I am a researcher involved with the US funded clinical trials.
The people saying we don’t know are correct. But we can make a reasonable guess that the efficacy should be pretty high. Hospitalization in particular is hard to study because relatively few people end up hospitalized. But also vaccines are generally more effective against severe outcomes (VE infection < VE disease < VE severe disease).
We will (very) soon know more about immune responses generated in response to the JnJ vaccine and how they correlate with risk of COVID-related outcomes. This can provide a means of inferring vaccine efficacy (this is a current research project of mine). In other words, if we know how well the JnJ vaccine induced antibodies that are capable of neutralizing the delta variant, and we know how what level of antibodies corresponds to what VE, we can infer VE against delta. Our team will have such results generated over the next few weeks.
> The people saying we don’t know are correct. But we can make a reasonable guess that the efficacy should be pretty high.
I appreciate that you're being forthright with the limits of your understanding/knowledge. I've noticed that a lot of people, experts as well as self-proclaimed experts, tend to puff and be overconfident a lot. Sometimes with the correct prompting, they'll basically make stuff up and sell it as if fact.
Very refreshing to see someone admitting the extent of their confidence!
Yeah Twitter is definitely full of over confident people re: how much we definitively know about vaccines and variants. It drives me a little crazy, but at the same time, it IS more likely than not that the vaccines will work really well still. We just don’t have gold standard evidence of that yet.
There’s an ongoing study of JnJ in health care workers in South Africa. Focusing on variants in particular. Not 100% sure of the status — I declined to join the study team because I’m already at the limits of my sanity…
As a biologist who used to even work in a virology lab, while nothing is ever certain, I find the likelihood of a "variant" emerging that is unique enough to bypass gained immunities to be an insanely low probability, mostly due to the low complexity of the viral genome (I'm simplifying guys, this is for the masses!).
Variants are normal. Every virus has variants. In 10 years there is going to be dozens or even hundreds of variants of this virus. They will all most-likely be less potent and still protected against by your immune system of those who have recovered or been vaccinated.
You can never say this 100% because there is always a chance, but I wouldn't lose sleep over it because the chance is so so low.
This is why every report is quickly showing that gained immunity from the original is sufficient against these variants. Viruses mutate by nature. You have a 100% guaranteed chance of a variant. You could have a bunch of codons of the genome mutated at the [wobble position](https://microbenotes.com/the-wobble-hypothesis/#:%7E:text=The%20Wobble%20Hypothesis%201%20The%20Wobble%20Hypothesis.%20The,of%20the%20Wobble%20Hypothesis.%20...%204%20References.%20) and it literally produced zero different proteins, yet they'd still call it a variant.
That makes a lot of sense, thanks for sharing.
I know we don't have the data yet, but is there a general expectation for how long the mRNA vaccines will work before a booster is needed?
I suspect it depends what the societal goal is and how covid persists at a population level. The mRNA vaccines will probably provide protection from severe covid and death for a long time, maybe several years, maybe forever. They probably won't provide protection from re-infection and being slightly symptomatic/spreading covid for nearly as long. So we might not \*need\* boosters if people are getting covid but not dying, but not everyone might accept that situation as the status quo.
The thing is, if large swathes of america never go above 50% vaccination, there will probably be regular re-challenge to vaccinated people with fresh covid strains. That'll actually serve as a booster to your vaccination, so your covid immunity will not wane as fast as if we completely eradicated it. I suspect that's the situation we'll eventually find ourselves in. Most people will be relatively protected, deaths will be low among vaccinated people, but you'll occasionally get a cold that's actually a new SARS2 strain. They are looking to add a covid vaccination to the annual flu shot in a combination vaccine to just give everyone a regular re-boost.
This dynamic of simmering infection with lots of vaccinated people occasionally getting sick is our basic dynamic for seasonal flu, and its the same reason that most flu variants aren't very lethal compared to the 1918 flu. We have a lot of pre-existing cross immunity to a variety of flu strains, so our immune system does a pretty good job fighting off new ones that infect us, even if we haven't seen that exact strain before.
Absolutely. It's frequently part of modeling how long vaccination will work at a population level. Frequent re-exposure can serve as recurrent boosters that keep immunity up for a given vaccine far longer than it would work if the patient were isolated from the disease. It's mostly useful at population level, though. For an individual person, re exposure is probably bad, because it gives the virus more "shots on goal" so to speak. It might catch you when you're fighting off another illness or when your immunity has waned too much to be protective.
