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Spread of Delta variant driven by both immune escape and increased infectivity (cam.ac.uk)
42 points by thunderbong on Sept 8, 2021 | hide | past | favorite | 109 comments


https://www.frontiersin.org/articles/10.3389/fimmu.2020.6113... This explains why we need to develop a vaccine that provides mucosal immunity to defeat COVID.


> “The team found that the Delta variant virus was 5.7-fold less sensitive to the sera from previously-infected individuals, and as much as eight-fold less sensitive to vaccine sera”

I read this as “natural immunity is better”. Unless I’m reading that wrong, why don’t we hear more about this? I’m vaccinated AND got a breakthrough infection and I’m worried that my immunity is weaker than that of my wife who was unvaccinated but recovered.


Natural immunity is 13 times stronger than what we get from the vaccines, according to data from Israel.

https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...

We probably didn’t even need to waste vaccines on people who had already recovered.


I agree with your last statement, but that is 20/20 hindsight.

The media played up reinfections tremendously last year and even though there was no data, I think it impacted politicians/public health policy makers to err on the side of caution.

The interesting thing is the vaccine was never tested in previously infected individuals and that could have been a contraindication for vaccination.


As a horror writer I cannot help but imagine moralizing scenarios where in the west, we vaccinate and lockdown and hoard vaccine and have immunity from vaccines, while in the Global South and places forced to reach herd immunity are realized to be immune to all variants while we must race to make and inject ourselves with boosters against each new variant. A variant arrives that is even more deadly and it wipes us out while the Global South survives better and ascends. I'm always writing stories!


> I’m worried that my immunity is weaker

It is my understanding the effect is additive. The vaccine shows your immune system a small but important part of the virus so your immune system knows to respond to those particular proteins in the future. A natural infection exposes you to more proteins, so your body also recognizes those as dangerous.


From what I have learned over the past months wrt variants and vaccine efficacy, the delta variant has a mutated spike protein which allows it to more easily and I believe more quickly bind to host cells and begin inserting its genetic information.

I understand that the spike protein is the most saturated target of the known immunological study, vaccines have been mainly targeting this protein. Normal immunity works on the current variant of infection and will react to these mutations.

As an aside, the protein is very interesting, check out this[0] linked animation of the viral insertion, note the dramatic conformal changes.

The mutations in particular variants might achieve a little bit of infection speed, and a little immunological camouflage, both seem to support allowing faster replication.

I don't know because I am not a doctor or virologist, but I would conjecture that the vaccine still prepares our immune responses to target this kind of protein, so it can somewhat more easily learn the new signature and produce antibodies.

[0] length: 01:54 title: Animation of SARS-CoV-2 entry into human host-cell - https://www.youtube.com/watch?v=Xuc9D4LVJdg


You're fine, you got a complimentary booster shot early. On average the best immunity is recovered and vaccinated one way or the other, so you may be better off than your wife now. Vaccine breakthroughs were expected so there's nothing wrong with you.


Dumb people are going to want to go to covid parties to get infected naturally because it is better immunity..

Public health messages need to be kept simple.

Natural immunity should be better because you are exposed to all the same proteins in the vaccine plus more and also possibly for a longer period of time and at a higher quantity.

Now that you had delta, you should be immune to delta and partially immune to whatever delta mutates into.


> Dumb people are going to want to go to covid parties

When I was a child, parents would inform other parents when a child had chickenpox; so they could have a sleepover. That was normal practice in the portion of the USA I grew up in. As a result, nearly everyone my age has natural immunity to chickenpox.

I share that anecdote to point out that the idea of an "infection party" is a really old idea that was practiced at scale. It's not unreasonable to assume people will treat this the same way based on that type of past behavior. Whether it's "dumb" or not remains to be seen.

Edit: I wanted to add for younger persons a blurb about WHY you want to get chickenpox as a kid. Children experience mild symptoms from chickenpox - it's a non-event other than missing some school and having a few sores. Adult cases of chicken pox however are fatal by a large majority.


Adult cases are not fatal by a large majority. The highest number I could find said that adults were 25 times more likely to die from chickenpox than children.

I found a death rate of 21 per 100000 adult cases. That's not a majority. [0]

Also, it's better to never get chickenpox at all, as shingles is very painful. Shingles is the reactivation of the chickenpox virus. If you've ever had chickenpox, you are at risk of shingles.

[0]: https://www.cdc.gov/vaccines/pubs/pinkbook/varicella.html


Now in 2021 we are going to force kids to interact with their peers with a facemask on to make sure they never get to build a competent immune system.


I’m with you on this. I think kids getting it is the key to us getting out of the cycle.

Despite media hysteria, the risk to children is extremely low. So low that the UK isn’t going to vaccinate most kids at all.

https://www.newsweek.com/uk-wont-vaccinate-most-children-tee...


Please do explain exactly how will kids get us out of the cycle?


They'll develop robust natural immunity with negligible risk, then grow up and become adults with robust natural immunity.


I think your logic is wrong.


There's still kids eating and playing in the dirt and there's still outside of school interactions going on. Plenty of kids not washing hands.

Wearing masks in school reduces the severity of an outbreak so that hospitals do not get overwhelmed. After all kids can get vaccinated that will help reduce hospitalizations too.


Right - but now there's a chickenpox vaccine, so you don't need to subject kids to the misery that is an actual case of chickenpox or to the rare outcomes where it's fatal or permanently disfiguring.

