because it has nothing to do with the submission but all with covid minmizing thrown in after a legitimate question.
What exactly does that tell you? I called you friend and apologized if I upset you (which you have acknowledged I did by comparing current strains to the original and making the judgement call that the current strains in our current situation aren't so bad... again relatively). I'm genuinely not sure what is wrong with any of that, perhaps a language barrier thing, apologies again in any case.
No, you did not simply ask that. You also said Covid is now not that bad and implied it's okay to be infected since everyone you know has been infected now.
If that is what you took from my comment I apologize that isn't what I intended to convey at all. I did however intend to ask a question about the topic at hand (broader vaccines) in our current situation which is categorically improved relative to early covid
In EU and US the majority of people have had covid and certainly nearly everyone has had covid or been vaccinated. The new strains are not as deadly as the original or the delta variant. That is factual.
"EU and US" is not even remotely approaching "universal": in total that is less that 10% of the world's population. Expand your horizons; this is not a parochial forum. For example, I was born in a country that is neither, and I live in another country that is neither.
Besides which, there are numerous EU member states whose vaccination rate remains below the population immunity level. More broadly, the global chain of infection, and the consequences thereof (preventable suffering and death), has not (yet) been interrupted by a sufficient global reservoir of acquired immunities.
Furthermore, "not as deadly" hardly corresponds to "don’t seem all that bad". Mustard gas is "not as deadly" as VX. Let's not move the goalposts. In the same vein, it would be a mistake to implicitly assume that future COVID variants will be less deadly.
Broadly speaking we don't have great data (in scale or quality) outside of the US and EU which is why I spoke to that. Things get pretty speculative even inside those borders.
> "not as deadly" hardly corresponds to "don’t seem all that bad".
That is a simply a judgement call really isn't it? We live with all sorts of terrible things. Cars kill over a million people each year and while terrible, they really aren't "all that bad"
I'm not trying to make light of something so serious only speaking in relative terms compared to what we've already been through. Also what is wrong with including vaccinated exactly? They have some level of immunity, that is what counts here right?
>you expressed a common fear that vaccination development becomes counter-productive
That is just false. I was asking if by developing such broad vaccines (as opposed to those that we have developed in the past) if we ran the risk of selecting for worse viruses. As best as I can tell the answer is no, but there isn't anything wrong with asking the question right?
> Cars kill over a million people each year and while terrible, they really aren't "all that bad"
I struggle to comprehend the mindset that allows anyone to think killing a million people "isn't all that bad".
> I was asking if by developing such broad vaccines (as opposed to those that we have developed in the past) if we ran the risk of selecting for worse viruses.
Whilst you were responding I edited that remark from my comment, since it does not lead to a worthwhile discussion. Nonetheless I'll stand by it as an appropriate characterization.
Things really can be good and bad. Cars I think by most accounts are good (do you disagree?), but they do lead to the deaths of a million+ every year, that is bad.
Junk foods like ice cream, pizza, soda etc. I think can be good but they also lead to the deaths of millions a year (albeit more indirectly). The world just isn't black and white. It is complex and there is nuance.
> I think can be good but they also lead to the deaths of millions a year
This discussion may as well end here, because I can have no meeting of minds with someone whose moral compass spins so freely as to wave away millions of human lives on frippery. The only other entity I've had a dialogue with willing to express a similar worldview was GPT-3. That AI was trained on a wide spectrum of human expression, so evidently someone out there agrees with such sentiment, but to me it's downright repugnant.
If conversations about COVID seem impossible it might be because a substantial portions of the population overestimates the danger from COVID by as much as 50x.
Can we please have this sort of research for the common cold and flu please. I hate flu season, I'm normally sick three of four times a winter. I get really sick at least once a year. I'd love to avoid that.
Unless you're licking buttons on the subway, how could you possibly be getting exposed to that many different strains?
For what it's worth adults get the flu about every 5 years[0]. It's not till we get elderly that we can start catching the same or similar strains more frequently.
Similarly with the cold, which are coronaviruses like COVID just lead to less lasting immunity.
Long story short. This kind of research won't help, give it several hundred years and the number of COVID variants will be similarly broad as cold and flus and people will catch them at a stable rate.