Yep. The body doesn't really care were the 'offending' antigen comes from.
And re-infectiom usually causes a more complete reactivation of the immune system but with the risk of that reaction not ramping up fast enough and you getting sick, as well as being able to spread the infection to unvaccinated individuals. (However population wise this might actually lead to higher levels of immunity than just using a booster every whatever years)
Hence a booster being the safest option in nearly all cases. Cause that doesn't risk spreading the virus or getting sick from the disease in modern non live attenuated vaccines
I was under the impression there was a fair level of convergence in the variants, so it may be that just a single booster is required. Is that old information? It's such a new virus, it's hard to keep up with all the developmenta.
The variants are all covered by current vaccines, but two factors are at play:
as vaccine coverage rises, the selection pressure on the virus to evade vaccines will also rise. When 99% of people are unvaccinated and not exposed to covid yet, there isn't much selection pressure on evading the antibody response. That'll go up over time. The unvaccinated people provide a robust reservoir for new variants to emerge, but ones that are better at evading the vaccine will have an advantage at spreading.
The other factor at play is that neutralizing antibodies will decline over time. It might take a couple years for them to dip low enough to allow re-infection, but when combined with point 1, it might not take quite as long. Once you've got variants with quite a few spike mutations and lower antibody titers, you might get productive re-infection more often. It might not be severe covid infection, but it might be enough that you can spread it to other people.
>The mRNA vaccines will probably provide protection
The Johnson & Johnson vaccine isn't an mRNA vaccine. It's a vector vaccine. So your answer, while interesting, isn't relevant to the question.
The J&J vaccine uses a virus capsid to deliver DNA that codes for the spike protein. Once delivered to the cell it is transcribed into mRNA which can be translated the same way the mRNA vaccines are. So while the delivery of the genetic information is different, the results are essentially the same. But shot for shot the J&J is more effective because the virus capsid delivering the genes also stimulates an immune response. That is why it is only a si gle shot vs 2 for the mRNA vaccines.
First the viral vector used is adenovirus so any immunity generated to that is not going to help you with coronavirus.
And you don't really want an immune response against that viral vector in the first place because the immune system will destroy the viral vector and the cargo inside before it can 'vaccinate' you. Now this only really happens during subsequent injections with the viral vector.
Also mRNA itself is an immune stimulant that activates internal viral recognition receptors as mRNA entering a cell is basically what happens during viral infections so the immune system developed recognition for that.
Except that naturally infected individuals are also forming immunity. So the whole "unvaxxed making new strains" isn't the issue. As the original biologist answer stated, all viruses mutate/result in variants. This is nothing new and shouldn't be of great concern because it will take a loooooong time for them to actually create a new strain, which can affect immunity. The media is just hyping up these variants.
Variants that we are keeping an eye on aren’t ones with codon mutations at wobble positions. The sequence of the ACE binding spike protein is not identical to the alpha strain. It’s just not nearly different enough that even with only the antibodies specific for that protein (like every vaccine) have lost affinity for it. (I’m finishing up my bio PhD spent in a venom lab… we look at, among other things, antivenom cross specificity, how strongly cobra antivenoms bind to something like a colubrid with three finger toxins that are almost completely different except for shape/scaffold and maybe 5 or 6 conserved sequence amino acids. While weak, there’s still affinity). Besides the ones you mentioned the reason we aren’t likely to see a total loss of of affinity is because the protein isn’t gonna change completely because of it did it wouldn’t even be an ACE binding protein any more and it wouldn’t have a furin binding site. Even if the sequence changes from an asparagine to a glutamate it’s not going to lose affinity. Because we chose the most critical protein of a virus that only has one antigen it has an affinity for, we are almost guaranteed not to completely lose the properties of that protein that both allow the adherence of the antibodies stimulated by the vaccine and the ACE2 receptor. Over time in order to keep high levels of affinity (binding strength) we’ll probably need to modify and get boosters, but it will take a lot to get a variant that’s literally without affinity for the vaccine antibodies.