How fortunate are we now that within two years of Covid emerging, we have a similar vaccine that can prevent nearly all the suffering?


chickenpox has a death rate of .001%

Covid has a death rate of .5% (higher for older people, lower for younger)

flu has a death rate of .1% and you dont see people having flu parties..


> Covid has a death rate of .5% (higher for older people, lower for younger)

That is a very bold statement, given that mild cases are less likely to be recorded in official data sets, affecting the denominator much more for younger people than older people.

What we do know is that a total of 412 people between the ages 0-17 are known to have died from Covid19 in the U.S. since January 1, 2020. Total deaths from all causes in that age group was 55,352 for the same period and the total number of Covid19 deaths in the U.S. for the same period was 643,858. Out of that 502,863 were among those older than 65 years of age.

If we take your claimed death rate of 0.5% at face value, 412 deaths implies 82,400 infections. According to the U.S. Census Bureau[2], there are about 74 million people under the age of 18 in the U.S.

So, the assumption of 0.5% IFR implies that only 0.11% of those under the age of 18 got infected with Covid19 in the same time period.

Therefore, either the 0.5% IFR overestimates the actual IFR by about 500-600%, or Covid19 is just not that infectious among those younger than 18.

I am going to with the assumption that 0.5% IFR is way too high. In that case, it makes absolute sense not to disrupt the lives of young children to the extent we have already disrupted and allow them to gain natural immunity through each wave.

[1]: https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-by-Sex...

[2]: https://www.census.gov/quickfacts/fact/table/US/PST045219


I agree the death rate for children under 12 is probably very low. It could be as low as .01%.

I specifically wrote the rate is lower for younger people.

We will get a better idea of the death rate in children under 12 this year. As far as I know it is still holding very low.


> I specifically wrote the rate is lower for younger people.

Exactly. The question is how much lower. If, as it seems, it is low enough compared to all the other things that might harm a child, it would be rational to introduce them to the actual virus early and often.


Same has been common in other parts of the world.


> Public health messages need to be kept simple.

By simple you mean, dishonest?

People aren't as dumb as our betters believe. They pick up on obvious lies ("stop buying masks" => "everyone must wear a mask"), dishonesty ("ivermectin is for animals") and inconsistencies that fly in the face of intuition ("even if you had covid you still need the vaccination").

If the powers that be would stop trying to "shape human behavior" through lying we wouldn't see nearly the same level of vaccine hesitance and alternative medicine we do right now.


I agree that the public health messaging has quite a number of statements that may not be true. But they may not be false either. Instead of lies, scientists are erring on the side of caution for what they do know.

I agree that sanctimonious public health and politicians have created a lot of distrust. Their messaging is condescending, manipulative, and generates the direct opposite of what they are trying to achieve.


There can be honesty even if they are playing it safe: Just state plainly that the data is inconclusive, things are moving quickly and this is the best estimation they currently have. Spewing out patronizing misinformation (see the FDA's sassy "You are not a horse" tweet) is counter-productive.


And this is exactly the kind of reasoning that leads smart people to distrust public health messages.


"Public health messages need to be kept simple." is something I almost agree with. The problem comes is when the simplicity starts leaving things out and edges into "not the full truth," at which point people can identify that you have -- perhaps not intentionally -- deceived them. That lowers trust.

This current pandemic is an excellent example of what happens when you have lowered trust.


> Dumb people

How did we get to the point where we have to act like other humans are mentally inferior/incapable just for experiencing reality in their own unique way if it differs from our own?

e: me irl https://i.imgur.com/is5pp8k.gif


in the olden days dumb people just died and didnt reproduce. We have overcome a lot of natural selection so there are likely many more dumb people than in the past.

We all share the same reality that you have a .5% chance of dying from covid. If you choose not to take lifesaving vaccinations then you are dumb, especially if you are in a high risk category where the risk of death is 1-5%

Im not at all in favor of mandatory vaccinations.


> olden days dumb people just died and didnt reproduce.

It seems like this is not an internally consistent statement.

If "dumbness" is genetic and smart people make smart offspring and dumb people make dumb offspring, where do today's dumb people come from? Clearly, not the dumb people who died and did not reproduce.

The correct statement is that people who were not well adapted to their environment died. Some of them actually died after reproducing.

> same reality that you have a .5% chance of dying from covid.

One, "known" averages and individualized "probabilities" are different things.

Two, see https://news.ycombinator.com/item?id=28460412

Now you are confounding the probability of a random infected person dying with the probability of a randomly picked person in your own demographic group dying from Covid19.

For example, 3,145 females between 30-39 years of age died from Covid19 between 01/01/2020-09/04/2021. It looks like there are about 22 million people in that age group which corresponds to 0.014% probability of a randomly picked person in that group dying from Covid19 within that period.

[1]: https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-by-Sex...


Why do we have to be so mean about it though? All the ableist language we throw around really saddens me https://campbellmgold.co.uk/archive_esoteric/morons_imbecile...


I think it is because we have a political structure that people to be increasingly accountable to the choices of others responsible for their mistakes. It breeds resentment and hatred.

Absent this structure, people would have no problem with an idiot making mistakes. Take that same person and make others pay for every mistake they make, and guess how people will respond.


> Natural immunity should be better because you are exposed to all the same proteins in the vaccine plus more

This directly contradicts what immunologists seem to be finding as in the "Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection" [1] study.