> Similarly with the cold, which are coronaviruses like COVID just lead to less lasting immunity.
This common knowledge needs to die.
"Well over 200 virus strains are implicated in causing the common cold, with rhinoviruses, coronaviruses, adenoviruses and enteroviruses being the most common."[0]
The quoted paper doesn't support what you say. It also doesn't demonstrate a difference in the elderly. Given that, I'm inclined to take the rest of this post with a grain of salt and I think every other reader should do the same.
Exactly this. People notice this when they have kids and kids start going to kindergarten.
I was almost never sick with colds until my kid started going out with other kids. I thought I had a great immunity, it happens I only had good hygiene - washing hands, avoiding contact, rarely going to mass event during flu season and etc.
As kids have poorer hygiene habits, are in very very close contact with each other they get sick easier. After a week or so the father is sick with exactly the same symptoms.
People keep saying this so there is probably something to it. I mean, not even the most optimistic mask studies show a long-term complete protection from all pathogens that can cause colds but okay, let's take it at face value: your wife is protected from colds because she wears N95s.
What this means is that your wife's immune system isn't getting challenged and isn't learning about the ever changing pathogens around it. It's not building immunity to the various strains every winter and it therefore can't get any cross-immunity ie against SARS-COV-2 [1].
All we know about the immune system suggests this is not good in the long term.
If true and I kind of hope it's not for this reason, your wife might be setting herself up for a very serious disease down the line. I hope this is not the case and wish both of you the best of luck.
Yeah it does. I made some changes when I got married. I think my problem is that I had my sinuses removed along with a tumor when I was a teenager. Now it seems I just need to see someone sick and I'll catch what they have.
During the pandemic I started taking vitamin d. That really took the edge off of the flu. I suspect I'm a bit low on that.
For what it’s worth, Vitamin D actually subdues your immune system in a lot of ways (and helps in others). One of the theories as to why low Vitamin D levels are correlated to higher deaths from COVID is that Vitamin D helps your immune system from going into overdrive.
I know this is might be a poor example but there are old anime series from 80s, early 90s where characters that get sick wear simple masks to protect others from spreading whatever they caught.
That's animated cartoon while in reality, whole pandemic I was observing the comments around the global and "local" Internet (as well real life convos) where people called the necessity of wearing masks as restriction of civil freedoms, and masks as "muzzles".
My sister was even harassed walking by street by some random guy who stopped his car, rolled window and ordered her to "take off this rag from face".
From what I've heard S. Koreans still prefer to wear masks despite that these aren't enforced in public space - tho, the particular places and situations where these are needed still apply.
So I wonder, do the countries that describe themselves as Western differ that much from Asia in term of public health and responsibility towards others, and just really basic hygiene? It doesn't seem to be a brainier to protect oneself and others.
Many asian women wear masks to avoid the sun. A tan is seen as unattractive so they'll put on a hat and wear a mask when they go out. At least my mother in law is like that.
I don't think this will ever happen. In my opinion the general cold / flu are just "normal" diseases indicative of low immunity. They're not so specific like covid, pox, etc. Though I'm not saying there won't exist medication with immediate effect (because common cold is fairly decent understood), but that there won't be a "one time" medication that will proof our entire lives from such things.
Unless you have some seriously and permanently weakened immunity, exposure to colds and flus actually helps long term. Also you are potentially passing this increased immunity to your offsprings.
Of course going through it sucks, I am in same bandwagon with 2 small kids and getting often sick with same stuff they have. And they do have stuff basically semi-constantly from mid autumn to mid spring. Half the class has constantly running noses.
How do you think kids build their immunity? You don't get it by just growing up, its exposure after exposure. Protecting them too much from common stuff is one of the worst things you can do as a parent, they will have serious health issues and allergies later on.
It normally means I recover about a week earlier when I get the flu. So instead of two weeks down it's a little under one. But I don't know for sure that's not just coincidence.
This can only help with the treatment of severe cases, which is not small success, but definitely not going to help get this pandemic over with! As far as I get it, you present the antigen and then it's up to your immune system to develop antibodies against it, and the antibodies from person A and from person B could B could be quite different, so, not sure, unless you get a shot of premade patented and expensive to produce antibodies, how this can help vaccine production.