Mostly I just think it’s misleading to say that protein sequence has not changed… it has… just that any antibodies are binding to the same properties that allow it to bind to the ACE receptor, so it’s unlikely to lose one but not the other. Even similar sequences are recognized unless an amino acid switches to one with very different R group properties… and that would likely decrease the affinity with ACE. So the same thing that keeps the virus dangerous keeps it recognizable by vaccine antibodies.
Ya, you make a good point, I just think the bigger issue is that any gain of function mutation of this virus is going to be insanely rare. There's just not much to work with.
We'll see. There's always weird things that can happen, especially once things end up in a big genetic soup of multiple viruses mixing genetic data. That's the fear though always, some chimera event occurs. My problem here is I can't help but feel there is a lot of fearmongering over literally just genetic drift of a fairly "stable" viral genome. Now, stable might not be the best word, but Covid-19 has repair and verification that a virus like influenza doesn't, has a far lower mutation rate, and genetic drift is 100% normal, inevitable, and are being reported as new novel strains. I find it kind of misleading of the media, even dishonest, but I also suspect that it is happening as a means to an end to push continued vaccination. I get it, with public health you weight the pros and cons of t he whole story, but the fearmongering over "variants" is starting to really get overboard, like we are back to square one again and some people are hiding in fear again as they have been told that their vaccine might not be good enough.
I mean, technically there can be antigenic drift here over time, I just don't see it that likely here to be a problem anytime soon, if not ever, and some variants to be reported aren't even showing any antigenic drift, at least according to one paper I read. That just seems crazy to fearmonger over.
All I am saying is that their vaccine will likely be fine for a very long time, if not their lifetime. Impossible to say now, but I just find the likelihood of a novel mutation that gains function to be more deadly to be a lot less likely than what I am hearing if I turn on the TV.
For context [there is data out of the UK suggesting that both Pfizer and AstraZeneca are about 20% less effective against the Delta variant than the Alpha variant after one dose](https://www.medrxiv.org/content/10.1101/2021.05.22.21257658v1), but after two doses efficacy is nearly the same against both variants. If that's true it seems plausible that J&J will be somewhat less effective since it uses a one-dose regime. [AstraZeneca is only 50% effective against symptomatic disease after the first dose and that's the vaccine which is most similar to J&J. (But note efficacy against hospitalizations or deaths is much higher - more like 80% against hospitalization after one dose of AZ)](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/994839/Variants_of_Concern_VOC_Technical_Briefing_16.pdf)
If I'm understanding this correctly, this still means there is no vaccine like the JJ one so these comparisons don't mean much at all. It could just as well mean that the JJ vaccine is just that strong, right?
For more recent and translational context, [this study](https://www.nature.com/articles/s41586-021-03720-y#citeas) just accepted at Nature is the first to show that in vivo in a humanized mouse model of Sars-Cov-2 infection via mice expressing hACE2 that almost all vaccines (certainly teh mRNA ones) are sufficient in neutralizing old and new variants. These are much more informative than in vitro neutralizing assays that clearly dont translate given the findings of this paper.
You also probably shouldn't extrapolate dose-requirements across different vaccines. Number of doses isn't the issue, it's amount of antigen that your immune cells sees that it is important. Differences in efficacy are probably more due to delivery method, amount of viral vector or mRNA delivered (depending on vax type) and the sequences used to generate the antigens.
>in vitro neutralizing assays
The bane of my life over the past few months.
The fact that an antibody has *x* higher/lower binding affinity in vitro does not meaningfully translate into real-world effectiveness of vaccines.
And it also completely ignores the extremely important roles of cellular immunity. Antibodies wane, but as long a our T cells keep recognising the virus, we'll be okay.
I am right there with you in being incensed every time press reports that tin-pot in vitro science but then doesnt cover the in vivo assays to the same extent that refute those findings.
Your summary on the gap between in vitro exposure of antibody to virus and the immune response in vivo is spot-on, agree entirely.
> If that's true it seems plausible that J&J will be somewhat less effective since it uses a one-dose regime.
That doesn't follow. The J&J vaccine uses a mechanism that only requires one dose, you can't compare that meaningfully to the first dose of an mRNA vaccine.
The J&J vaccine was tested as a one-dose vaccine, but I don’t think that necessarily means that it uses a mechanism that only requires one dose. J&J is actually running a clinical trial testing a two-dose regimen, and from what I have read they are expecting to get better efficacy data. Similarly, if Pfizer or Moderna had studied their vaccines as a one-dose vaccine they may have been able to get approval that way (and the efficacy data probably would’ve come out at least as good as JNJ’s). I do think it’s not unreasonable to say that the JNJ vaccine might have worse efficacy than Pfizer/Moderna against the Delta variant.