Summarized by the director of the NIH [2]:

> antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.

If there's one thing we should learn from this pandemic it seems like the complexity and non-intuitiveness of the immune system is amongst them.

1: https://pubmed.ncbi.nlm.nih.gov/34103407/

2: https://directorsblog.nih.gov/2021/06/22/how-immunity-genera...


Early epidemiology is showing better immunity from natural infection.

A receptor binding domain is the place the on the virus that the virus uses to bind to cells.

However antibodies can bind to any part of the virus causing the virus particles to be attacked by the immune system. It is good to bind to the receptor binding domain, but it is good to bind to other parts of the virus too.

As the virus mutates, having antibodies that react to as much of the virus as possible is better than only having antibodies targeted towards the RBD


Preliminary data from Israel suggests that immunity acquired through natural infection may be more robust to variants like delta, compared to vaccine induced immunity. See this preprint and discussion from a couple weeks ago [1].

[1] https://news.ycombinator.com/item?id=28307224


That's kind of beside the point. With natural infection, the risk of severe illness is also much higher. So for most people trying to get "better" immunity by natural infection is not a good tradeoff. It's kind of like saying that since it's extremely rare to get bitten by a shark twice, you should try to get a shark to bite you once in order to acquire "immunity" to sharks.


A lot of vaccine hesitancy (in the US at least) is driven by refusal to acknowledge natural immunity. Ignoring it is another "noblie lie" to help drive up vaccine numbers. It's much easier to say "just get the vaccine".

However, it's a massive ethical violation if the vaccine provides no improvement over natural immunity. It's still pretty bad if it only provides minimal improvement. "Just get the vaccine" would be an ok policy if there was a 0% chance of negative effects from the vaccine, but that is not true.


Ive suspected all along the massive media push that "natural infection only generates immunity for 90 days" or "6 months" or whatever would turn out to be false. The media played up anecdotes of reinfections but there was never any actual data.

The thing is they never lied. At the time they made those statements the virus had only been studied for that long.

By the time the vaccines were created the "reinfection" idea was entrenched (even though not proven) and the vaccine was recommended just in case.


I think far more vaccine hesitancy in the US is driven by glorifying "natural immunity", especially when it's not clearly stated whether it's pre- or post-COVID immunity that's being touted. For example, I can't tell from your comment whether your position is that people shouldn't get vaccinated at all or whether they shouldn't do so if they've already had COVID. The latter position is debatable, but the former would be firmly contrary to pretty much all known scientific evidence (as long as we're talking about the general population and not a specific subgroup).


What kind of decisions would you make with that information?

If you got the vaccine and then got the disease, be happy, you've just acquired natural immunity on the easy way.


I think the reason why it's so easy to spread misinformation (not just about COVID vaccines) is that there's just too many facts out there. It's easy to cherry pick facts without context to support any conclusion whatsoever. Another comment in this thread points out that vaccination typically gives 10,000-100,000 times the antibody needed to fight an infection. So the 5.7-fold vs 8-fold difference is fairly meaningless in the proper context, but it can create doubts wholly disproportionate to its significance.


"Natural immunity is better" is a very misleading and dangerous statement. Many people take it to mean that their natural immunity is better even if they have never had a covid infection before. Many people, including young and recently healthy people are currently painfully and tragically dying in overcrowded hospitals because they believed that. Some especially misguided people have tried to get the virus intentionally so that they can get this much ballyhooed "natural immunity". The results have been predictably disastrous.

Yes, once you have had the virus and are lucky enough to survive and recover, the natural immunity thus obtained is better. For several months. Then after about 6-9 months (afaik, check the cdc site for the exact period) your natural immunity wears out and you are better off getting a vaccine. But if you haven't had the virus, your natural immunity is not very good at protecting against it (that is why millions of people around the world have already died), and it is a very dangerous risk to take.

My cousin had covid and long covid after it. She got covid before vaccines were available. She got the vaccine as soon as recommended by doctors for people that have suffered from covid. She really did not want to repeat that experience.

States whose politicians have been talking up natural immunity are very hard hit. Hospitals throughout the south are overcrowded. There is a country wide shortage of oxygen, which may soon start resulting in more deaths. This is a very bad time to to talk up misleading notions of "natural immunity."


> it takes eight times as many antibodies from a vaccinated individual to block the virus

If this is the case, then how can we explain how vaccinated individuals experience less severe symptoms and fewer deaths? Is it because once vaccinated, the immune system is able to respond to this 8x higher demand?


Every article that leads with this kind of stat is guilty of lying by omission. The typical immune response produces 10,000-100,000 times more antibodies than “necessary” to fight an infection.

If delta needs 8x more antibodies, then, well, our immune response is only overkill by a factor of 1,250-12,500.

Perhaps that’s enough for some of the virus to escape. But it’s still plenty to prevent severe illness!

Of course, these are just averages, and the 8x number does mean that people who have a depressed immune response are more likely to just not have enough antibody production, though the relationship between “8x” and this response is complex.

And in reality, transmission is driven in part by how much viral replication happens before antibodies are generated in large numbers. Delta is also better at this, presumably.


I'm open minded to what you're saying but help me understand how both this

> The typical immune response produces 10,000-100,000 times more antibodies than “necessary” to fight an infection.

can be true, and how vaccines are basically 90% effective at preventing symptomatic illness (kinda sorta, leaning towards the high end.)