The researchers have applied for patents on both the antibodies and the mouse model used to produce them. They hope to see their work developed commercially.
... followed by
This work was supported by the Howard Hughes Medical Institute, the Bill & Melinda Gates Foundation (INV-021989), the National institutes of Health (NIAID Consortia for HIV/AIDS Vaccine Development UM1-AI144371, P01 AI158571, Maximizing Investigators’ Research Award GM130386, Harvard Virology Program training grant T32 AI07245), Massachusetts Consortium on Pathogen Readiness (MassCPR) SARS-CoV-2 Variants Award, Emergent Ventures fast grant, FDA (MCMi grant #OCET 2021-1565 and Perinatal Health Center of Excellence project grant #GCBER005), the Danish Technical University and SANA, and IONIS.
[sarcasm]
Let me guess, $50,000 per dose MRNA vaccine that makes you immune to COVID, thanks for the grants suckers. [/sarcasm]
This is something that really annoys me (obviously) and I think it would make a lot of sense if "any patents arising from research done with monies given by <x> will confer on <x> a lifetime perpetual non-exclusive right to use and re-license said patent on what ever terms they deem acceptable."
It won't happen of course, but it should in my opinion.
Feel free to correct me if I'm wrong here but what I took away from all of the papers on the MRNA vaccines is that they were designed to tell cells to build a protein (spike protein) that would stimulate the immune system to create an antibody that recognized said protein and it was those antibodies that made it harder to become infected with SARS-COVID-2.
One of the papers I read compared and contrasted the antibody that Pfizer used in their development vs the one that Moderna used in their development, with the conclusion that the Moderna "provoked" antibody was slightly more effective at preventing an infection from taking hold.
And based on that understanding (which may be flawed, please let me know if it is) then having a better 'target' antibody that you are trying to provoke the immune system to create, would make an MRNA vaccine more effective.
I admittedly have no idea how it works, what the differences are but the article infers that the tech developed here can be used for vaccines. From the article:
“If it does,” he added, “it might provide a new therapeutic and also contribute to new vaccine strategies.”
Maybe you know, is this just for therapeutics and not vaccines?
Edit: looks like someone else answered this below....
Not saying it's impossible, but I've never heard of it happening in that direction[0]. The immune system uses natural selection to randomly generate and amplify successful antibodies. It seems that the likelihood of generating exactly that antibody in the immunization process is astronomically low.
[0] unless the lab-gnerated antibody is "seeing" a different part of the virus that the current vaccine doesn't see, in which case targeting the new spot in the virus is an obvious "next move".
> a lifetime perpetual non-exclusive right to use and re-license said patent on what ever terms they deem acceptable.
Probably the biggest immediate positive impact would be automatically securing the rights to produce and distribute the patented good in developing nations. BigCo isn’t making much money there anyway.
Economy of scale. You make little from a large population. Or you can go Nestle level evil and straight out exploit the most in need [1]. Plenty of ways for BigCo to make money of developing nations.
> Plenty of ways for BigCo to make money of developing nations.
Making some money sure, but developing nations are not great consumer markets and BigCo isn’t making a big chunk of its profit there. It ought to be possible for BigCo to be made to accept the loss of a market they probably would neglect anyway (especially pharma) in exchange for R&D funding to give legal clearance for other organizations to serve those populations.
You wrote: <<automatically securing the rights to produce and distribute the patented good in developing nations>>.
Real question for you and others: Where do we draw the line? That is an enormously complex question!
I have an equivalent to discuss: During the COVID-19 crisis, I was bothered that the South Africa gov't was pushing so hard to get access to produce vaccines locally without paying patent licensing costs. (Without very advanced pharma manuf facils, it would be useless. Many people under estimate the complexity of producing these new mRNA vaccines, let alone distributing them safely and correctly.) South Africa is, by many measures, a middle income economy. They could absolutely affort 10-20 USD per citizen to vaccinate their population -- not so different than what EU paid for vaccines. Please do not interpret this post as "dumping on SA"!. I just want to discuss a very specific example.