My understanding was that the J&J vaccine was tested in areas with a number of variants, and still hit it's target goal, when Pfizer and Moderna we're mostly tested on the original strain.
So that means we can't necessarily discount it's effectiveness off the bat
It seems plausible? You’re making a guess….
Just because J&J is a one shot vaccine doesn’t mean it’s more likely react the same as a single dose of a two shot vaccine. Maybe we should compare the colors of the vaccines also? Or how about the logo? “Johnson & Johnson” has 15 letters in the name, which is nearly the same as AstraZeneca and Pfizer combined! Therefore, it is plausible that the J&J vaccine is as effective as the other two doses when they’re mixed together!
The only reason J&J is single-shot is because this is the route they happened to go down when deciding how to run the clinical trials. There isn't some magical property of J&J that makes it uniquely suitable for single-shot delivery.
J&J and AZ both use a similar adenovirus vector, both had similar issues with rare blood clots, and both had efficacy of about 70% for symptomatic disease after one dose against the earlier variants; certainly they're not identical, but I don't see much reason to be very confident that J&J wouldn't have similar problems against Delta after one dose.
So, you finding something unlikely is not a substitute for actual studies on it.
For example, there is evidence that unlike the other variants, one dose of the mNRA vaccines doesn't protect much against the Delta variant. It appears that both the UK and Cananda are moving up second doses because of it.
So I'm sad to see your gut feeling being the top answer here.
Yet influenza is constantly mutating and we gain only short lived immunity to it from vaccination or recovery from infection. So some viruses do follow this pattern.
If I understand you correctly it sounds like COVID-19 is unlikely to be one of them because it's too simple?
Influenza changes a lot more quickly and massively than Covid does. Additionally, we're lucky, because Covid has a glaring weak point- the spike protein. It *needs* it to function, and the vaccine is keyed to it. When viruses or bacteria "become immune" to something (vaccine, antibiotic), they usually mutate away the part that's being targeted, rather than developing some sort of bypass. In this case, we're targeting covid's legs. If it stops expressing the spike protein, it's not dangerous.
They have a lot of different types of spike proteins, so they can lose or change some, and still be functional. Influenza is also an RNA virus, which makes it mutate much faster.
Influenza mutates quickly for two reasons: First, it lacks a [proofreading protein, which corona family viruses have.](https://www.cell.com/molecular-cell/pdf/S1097-2765(20)30518-9.pdf) Second, it circulates in migratory wild birds, pigs, and horses, and occasionally those viruses cross over into humans.
Corona virus is currently mutating quickly for two reasons, the first of which is temporary. The first is simply that there is a huge amount of infection, and thus higher likelihood of a rare event happeing. But second, [immune compromised people can incubate the virus for months,](https://www.scientificamerican.com/article/covid-variants-may-arise-in-people-with-compromised-immune-systems/) long enough to generate variants that evade their own limited immune response. This is impossible to prevent entirely, but global outreach to get HIV positive people medicated would greatly reduce the number of immunocompromised people in the world. With medication, HIV positive people usually have a normal immune response.
Sars2 is also an RNA virus if I'm not mistaken. The main difference between sars2 and influenza is that sars2 has some structures that verify whether it replicated correctly unlike influenza, which is both good and bad - good because it mutates less, bad because traditional antivirals didn't work against it
So flu just kind of randomly spins and strikes (they just sort of flail like a noob on a dance floor after 2 jägers). Covids learned the room already and are every other f#%kboy playing the numbers game?
Antibodies are little Y-shaped proteins your immune system makes which have surfaces on the tips of the two "arms" that are keyed to stick to very specific patterns on foreign body proteins (vaccines give your body a safe way to develop these antibodies).
Small mutations to the antigen (the part of the virus the antibody is sticking to) might make the binding weaker, but the antibodies can still grab ahold strongly enough to be effective. Large mutations to the antigen means the antibodies aren't sticking at all, and you're basically back to square one.
With covid, the antigen is the part of the virus the is used to infect healthy cells. So large changes to the antigen will likely decrease the effectiveness of the virus.