Feels like the numbers don't match up.


The short answer to your question is that it takes time to mount an antibody response.

Vaccines do one big thing: they "teach" the adaptive immune system how to produce antibodies for the virus, and in the process the body produces a ton of antibodies, which fade over time. The antibodies fade quickly-ish (months), the "learning how to make antibodies" fades much more slowly, if at all (decades).

1) You get symptoms if you don't have enough antibodies in the right place when the infection comes in. 2) You avoid severe illness if your body can produces enough new antibodies (if it doesn't have enough) fast enough before the virus infects the really vulnerable parts of you.

People who have symptomatic breakthrough infections probably didn't have enough antibodies left in their noses to counter the initial infection, but are able to very rapidly mount a new antibody response so they don't get sicker. The initial 100,000x overkill is full-body, and fades over time. Months later, a vaccinated person might not have enough antibodies floating around in their nose to completely neutralize an airborne bubble with 10,000 virus on it landing inside.

As someone else implied elsewhere, the immune system is super complex. I'm going to attempt an ELI15 here. Apologies in advance for the wall of text.

== A Story ==

There are two parts to the immune response, called "innate" and "adaptive".

The innate response are first responders. They kick in as soon as they notice the "wrong" thing floating around in your nose/airway/lung cells. This response produces the early symptoms associated with respiratory infections: inflammation, sneezes, coughs, sore throats, runny noses, fevers, etc. It's trying to get as many of the body's white blood cells (immune cells) into the area as possible to clear out this virus that is simultaneously infecting cells and reproducing like crazy: doubling every 20 minutes; by the time the innate system kicks in, your hijacked airway cells have probably produced millions of new virus already. The more virus, the stronger the innate response: more immune cells, more killing infected cells, more clearing of cellular debris, etc. Your nose is runny, your throat is inflamed, etc. -- it's a huge battle, with millions of your cells fighting billions of virus. The best they can do is try to stem the tide, and they very likely won't win on their own.

Fortunately for you, during all this, some of your cells take parts of the virus, and present it to the cells responsible for the adaptive immune response. These are the scientists sitting in the back lab figuring out how to produce "antibodies" -- these are the red shells in MarioKart. They are designed specifically to latch on to and inactivate the invading virus, and make it super easy for the rest of the immune cells in your body to recognize the virus as foreign and destroy it. Designing these antibodies takes some time, unfortunately, and meanwhile there's a huge battle going on for your airways. Antibodies are HARD to design: you want something that attacks ONLY the virus, and not, say, also your pancreas by accident, because then you get Type 1 diabetes, and, well, that's not so great.

There is a lot of time pressure, because the virus is winning, and if the back lab scientists have never seen anything like this virus before, designing the antibodies can take days, maybe even a week or more, and then producing them in mass quantities takes days longer. The virus could overwhelm the body in the meantime.

BUT! But, if your adaptive immune system's scientists have seen the virus before, say because you were vaccinated -- a process in which your immune system was presented with a bunch of parts of virus that were taken to the back lab and the scientists designed antibodies for it, WITHOUT the time pressure of an actual infection -- then they basically have blueprints ready to go. (Less time spent coming up with plans means less time for the virus to overwhelm you.)

Now, regardless of where your adaptive immunity learned to make antibodies, when your body is ready, it goes to TOWN: we are talking trillions of antibodies produced in days, they literally flood your whole body. At peak there could be hundreds of thousands of antibodies for every virus particle. At this point, unless the virus figures out a way to hide from antibodies, it has more or less no chance. It's over. You've won. Your body will still need to clear the battlefield, so you may still have symptoms for a bit while this happens.

For vaccinated folks, there may even still be antibodies floating around from the vaccine, making everything much easier. There may be so many antibodies floating around that the virus doesn't even stand a chance -- it gets neutralized really fast (and transmission is blocked); there may just be a few antibodies around, but the adaptive response kicks in fast (mild symptomatic illness) and wipes the floor a few days later.

I hope this helps paint the big picture (with timelines) of what happens when a virus lands in your nose. I'm sure the HN crowd can imagine all sorts of edge cases here, and when hundreds of millions of people are infected with a single virus, basically any edge case with probability greater than 1e-6 is going to happen >100 times.


Both can be true if ~10% of the population do not have a "typical immune response" to the vaccine. This can be due to a number of factors such as age, preexisting conditions, general health, etc. Plus the immunity from vaccination "wears off" over time, and some of the earliest recipients are now 8+ months post vaccination.


That's really interesting, thanks.


The problem is that the immune system is an incredibly complex and dynamical system that almost nobody with only a general biology understanding is equipped to understand. It's even worse if you have no familiarity with biology.

Your general bio classes in college gloss over immunology to a point that it's practically a misshapen lie. (Not unlike undergraduate general chemistry.)

You have to read and study a lot more to understand and describe the behavior of the system such as the parent poster did. And that's just one small detail in an elaborate series of interacting mechanisms.

It's so weird to see the world impacted by something people are ill equipped to understand. And it makes you wonder about all the other crises we deal with where you have absolutely zero bearing for understanding.


In this case, I don't think it's necessary to go into too much detail about how the immune system works. The issue is that if you are going to _some_ level of detail, then you need to include all the relevant context. In this case, the number of antibodies that the immune system can produce goes along way to explain the points made in the rest of the article.