Related: The Serum Institute of India (which I think is the world's largest producer by vaccine doses) eventually secured a licenses to produce and sell vaccines. (Wiki tells me three were licensed [very impressive!]: AstraZeneca/Oxford, Novavax, and Russia's Gamaleya Sputnik V.) Does anyone know the details of SI's licensing agreements?
If their research is of something that is attractive to investors, no doubt they will. Grants are often used to fund research that does not attract investment for whatever reason.
Governments should not just fund drug and vaccine research. They should employ most of the researchers and own most of the labs. Problem solved. Give a hundred billion to vaccine research and then release it to the public with a mandated price - job complete.
One of the most interesting ideas I saw during the COVID-19 crisis about the balance of pharam research and distribution of new vaccines: What if the gov't guaranteed a price-per-vaccine and number of vaccines to be purchased if a new vaccine could be created? This is basically the scheme of Operation Warp Speed. The US gov't dumped tons of money into a few great ideas, then guaranteed to buy if they were approved by FDA. It stimulated massive parallel investment and created a few new vaccines in the shortest time in human history.
> Governments should not just fund drug and vaccine research. They should employ most of the researchers and own most of the labs. Problem solved. Give a hundred billion to vaccine research and then release it to the public with a mandated price - job complete.
That seems... a spectacularly naïve idea.
Governments could have done this for fifty years, but by and large they don't, because governments are generally capricious and short termist, and don't value R&D.
Actually governments used to do this. Universities being free and all. Yes companies can sell and distribute the products, but the government/universities retain the IP/patents.
Basically I’m saying they should make a finished solution but leave distribution and full scale manufacturing to private industry. Not because private will do that part better, but because at that point there’s not much need to use taxes to finish the job. What drug manufacturer wouldn’t want the contract to exclusively sell an already developed product? All they need to do is follow FDA regulations and pricing.
Either development is the tricky part, in which case it would be irrelevant if the formula is public, since another company won't be able to compete just by knowing the formula, they also have to fund development of their own; or the basic research is the problem, in which case development is a minor expense and should be covered by the sales.
Either way, making the results of research that has already been funded by charities, the state etc public should be mandatory, and would still leave these companies with plenty of profits.
Development is everything that goes into putting an application together for the FDA, as well as getting facilities together for their inspectors. It is indeed irrelevant if the “formula” is public. Every company needs to put together an application of some kind to make marketing claims. There are many kinds of applications.
> would still leave these companies with plenty of profits.
Development is undertaken with risk capital. “Plenty of profits” is not the bar; the returns must exceed those found elsewhere for the same level of risk. Otherwise new drugs are simply not developed.
The thread was about "why would Pfizer pay for R&D if the vaccine/antibody could then simply be relincesed".
And the answer is: because they can sell the vaccine for more money than it costs to research a new one.
If they have to pay extra to develop, then they still have a huge moat. Even if Moderna or J&J is also licensed to produce the same vaccine, Moderna will also have to pay the same cost before they can have a product, so no change in incentives compared to today.
This whole "but then who pays for development" is a red herring you've thrown in.
And in general, the bottom line is this: if a piece of research, be it basic research or clinical trials or anything else is mainly funded from public money, then it should belong to the public, not to the corporation that was payed to execute the study. The corporation has already gotten paid for the R&D in this scenario, so it's fair for the public to license that R&D to other corps as well, and allow all corps to compete on price of the finished good. If this research stops at the molecule, then let various corps compete on turning the same molecule into a finished product, and let them patent the finished drug, but not the molecule itself.
In small molecule the second player can just copy. With vaccines this is harder but a lot of the risk is already gone. Development encompases everything from tox, to dosing, and there is much risk at every step of the procees. For small molecule the lead is going to get massive amounts of small variations made and tested to try to find the one that works: that's not coming from the research that lead to a paper with a hit.
It's funny about that. I listened to an interview with Bourla where he said both that they need the patents for a return on investment/protect their IP and that it would take over a year for a competitor to scale up and release the product after they have released it so it's tricky.
You're going in circles. We were discussing a vaccine that was discovered with most funding coming from charities (B&M Gates foundation) or the state (NIH), and some by Pfizer. But, Pfizer gets to keep 100% of the results of this research.