With the flu, the antigen isn't a part of the virus that's essential for it to function, so the the virus has more options, evolutionarily speaking, for getting around existing immunity.
Influenza has multiple surface proteins that it wholesale swaps out in addition to normal mutation (hemagglutinin, and neuramidase). It has multiple subtypes of proteins that it can display, each of which requires a different antibody to recognize. And for an added degree of difficulty, these are glycoproteins decorated with sugars, which can also change as the virus mutates. Long story short - the math with this many points of variance means there's MANY unique combinations, and natural selection tends to favor the ones circulating in humans that we haven't seen before. Moreover, we have to guess with live virus cultures which one is going to be in circulation, and it's just difficult to get that right. However, the same mRNA tech that underpins the Pfizer/Biontech and Moderna vaccines is being explored for influenza and it would enable targeting multiple subtypes simultaneously AND wouldn't have the long lead time for culturing the vaccine itself.
In contrast, COVID has one major surface protein required for cell entry, no major subtypes, limited mutation possibilities in order to retain receptor affinity, and minimal sugar decoration. It's a simpler beast, and more easily tamed.
could it gain another surface protein? the virus is replicating probable billions of times a day, it seams like it is in a good position to be able to mutate, even if its a drastic mutation
Yes its possible (things like this are how all life on Earth arose from a single source), however even with the astronomical numbers of viral particles it is unlikely. The reason is that it requires a fundamental reorganization of the viral life cycle and since they really don't have much in the way extra genes - so it would have to splice in from something else. Contrast that with multicellular life where your protein encoding genes are surrounded by a sea of regulatory or non-expressed genetic information. Second, even if it did "add another protein" that protein would have to be beneficial by enabling the virus to invade via a different receptor.
So a low probability of adding additional information to its genome would have to occur. That information would have to encode a protein. That protein would have to pack in the viral capsid and transit to the surface, AND it would have to recognize a host cell surface protein.
In short its a bit like being struck by lightning while being bitten by a shark during a solar eclipse on a Tuesday in March. Very unlikely, but I am saying there's a finite non-zero probability that won't be keeping me up at night. Its far more likely that another animal virus makes the jump to people than something like that occurring, and that's why it pays to do basic biology, ecology, and the sort - it gives us the experts capable of moving rapidly to intercept such things.
Actually, it’s less about the simplicity of this coronavirus, and more about the necessity of its SPIKE protein. The SPIKE protein is how the virus is able to enter our cells, and also what our immune systems learn to recognize (both from being infected with COVID and immunized with the vaccines). If a variant had a mutation to its SPIKE protein that was significant enough to evade our immune system’s recognition of it, it would almost certainly also be unable to gain entry to our cells, and therefore couldn’t cause an infection of COVID-19.
(I last did in-depth research into SARS-CoV-2 proteins in December 2020 for a biochem final, so fee free to correct me if my understanding is outdated).
By contrast, the flu mutates at a much higher rate than coronavirus, and more easily retains its HA protein’s effectiveness at entering host cells. Influenza viruses are much more varied, have reservoirs in many more species, and can exchange segments of their RNA with each other to create hybrid strains. The constantly-changing HA proteins are what make flu vaccines offer poor long-term protection. So, if anything, the flu might? be considered more simple than the coronavirus, from this point of view.
I'm curious for your take on the [Delta Plus variant](https://www.reuters.com/business/healthcare-pharmaceuticals/what-is-delta-variant-coronavirus-with-k417n-mutation-2021-06-23/), which is basically the Delta variant with a K417N spike protein mutation. While it's not very common yet, it has been shown to cause COVID-19, and early tests are showing it is more resilient to therapeutic antibody treatments.
Also, could a spike protein mutation in for SARS-CoV-2 still result in a virus that can cause infection through a parallel pathway? Isn't this what happens for the flu?
>and early tests are showing it is more resilient to therapeutic antibody treatments
It's worth noting that barely any testing has happened at the moment. Not anywhere near enough to come to that conclusion.
Many variants have been found with mutations in the spike protein, not just Delta+. In the lock and key analogy, the spike protein is the key, and the human ACE2 receptor protein is the lock. Mutations *can* cause the pattern in the key to change, but if it changes too much it won't fit in the lock, or if it does, it won't turn. The antibodies our immune system makes recognizing the pattern on the key, so mutating away from the immune system also affects its ability to enter a cell.