PS I am aware how damn complex the immune system is and how complicated it can be to explain to people at the right level of detail. I once attempted to watch a lecture on how the spike protein and antibodies work which went into detail on all the chemical reactions that occur at each step and it is just insane how much complexity there is to it. And that was presumably a simplification of what actually happens.


This is in comparison to the Alpha variant. Better quote:

>compared with the Alpha variant - in other words, it takes eight times as many antibodies from a vaccinated individual to block the virus.

Needing 8 times the antibodies int a problem if you have anitbodies to spare. Most vaccinated people do, but not all, depending on their immune system, exposure level, and vaccine reaction. This is why we see only slightly lower efficacy for the vaccine against Delta vs Alpha, not an 8X reduction in efficacy.


The specific part you excerpted, by itself, is confusing. When I read just your comment, having not read the article, I interpreted it as:

"it takes eight times as many antibodies from a vaccinated individual to block the virus [compared to an unvaccinated individual]"

When I went to find the excerpt within the article, I realized in context it meant:

"it takes eight times as many antibodies from a vaccinated individual to block the [delta variant] virus [compared to blocking the alpha virus]"

And separately offers the information that for antibodies from natural immunity, the difficulty jump from alpha to delta is 5.7x instead of 8x. Which would suggest that having natural immunity could be better than having only vaccine immunity, but definitely doesn't suggest that being unvaccinated is better than being vaccinated. So there's no mystery for vaccinated individuals having better odds against COVID than unvaccinated ones.


It does not necessarily mean that virus is 8 times more effective in the general case, just that it takes more resources to battle it.


The current vaccines only provide systemic immunity but fail to provide mucosal immunity. Until they come up with a nasal vaccine plus the shots we will not stop COVID-19 as vaccinated people can still act as vectors of transmission.


The virus is here to stay, vaccines or no vaccines. We need to learn to treat it effectively or accept vaccine boosters every 6 months


I'm fine with vaccine boosters every six months. Please! Sign me up!


Me too but I am old.


[flagged]


The virus mutates quickly so the vaccine can't be expected to be as effective at new variants compared to the variants it was designed to combat.


If thats true why the boosters? Or are you claiming the boosters have been upgraded with latest variants?


> Or are you claiming the boosters have been upgraded with latest variants?

Ok, what would YOU do if you ran Pfizer or Moderna?

1. ship v1.0 of your vaccine with mRNA designed for the original COVID variant

2. modify your vaccine to be effective against the delta variant?

As expected, here is a joint statement from Pfizer and Moderna stating exactly that. [1]

[1] https://www.pfizer.com/news/press-release/press-release-deta...


Boosters are given to improve immune response so the idea is that you improve the immune response so vaccinated people generate more antibodies against an active infection and you get less breakthrough cases.


It’s easy to find the answer to your question. One does not have to deliberately wallow in ignorance.


I was told this is a pandemic of the unvaccinated.


Unfortunately, every time Sars-CoV-2 spreads and increases its infection tally, mutation can occur which has a chance to beneficially influence selection in the next infection cycle.

Unlike how bacterial infections could gain or incrementally increase some of its antibiotic immunity or other attributes thanks to the conditions in a single host, for example incomplete or unnecessary antibiotic regimens, viral infections need to be infecting new cells in order to experience meaningful mutations. This is where immune function influences viral mutation.

Less immunity will result in more cell infection which directly creates opportunities for mutations as the virus replicates. If a vaccine improves host immunity enough that they replicate less virus, they will cause much less mutation. The relationship is non-linear because of the multiplicative nature of viral spread (r0?)

My opinion is that isn't anybody's "fault" that a pandemic virus is causing such unbelievable mayhem, but vaccinations and immunology is the truest course to achieving excellent results going forward.

Edit: Virus does not require fresh host to mutate


this isnt the case. The virus spreads within your body and the mutations will spread within the body as well. A virus can mutate and improve within the host.

What doesnt necessarily get selected for within the host is improved survival rates outside the body, ability to penetrate the body in the first place, etc. But bacteria are under the same evolutionary pressures.


>The virus spreads within your body and the mutations will spread within the body as well. A virus can mutate and improve within the host.

Agreed.

There is a bucket of vulnerable ACE-2 receptors in everybody. Once a viral infection occurs in a single person, it undergoes an infection curve within the host bucket, analogous to the infection curve of the general population. The non-linear host cell infection curve can be greatly influenced by early intervention (immunity). It can be expected that some people have a big curve that results in a more complete viral infection than in others, but the number is limited until it can move to a new person, and run a new infection curve. So the mutation can occur in that once person, but it has to replicate in a new host to see the new infection curve of the viral prototype. If one never transmits the prototype, it is moot.

Bacterial resistances like MRSA are most likely when an infection that is able to survive treatment is able to re-establish. With most susceptible bacterial cells having now been eliminated in this case, the new infection is more formidable. There are of course other mutation vectors.


> viral infections need to be infecting new hosts in order to experience meaningful mutations.

Interesting! What causes this, is there some keyword i can search for in order to learn more?


The assertion is not correct, viruses do not need to spread to new hosts to experience meaningful mutation.


Yes, it is much more precise to state that they must be replicating in order to mutate. I've edited my comment to reflect this, Thanks :)

If RNA is damaged and changed and the virus particle is destroyed or for some reason never replicates, I don't count that as mutating, but then again what do I know.


bacteria mostly need to be replicating to spread mutations as well.