Now, if by "development" you mean the cost of mass manufacturing and marketing the substance, then every company that wants to manufacture it can find their own, which will be payed for by, you know, sales.
Development means clinical testing, preparation and submission of applications for FDA approval, as well as design of production processes for new drugs.
They acquire the rights i don't think they fund much.
Why these diseases are serious enough to lock us all in our fucking homes but yet rampant profiteering is allowed is a travesty. The entire state and industry hand in hand, defacto fascism.
I've always been confused about the arbitrary lengths of patents. Surely for something like this, six months or a year is fine? Enough time to get to market and make a considerable size of buck, but brief enough that a much needed thing that is subsidised by public money can be used as widely as possible. (Remember, philanthropic funds are often treated favourably for tax, so are, in a way, also public-ish money)
On the other hand, you may have invented a novel type of hammock which is neat but has no social function, so, by all means have a quarter of a century of monopoly on that.
Actually patents themselves don't have arbitrary length. They are 20 years and then done[1]. That said, there are patents on refinements or add-ons that come later, and so sometimes the patent expires but it has been replaced by a new way that is even better.
There is a scheme in the pharmacy market for shifting patents to prevent generics from being produced, that scheme would be outlawed if we had the right mix of legislators in Congress (basically fewer people who are dependent on these pharmaceutical companies for campaign funds and PAC support). But the original patents do expire, the trick is convince folks that they don't do what they do as well as the new thing does what it does.See here[2] if you want the boring details.
[1] I've got a bit over a dozen patents that arose out of work I've done for others and ended up becoming very familiar with them, even get the occasional expert witness work when trolls need to be disabused.
The problem starts with the time between patent award and regulatory approval limiting the commercial exclusivity. This has driven big pharma to patent manufacturing processes instead of the compounds. If I understand it correctly from memory the Ritalin availability crisis was a example of process patent reengineering.
There is a system called supplementary protection certificates (SPCs) that gives an extension you the monopoly period to account for regulatory approval periods.
Drug patents have 20 years from the time of invention, but getting FDA approval takes 10 years after invention so that really only leaves you with a 10 year monopoly.
I think people are under the impression that the government is giving like 75% of the funding for drug development. It’s more like 1%. Getting FDA approval is a very arduous and expensive process. If you want to build an insulin factory, you’re looking at 8-10 years and $100 million to prove to the government that your insulin is safe to use. [1] That’s just for making generic insulin. Developing a new drug from scratch and getting it approved is orders of magnitude harder. A 6 month monopoly wouldn’t be close enough to recoup your costs.
I think it would make a lot of sense if "any patents arising from research done with monies given by <x> will confer on <x> a lifetime perpetual non-exclusive right to use and re-license said patent on what ever terms they deem acceptable."
If this were implemented, wouldn't it just be the case that no one would take your money?
Perhaps, I haven't been personally involved in a university lab looking for grant money so I don't know if they would turn down a grant if it required that any patentable work be also licensed to the grantor organization.
And to be clear, I don't expect this situation to change any time soon. Just annoyed by it.
That actually is a requirement with many DoD grants, in my experience. In general, such a clause would have to get additional approval from lawyers/grant admins at the university.
If you feel you have an understanding of the system I'm criticizing, why not help me understand why it has to be this way? I get it if you don't have the time or inclination to do so, but surprisingly I'm actually really open to learning new things and it would be appreciated not only by me but by other people reading your comments if you could explain the current system, perhaps other systems that have been tried and failed, and perhaps compare it with other systems (if they exist) that don't do it this way (giving the IP to the university even though it might be considered, by some less knowledgeable people, to be a 'work for hire.' Where it would seem that the agencies providing grants are doing the hiring.
I took an undergraduate course on the economics of science and technology. A large portion of it was devoted to patents.
The problem is generally that public funding accounts for extremely small amounts of the funding that it requires to take a drug to market. I didn't lookup any numbers for this, but I would guess it's very rarely above 1%.
The government could try to claim some share of the profits from drugs derived from research that was partially grant funded, but that seems logistically very difficult and not worth it. The government already gets a share through various taxes anyways.