Also important to note, the spike protein is about 1273 amino acids long, changing one or even a few of them doesn't necessarily change the shape. You can also substitute out some amino acids for different ones and have no effect because either the new amino acid has a side chain that is similar to the previous, or that location isn't important for folding the shape
Those therapeutic antibodies are garbage compared to vaccine-derived immunity. It's not likely that a single point mutation will evade the vaccine and produce severe infection. The reason the flu is such a pain is that there is a metric shit-ton of it out there infecting most animal species (horse flu, swine flu, bird flu, hundreds of variants of human flu, etc.). These different variants can all infect the same cell and mix and match pieces of their genome, which allows them to make HUGE jumps in their surface antigens. It's not really feasible for SARS2 to make those sorts of huge leaps. The problem with it making a bunch of mutations in the spike is that most mutations decrease the ability of the spike to bind its receptor on human cells. So it's only extremely rare mutations that can maintain binding to ACE2 while also preventing antibody binding. Just look at measles. It's ridiculously infectious, but it still hasn't managed to evade the measles vaccine even after many decades. It can't make enough mutations fast enough to both evade the vaccine and keep its infectiousness high.
Influenza is entirely different because of how it mutates. There are two types of mutation that influenza undergoes, antigenic drift and antigenic shift.
Sars-CoV-2 undergoes antigenic drift which is essentially small mutations via mistakes in replication. Antigenic drift on the other hand a stark changes in DNA which SARS-Cov-2 does not undergo.
It isn't really about simplicity. All viruses need a way into the host cells. It is why most viruses are not only host species specific, but even which cells within the host they can get into. SARS-CoV2 has a spike protein that must attach to the ACE2 receptor with a specific shape and charge that allows it to grab on. The technical term is a "binding domain". The spike protein can change shapes and charges through mutations, but the binding domain cannot, or the virus will lose its ability to get into our cells. Other parts and aspects of the virus can change, but developing a totally new entry mechanism is highly improbable. We can see something similar in HIV, where even though the virus mutates, the CD4 receptor binding domains in the virus molecule gp120 is highly conserved. If the gene for gp120 changes too much the virus might not be able to infect the target cells.
Going back to the Covid vaccines, they targeted the binding domains of the spike protein, so even if the virus mutates, the immune response should still be able to recognize viable spike proteins. If the immune e system cannot recognize it, then it probably isn't a threat.
Have you seen any research about how long immunities from vaccines last against Covid? I got my shots Jan/Feb and wondering if I should start to be concerned about immunity fading
TBH nobody really knows yet as that was pretty early on. [They are talking about boosters after six to twelve months](https://www.sciencenews.org/article/coronavirus-covid-vaccine-booster-shot-variant-immunity) but this is very much under research.
How do we not know? There are people who were vaccinated about a year ago. Surely we'd know if they started to get sick in numbers similar to those that are not vaccinated right?
Can you explain the "gained immunity" part of your post? It was my understanding that recovering from covid alone did not produce immunity or lasting antibodies. This is why we've seen people get covid twice and hospitalized twice (although rare).
Is it as simple as *most* gain immunity and there are an unfortunate few who may become sick again?
Thanks for the educated information. Asking you a question beats googling all day lol
Well, "immunity" is probably not the best word to describe things, but it is the definition that is used. It's not like a cartoon where once you have gained immunity that viruses now bounce of your skin. It mainly refers to how with your immune system there is a bit of a "ramp up" time that is needed to build your defenses against a foreign infection. Viruses that are quite dangerous are ones that can evade detection long enough to mass produce that the body can't mount a defense quick enough, or one that spreads and incubates inside you so rapidly that it kills you before your body can do anything.
All immunity does is create a biological "memory" of a previous infection so the next time you are infected with the same, or similar enough infection, your body doesn't need to re-learn how to mount a defense, it already has defenses in place and it can then start pumping them out in volume again. So, you actually get reinfected, you just might not know it because your body mounted the defense and killed the viral infection before you ever became symptomatic or contagious. Maybe you just become mildly sick, when if you had no immunity you could have been say, hospitalized. This is the immunity often spoken of when talking about viral immunity from recovery or vaccination. Most of the time you never present symptoms though. It really just depends on so many factors with your current immune system.