There are mechanisms for bacteria to uptake dna in the environment and incorporate it (e.g. antibiotic resistance). But without replication of the bacteria the resistance wont spread.

One interesting point is that in general biology they teach that lamarckian evolution doesnt exist, but bacterial uptake of DNA demonstrates that it does exist.


Yes but the bacterial infection can go up and down or last a while, this is a general case for bacteria.

The Sars-CoV-2 virus (provisionally) doesn't seem to infect and then suppress only to re-emerge later in a new infection, or hang around as an active infection for months. People get sick and their illness lasts a big armful of days.


You were told correctly?

Brad Little of Idaho says greater than 98% of cases, hospitalizations and deaths are unvaccinated (link below).

Cases are probably the most unstable of those stats, but the point is unvaccinated folks are bearing the majority of the pain.

https://twitter.com/GovernorLittle/status/142593002008663654...


If you look at the press release[1]:

> 98.9-percent of new COVID-19 cases since Jan. 1, 2021, were people not vaccinated

> 98.6-percent of COVID-19 hospitalizations since Jan. 1, 2021, were people not vaccinated

> 98.7-percent of COVID-19 deaths since Jan. 1, 2021, were people not vaccinated

These kinds of numbers games naturally lead one to suspect an agenda.

On January 12, 2021, a grand total of 0.24 percent of the Idaho population was fully vaccinated.

> Since May 15, there have been 10-times as many COVID-19 cases among unvaccinated people compared to vaccinated people

> Since May 15, there have been 13-times as many COVID-19 hospitalizations among unvaccinated people compared to vaccinated people

> Since May 15, there have been 8-times as many COVID-19 deaths among unvaccinated people compared to vaccinated people.

As of May 15, 31% of Idhoans were fully vaccinated[2].

> Over 197 million Americans have received the vaccine safely.

According to the CDC[3],

C> As of August 30, 2021, more than 173 million people in the United States had been fully vaccinated against COVID-19.

Why does the governor feel the need to overstate the number of fully vaccinated people by almost 14% in a press release dated Thursday August 12, 2021?

[1]: https://gov.idaho.gov/pressrelease/idahoans-urged-to-receive...

[2]: https://github.com/owid/covid-19-data/blob/f6217a7ccbd2fbcfd...

[3]: https://www.cdc.gov/vaccines/covid-19/health-departments/bre...


If somebody has only had 1 shot, it is fair to say that they "have received the vaccine safely", but they are not yet "fully vaccinated". Hence the discrepancy between the 197m and 173m.


If that's the interpretation you want to go with, then the rule has to be followed consistently by reporting deaths from Covid19 among all people who "received the vaccine safely" instead of restricting such reporting to the "fully vaccinated".

Just a few lines above, he is counting as "unvaccinated" all people who are not "fully vaccinated".

Again, trust in people doing this song & dance would be higher if they did not constantly resort to tricks like this.


I see it as addressing two different concerns.

Addressing somebody whose concern is "the vaccine might not be safe", it makes sense to point to the large number of people who have been given a dose and been fine. I don't think a lot of people are in the halfway point where they think 1 shot is safe but 2 shots are unsafe.

Addressing somebody whose concern is "the vaccine might not be effective", it makes sense to look at the effectiveness of the recommended 2-shot course.

Anybody promoting anything will point to their most favorable numbers and try to keep it simple. Press release + nuance is a rare combination. This is not a research paper, it's a conclusion derived from research, and the governor is trying to get that bottom line conclusion out to the public: that it is safer to get vaccinated than not. As somebody who is smart enough to have questions about the details, you're also able to look up the answers to those questions. Does what you've found lead you to a different conclusion?


> I don't think a lot of people are in the halfway point where they think 1 shot is safe but 2 shots are unsafe.

In fact, there seems to be grounds to believe that people are extra susceptible to infection and illness during the period between the first shot and the two weeks following the second. Lumping people in that group are together with others who have never received a shot has the effect of keeping the number of hospitalizations and deaths from Covid19 among the vaccinated low.

As of 8/30, the rate of known deaths from Covid19 among those fully vaccinated has risen to 11/100,000 roughly 0.01 percent. It takes time to get exposed, infected, hospitalized, and die. We are a long way from that rate stabilizing. In the meantime, if things go as planned, there won't be anyone to compare with (but, of course, the definition of "fully vaccinated" will keep changing as needed).

> it is safer to get vaccinated than not.

Is it? Even if one has had Covid19?


> In fact, there seems to be grounds to believe that people are extra susceptible to infection and illness during the period between the first shot and the two weeks following the second.

Can you link some data on that? That would certainly change things if you are at higher risk of illness than an unvaccinated person between getting the shot and immunity kicking in. The data I had seen like from the Pfizer trial[0] indicated that your immunity keeps pace with an unvaccinated person until about 2 weeks from the first shot, then surpasses that.

> Is it? Even if one has had Covid19?

For somebody who has had a confirmed positive case of COVID I don't think there's enough data to say confidently. As far as I know natural immunity is at least as good as vaccine immunity. The risk associated with getting vaccinated seems to be low enough that it's pretty harmless though. And anecdotally there are a lot of people who are "pretty sure that cold they had last year was COVID" but never got tested. I wouldn't want those people to conclude they shouldn't get vaccinated just because they think they might have natural immunity. Again, I don't assume malice just because a politician tries to keep their message simple.