The purpose of public research is to encourage innovation, which in turn benefits everyone. Private companies usually have no incentive to make any of their research public which can lead to many places repeating the same things.
I apologize if my statement was unclear. I'm not claiming to understand the system any better than you.
The type of comment that you left is a pattern I have been noticing where someone will state that they don't understand something and then proceed to criticize it.
This does not make sense to me, as I don't understand how someone can assume they have legitimate criticisms of a system without first asking clarifying questions to improve their understanding.
That's fair and I appreciate the feedback. FWIW, I suspect we think about the phrase 'legitimate criticism' a bit differently, I was trying to be pretty clear that my criticism, such as it was, was based on the existing system annoying me. For me, anyone who tells me about a system that annoys them I consider it a legitimate criticism in part because I think it is legitimate for anyone to criticize any system that annoys them for any reason. I may not agree with it, and the system may not annoy me, or I may sympathize but realize it is unavoidable, but it is still okay for them to criticize it.
well I don't really understand the system either, but there were multiple organizations making grants, so if you granted rights to all of them what rights would be left for you - that seems problematic. Also I suppose it was an expensive thing to do so they needed to get grants from multiple places, it seems like any recommendation to change this would be liable to have all sorts of side effects and, in the short term at least (5-10 years) likely to make the system function worse than it is now.
Perhaps there is some negotiation already going on for grant moneys, I would expect so if any grants were sizable, I mean if I am giving you a million dollars to study something I might say before hand these are my requirements and you would probably say yes or no, but maybe some grants were much less in size and involved things like use of facilities. In those cases it would be much more likely to change your value estimation of the grant and maybe refuse because not worth it, but if not worth it less stuff gets made and at some point we are the things working worse than before because some researchers would be like screw this academic career I can just go be a quant somewhere.
I mean as I understand it being a scientist is not exactly really rewarding https://www.zippia.com/scientist-jobs/salary/ so I would probably not want to do anything that made it potentially less (financially) rewarding because while people also do things for the good of humanity and so forth at some point when you're eating your Top Ramen with your disgusting room-mates maybe you might be tempted to change your life course for something with increased comfort.
The government (or other non-profit entities) funded significantly more than 0.01% in this case. You’re not wrong that there’s still a ton of money required to get from “this works in a lab” to “this is something available at your local pharmacy”, but it’s not 4 orders of magnitude more…
That’s also discounting the fact that they aren’t paying for all the projects that don’t make it to the “works in a lab” stage. That a significant chunk of risk that they aren’t exposed to.
You can just look at the budget of the NIH versus private and corporate investment in drug development. What the government spends is a fraction of what private companies invest.
To get a drug approved you're looking at $5k-$15k/person/year in a Phase 3 trial (depending on the monitoring needed). You can call up an CRO and ask for a quote. I did this several jobs ago.
Just to give you a sense, the Pfizer Covid-19 vaccine was 47,000 patients [1]. These patients were followed for 2 years. For a rough estimate, that's $5,000 x 47,000 x 2 years = $470M.
Half a billion dollars, just for one clinical trial.
That's already 3 orders of magnitude larger than a typical $500,000 grant for basic lab research like this paper.
And that's just the clinical trials. It doesn't include the trials leading up to the pivotal trial, the manufacturing development costs, the health authority submissions costs across 130 countries, etc. Then add on top the cost to make the actual drug and put it in a vial and ship it around the world.
And sure, "they aren’t paying for all the projects that don’t make it to the “works in a lab” stage". But conversely, the government never bears the risk for later development that fails. I remember Pfizer a couple decades ago spent $1B on a new manufacturing plant for a drug that never got approved.
How would this work as a vaccine? I understand there are antibody therapeutics which inject specific antibodies into your system to help fight off COVID, but do those antibodies last and reproduce? Something else?
I was under the impression that we can mutate it into a corner because there are only so many shapes it can mutate into before it doesn't work and the virus can't get into cells.
I'm not sure about that. There are probably hundreds or thousands of still-viable mutations it might come up with at random, and we don't want to inject dozens of vaccine candidates to deal with them. Or maybe we do? A lot of adults have probably had a dozen or two dozen varying flu shots.
It's not like the virus waits until we start hitting it with a vaccine, and then mutates in response.
There's a certain amount of variation in the population. More fit genes are more common.
If there's other variations of this portion of the spike protein out there, they're almost certainly less fit than the overwhelmingly predominant type. Maybe if the predominant type is severely attenuated by vaccine these will get more chance to replicate and become a bit fitter, but there's no guarantee they climb up to parity with the "old design".
If absolutely no other variations of this part of the spike exist then the antibody could remain effective and our use of it wouldn't materially push the virus to mutate.
But, if any (survivable) variations do exist, their survival advantage would grow tremendously once this antibody saw widespread use in treatments, which would lead to the variations likely becoming dominant quite rapidly thereafter.
Still, there's no reason not to keep searching and studying. We may be able to make an effective treatment based on this.
True, but it also works the other way, the variations that are currently less successful but have a mutation that avoids this antibody may be more virulent.
But aren't those still-viable mutations all relatively close to the existing ones which means that existing vaccines will work against it?
Like I was under the impression that there were relatively few novel configurations that it could evolve into which would evade vaccines, meaning that in theory a couple rounds of vaccines would be enough to beat it.
It is possible that we might be able to back it into an evolutionary corner, but we don't really know enough to know which "directions" lead to dead-ends and which ones lead closer to a leap into a novel and more virulent pathogen.
Antibody treatments are apparently a whack a mole game where they're constantly getting out of date and ineffective as we allow the virus to keep spreading and mutating.
We don't allow anything. The writing was on the wall in March 2020: back then it was already too late to contain it. Omicron just sped up the rate at which it is infecting people.
I'm going to wait for actual careful human testing .... could be that 5% of the human (but not mouse) population have a variant of some critical metabolic path that this anti-body attacks .....
You are not an expert and have only anecdotal evidence. Someone might read your post and assume that your advice is healthy to follow, while it flies in the face of actual medical advice. As such, your post is actively harmful to other people.
It is also not intellectually interesting, as it is just a rehash of what is essentially facebook COVID reporting.
At the very least you should not try to infect others with your harmful information. It is very antisocial to do so.
Never said I was an expert, and I was the one who labeled my story anecdotal before you did.
What advice did I give? I said, " If you don't have natural immunity, yes, some vaccine is recommended".
My whole family came down with COVID at once. I am not jabbing my young, healthy children with an experimental mRNA virus with no long-term studies available given it has only been in circulation for less than 2 years. Tell me why I should if you think you know better. If their health got them through an initial infection without any complications, why shouldn't I think their health and the fact they now have antibodies, and a deeper B and T-cell memory of the virus, is sufficient?
I am not on FB, so I don't know what you mean "essentially facebook COVID reporting."
Here's just one medical paper citing long-Term persistence of antibodies in people who had SARS in 2003-4. Do your own searches on 2003 SARS-CoV and SARS-CoV-2. You'll find more than enough to say it's legit, and not FB reporting.
Here are some papers about persistence of antibodies, or immunity in the form of B and T-cell immunity in SARS-COV-2 or COVID-19 subjects:
The CDC, the so-called experts, have been wrong so many times on COVID I have lost count. They ignored natural immunity throughout the entire epidemic. I still test over 15 in an IgG antibody test (over 15 is considered a positive in the test). Last test result was 113 a whole year after infection.
I said I didn't trust that the persistence of the mRNA and spike protein was temporary after vaccination. The CDC had up on its site that the mRNA and spike protein did leave the body shortly after vaccination. How come they deleted that statement from their current page? Check the archives to see it before they deleted it. They didn't note why this important point was quietly removed so we could understand the edit. I can only assume it was proven incorrect, which is astonishing, since there were studies in Japan about biodistribution that should have raised the call for more studies, but instead it was buried or stigmatized as anti-science. Anti-science is deciding not to test if a hypothesis is true or false, and just ignoring it.
SAR-CoV 2003 infected individuals still test positive for antibodies 19 years after. I know it's not the exact same virus as COVID-19, but nonetheless it is a coronavirus and natural immunity is persistent. Also natural immunity is based on being exposed to the whole virus, not a select set of the spike proteins. I'll go with natural immunity on this one; I'm not advising people seek to get COVID, but if you have, your choice to vaccinate should be based on this as a factor along with your age, health, and doctor's advice.