[0]https://www.nejm.org/doi/full/10.1056/NEJMoa2034577


OK, I'll bite.

Ontario had 554 new reported cases of COVID yesterday. Of these cases:

- 319 were not vaccinated (213 of these were 12+ and therefore eligible to be vaccinated)

- 56 were partially vaccinated

- 136 were fully vaccinated

- 44 unknown

In other words, roughly 16% of the population (eligible but not vaccinated) is driving close to 40% of reported cases.

OK, but reported cases are blah blah, who cares, right? Individual cases will vary in severity and everyone can make their own decisions about risk tolerance, etc etc. But the strain on our health care system is the biggest cost we all share in the pandemic regardless of personal choices, so let's look at ICU numbers instead:

- 113 unvaccinated

- 7 partially vaccinated

- 8 fully vaccinated

You can draw your own conclusions.

Source: https://www.reddit.com/r/ontario/comments/pkbgrz/ontario_sep...


> Ontario had 554 new reported cases of COVID yesterday.

> - 319 were not vaccinated (213 of these were 12+ and therefore eligible to be vaccinated)

> 16% of the population (eligible but not vaccinated) is driving close to 50% of reported cases.

Your overall point would remain valid even without exaggerating by 28%.


You mean the 50%? You're right, my math was lazy. Edited to 40%.


Where I live teachers/in-classroom workers who are unvaccinated are tested 4x per month and vaccinated are tested 1x. You can draw your own conclusions.


That unvaccinated people are higher risk of getting and spreading Covid? I agree, although I'm not sure what is the significance of the 4:1 ratio. Ontario's numbers suggest a risk ratio closer to 7:1 or 8:1 right now.


Ok clearly you don't want to discuss this honestly if you want to hand-wave away the fact that unvaccinated people have much stricter testing requirements and as a consequence are tested substantially more often.


No you are right, reported cases alone can't tell the full picture. Mandatory testing can skew the numbers and probably undercounts vaccinated people. Same if vaccinated people are significantly more likely to be asymptomatic and therefore have no reason to voluntarily go get tested (but if that is the case, it brings us back to "pandemic of the unvaccinated" to some extent).

The breakdown is similar on weekends, holidays, etc which suggests that mandatory testing does not skew the numbers significantly in Ontario at least.

But as I said: reported cases blah blah, they paint a fairly clear picture to me but there is a lot of complexity there.

What about ICU numbers?


If you're interested in my opinion on efficacy wrt severe outcomes please see my comment here: https://news.ycombinator.com/item?id=28460959


Reflexive and thoughtless media critiques really aren't very useful. "The media" is not a singular entity, this sort of critique suggests a false hypocrisy:

- Multiple entities are amalgamated into one single entity. (ie, "the media.")

- Two conflicting statements are put side by side and meant to suggest a hypocrisy. In reality, it's not a hypocrisy when two unrelated entities make statements which are at odds.

- Often, a straw-man version of the argument is used to help foster the hypocrisy claim. In this case, "this is a pandemic of the unvaccinated." This is not a good faith argument because vaccinated individuals are much less likely to spread the virus, and to become seriously ill. It is an equivocation of meaning: "can the vaccinated be involved whatsoever" vs. "is this primarily affecting the unvaccinated?"


Why is there always some smug comment about vaccine effectiveness? Comments about COVID in general have left me disappointed with this community.


What that means is that the unvaccinated are much more likely to become seriously ill if infected:

https://www.axios.com/unvaccinated-hospitalized-covid-60dc90...

It does not mean that the vaccinated cannot spread disease, however.


There is presently to my understanding a lot of claims of severity reduction, but I would like to see evidence and an explanation for it. My working model is that a consistent alternative explanation is the vaccine reduces infection risk dramatically but once infected severity can be the same.


That isn't how the immune system works. It's not a binary gate that's either open or closed. It's more like a war between two armies, and it depends on which side musters the larger army and how creatively the armies fight. If the vaccine reduces chance of infection, it will also reduce severity, because both operate via the same mechanism: antibodies killing the virus.


I've been trying to find accurate signals of this and haven't found much. I've only really spent time looking into the <50 yo cohort. I think the confounders for older folks are too significant to glean much truth from the type of data we have.

Data:

Graph from the CDC: https://i.imgur.com/Ql25IjB.png Source: https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e1.htm

Spreadsheet based on weekly UK data: https://i.imgur.com/yySYFyd.png Source (PDF warning): https://assets.publishing.service.gov.uk/government/uploads/...

And a Twitter thread on Israel for good measure: https://twitter.com/gummibear737/status/1434237628258344961

All of this data says the same thing to me. Basically if you're younger there is no significant evidence these vaccines reduce your risk.

In the CDC case: They show 1-2 unvaccinated hospitalized cases out of 100k and <1 for vaccinated (<50 cohort). It's important to remember in all of this data the unvaccinated do not represent a strict control group which is analogous to one found in an RCT.

In the UK case: ~0.5% less incidence of hospitalization for <50 cohort and effectively none wrt mortality.

In the Israeli thread: Author comes to the opposite conclusion and decides to call risk reduction 90% even though they're comparing 2 extremely tiny numbers. Both less than 1 severe case out of 100,000.