Covid antibodies, even vaccine induced ones, don't stick around for much more than 3-6 months. Whatever natural immunity you got nearly 3 years ago is long since useless. You're either getting lucky or an asymptomatic case and not knowing it.
edit: Since you're unvaccinated, go get a covid antibody test and check for yourself how good (or terrible) your immunity is to the virus. You can take either one, the S type or N type test, since you won't get a false positive from vaccine antibodies. Put your money where your mouth is and find out exactly how little protection natural immunity from 3 years ago is providing you.
> Whatever natural immunity you got nearly 3 years ago is long since useless
This is factually incorrect. You don't have perhaps protection against infection, nor probably symptomatic disease, but there is working natural immunity, in the form of immune memory and cell based immunity (T lymphocytes).
That is far, far more resistant to variants than humoral (antibody based) immunity, mainly because only antibodies neutralizing the S protein are able to prevent infection (so more vulnerable to mutations).
Cell based immunity can't prevent infection, and can not necessarily prevent disease (as in, having fever, cough...), but it is very effective in dampening the effect of infection (either through recruitment of other immune cells, or by killing infected cells). Memory T and B cells generally last quite a lot of years (and with SARS-CoV-2, up to two years at least), so this memory is long-lasting.
Where is the T cell immunity? People are on their fourth and fifth infections now. If there were strong T cell protection we wouldn't see constant reinfection.
T cells will save us has been a big coping strategy from people trying to claim the pandemic is over too soon. Hucksters like Monica Ghandi have been saying T cells will save us for years now.
When... when will it happen I ask. Over a million dead bodies and people still racking up infections. Back up to an average of 500 people dying a day even in our summer lull right now, and it's climbing again.
Look at the entire continent of Africa. A high seroprevalence of SARS-COV-2 antibodies, and yet these mostly underdeveloped nations have a much lower death rate even if you count excess deaths due to poor reporting than the US with supposedly all the best to fight it. My thought is that statistically Africans are thinner and get outdoors more than their obese, diabetic, and hypertension-suffering peers in the US and Europe sitting on their couches. I tested 113 a full year after my COVID-19 infection on an IgG test when 15 or over is considered a positive antibody test. I am going to get tested again when I return from Saudi back to the US a full two years after my infection. I bet I am still in the 80s or thereabouts. And I have not had a second infection. I am fit, do not suffer from hypertension or diabetes, and I had COVID. These are solid, scientific factors that put me in a lower risk category even if I get COVID again.
See my response above, however, to your edit remark: a full year later I tested 115 (15 is a positive for IgG test). I referenced studies for both SARS-CoV-1 in 2003 and COVID-19 where antibodies are detected much further out than your 3-6 months. They are still testing positive for antibodies to SARS-CoV-1 (2003), 19 years later.
To your "lucky" point, I can't qualify that. If I have an asymptomatic case, that tells me my natural immunity must be pretty good, given my multi-vaccinated colleagues, at least three of them, have lost work due to second and third infections. They had the vaccination before getting COVID, so I wonder if they have weak immune systems, or the vaccine somehow is not as good as natural immunity. The CDC finally admitted natural immunity was as good or better after a year of ignoring natural immunity, and after they pushed it on healthy children, and Pfizer makes tens of billions of dollars with every booster or new series of vaccines.
I truly believe in the next 5 years it will become more clear that the majority of people who suffered from COVID that were under 55 years old was because of obesity, diabetes, and hypertension, or other immune-compromised patients. The numbers are already in the CDC datasets and other datasets from around the world showing this trend. Everyone has a horror story of a young, healthy person who died, however it is the thin tail of the distribution, and not the norm, and it is a very statistically insignificant number to push a one-size fits all mandate to vaccinate.
The last two comments you've posted (this and https://news.ycombinator.com/item?id=32473246) have broken the site guidelines egregiously. Can you please stop doing that—regardless of how bad another comment is or you feel it is? We ban accounts that post like this and I don't want to have to ban you.
(I suppose I'd better add that no, I'm not posting this because I agree with the GP. I'm posting this because I saw a repeated pattern in your comments.)