If the improvement over severe outcomes is so stark, as many claim, then where should I look to see this data such that I can come to agreement?


I have seen this "alternative explanation" or variation on it used as an equivocation to justify the choice to go without being vaccinated.

I recently saw a social media post of a person in an ICU with Covid expressing regret about not getting vaccinated, and urging others to get vaccinated. One of their "friends" commented in response to the post with parent's "alternative explanation."

Would someone please share a link to source data showing that infection severity between vaccinated and unvaccinated is not similar?


The alternative explanation does not change P(severe infection|vaccinated), so doesn't change the nature of the choice to get vaccinated. But it would imply, if proven, that the claim that vaccines reduce severity is false.

If the alternative explanation is proven, it implies that people who are vaccinated and develop an infection should react to that news the same as an unvaccinated person. In other words, even if the alternative explanation doesn't influence the choice to get vaccinated, if it is true and we are saying it's false it would mean vaccinated people are more likely to die once infected because they've been led to believe it is not as serious a concern to be infected and will be less likely to, for example, notify their doctor as promptly or go to the ER given they have been informed their risk of severe infection is low.


Lower hospitalization rates amongst the vaccinated seem to suggest less people are getting seriously ill.


No it suggests P(severe|vaccinated) is much lower than P(severe|unvaccinated) which isn't the same thing as saying the vaccines reduce P(severe|infected). It's funny I've been downvoted tho because it shows how tribalist people are about vaccines that they can't even understand an argument that has no influence on ex-ante vaccine risk assessment.


Which is an important point. While the vaccinated are still getting COVID, and even sometimes ending up in the ICU, they very often aren't ending up hospitalized or in the ICU. The vast majority of ICU patients are unvaccinated [1].

[1] https://www.ncdhhs.gov/news/press-releases/2021/08/27/adult-...


> https://www.ncdhhs.gov/news/press-releases/2021/08/27/adult-...

It's frankly irresponsible to say this. We are talking about what's essentially an exploratory study that needs a LOT of followup before taking action and pushing it in a way that's going to cause people to run scared.


It's tempting to look at vaccinated/unvaccinated as a perfect RCT and the unvaccinated are a control group. This clearly isn't the case. There are surely many confounders at play.

Looking at this release's underlying report they mention:

"The age-adjusted mortality rate among unvaccinated individuals was 5.00 cases per 100,000 unvaccinated population and the age-adjusted mortality rate among vaccinated individuals was 0.33 per 100,000 vaccinated individuals for the four-week period ending August 28, 2021."

So the difference in mortality rate is roughly ~5 in 100,000 of the population. This is a very low number. Does it obviously override any possible confounders to indicate a strong signal? Also remember this is age-adjusted. I would imagine this difference is substantially smaller for cohorts omitting the elderly. Is there a material benefit to younger reasonably healthy people? It seems the question is muddier than is typically made out.


Generally when judging how some intervention does compared to not intervening, I believe you would divide the rates not subtract the rates.


I guess you're unable to respond to the substance of what I'm saying. Nominal risk reduction of already insanely low risk is not compelling especially when confounders are present and cannot be accounted for.


The evidence definitely points the other way, see [0]. The vaccines dramatically reduce the rate of severe infection and hospitalization. The vaccines do not prevent infection, they prime your immune system to fight the infection. That is why the endpoint for the clinical trials is not infection, which would have to be determined by testing, but rather symptomatic infection.

[0] https://www.covid-datascience.com/post/israeli-data-how-can-...


There’s also population skew since the vaccination rate is much higher among older Americans, and older people are more at risk of severe illness in general.


By whom? It's a pandemic, it affects everyone. It's right there in the name.

I'm fully vaccinated, and I spent half an hour at a bank yesterday (wearing an N95) and I'm voluntarily quarantining for two weeks.

It's a deadly disease. It doesn't care about your PR slogans or your political alignment. It does care about transmission, which is why avoiding unnecessary trips, wearing real ventilators (not cloth masks, Fauci is lying to you when he says they work, all scientific evidence is that they don't), and getting vaccinated all reduce the likelihood that either you will get it or you will transmit it to someone else. Nothing gets the likelihood to 0%.


It is not the wearer that cloth masks offer protection to but to their environment. That's mostly achieved by slowing and diffusing the exhaled air and making it less likely that the infectious droplets reach others in the first place. I wouldn't want to have to wear one now that it's almost exclusively the Delta variant making the rounds but they were an acceptable measure against the wild variety/Alpha.

Look for a study from Jena, a town in Germany, that issued a mask mandate weeks before other regions if you are curious.


Whether cloth masks “work” depends on your definition of work. They appear to be better than no mask at all, but not as good as surgical masks or N95 masks.


I have a professional cloth kn95 mask. It is MORE effective then the cheaper models, according to the technical u. In Berlin. The number of layers, 5 in this case, and anti viral agents contribute.


It's extremely unlikely you're going to get COVID from your bank trip. Many, many healthcare workers treated COVID patients every day for nine months unvaccinated and didn't get COVID. You are vaccinated, it's only half an hour, and it's unlikely that anyone in the bank has COVID.

IMO wearing better masks is a great thing, and so is minimizing indoor time with strangers, but it's also possible to overdo COVID protection.

Most of the spread of COVID is among unvaccinated people doing things indoors and unmasked. Unfortunately, you being even more careful will not affect their behavior.




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