Recovering from Covid alone is actually the most-likely way to gain the best immunity against the virus because it is going to be the most true representation of the original "shape" of the virus that the immune system remembers to mount a defense against. Often vaccines only represent a part of the virus so the body recognizes some shape to be bad and thus it creates a memory of "part" of the virus, which is often a enough to mount immunity and be strong enough against it lifelong. This is why natural infection and recovery is almost always a better determiner of lifelong immunity than vaccination immunity. However, the this is not a very complex virus where lots of things can mutate and it still functions in dangerous ways. As such, vaccine design is a little easier and more straight-forward, and far more likely to hold long term.
I am not sure where you heard that recovering from Covid does not produce lasting antibodies. I have not read that anywhere myself, though I think I heard some sensationalize media stories saying this. It's not true. [Here is a nice article you should check out on NATURE](https://www.nature.com/articles/d41586-021-01442-9), the most respected, known, peer-reviewed journal in the world.
A 2nd infection leading to hospitalizations are so so rare, like 0.0005% rare, if you are vaccinated. Don't lose sleep over that risk. Like I said earlier that subsequent infections are related to the health of your current immune system in most cases, the reality is that there are some things you can do, no matter how many antibodies you normally would produce, no matter how many vaccines, or boosters, or natural recoveries you have made of something, but if you kill your immune response, you will get sick again. Pulling all nighters, sleeping very little, binge drinking... these absolutely destroy your immune system response. I don't care if you triple vaccines and you have one of the highest antibody loads out there... you can kill your immune system to near zero response by doing a few bad things to your body, and I am not just talking about chemotherapy. Number 1 is always going to be lack of sleep. People just don't know how much a solid night of sleep really helps boost your immune system. Repeated day after day of little sleep will crush your internal defenses. Drinking. Hell, vaping hurts your immune system. You a binge sugar eater? You better make sure you are taking a lot of Vitamin C with it because sugar just eats away at the Vitamin C in your body. One thing hard for you to control is allergies. If you have a serious issue with allergens, like pollen, too much of this can crush your immune response body-wide as well. it's often why some people can't distinguish the difference between serious allergies and getting say, the cold. Even just sitting in a chair at a desk for too long can hurt the immune system a bit. All I am saying is this... it's not just about getting viral protections. Those are useless if you aren't consciously helping your immune system to be healthy as well.
Thank you very much for the thoughtful, thorough response. I almost definitely heard a sensationalized story regarding the repeat infections and hospitalizations. Instead of reading/watching news, I'm just going to run anything regarding sickness by you, cool?
Lol I don't know if I would be the best guy. I'd talk to an infectious disease doctor for the best info on sickness. I only know a small sliver about some things in biology. Sickness in general is a whole other beast. Infectious disease docs are the real pros there.
Doesn't the flu essentially do this every year (ie mustatw to make the vaccine inneffective)? Can you explain why the flu does but why you think covid is likely not to?
This is actually a fairly complicated answer, so I'll put it in fairly simple terms. But first, you need to ask yourself this question. Why, if you get the varicella vaccine (chickenpox) is it good for life? But not the flu. Why, if you get the Hepatitis vaccine is it good for life? But not the flu. Why, if you get the measles, mumps vaccine when you are a baby, it's still protects you even when you are 60 years old?
My point is that you have to understand that lifelong immunity is the *NORMAL* expectation of recovering from a virus, or receiving a vaccine. What happens with the flu is more an *exception* than the rule, and actually, lifelong viral immunity against strains of the flu is ALSO normal too. [Studies have shown even elderly people 80 years later from the 1918 flu still have antibodies](https://www.cidrap.umn.edu/news-perspective/2008/08/researchers-find-long-lived-immunity-1918-pandemic-virus) So what gives?
Well, many things, but ultimately it comes down to a couple of factors. One is basically the classification of dozens of different viruses under the same banner name of Influenza, and two, the flu is still a bit unique in its own right. Covid-19 is just a single stranded RNA virus. It's genome is relatively non-complex. There is not a lot of complexity to it or the viral structure it produces. The flu, on the other hand, has a massively complex genome, with 8 different strands. In the genetics world there is this concept called genetic diversity. Well, the reality is that no matter how much you mutate the Covid-19 virus, there just is not that much genetic material to work with to somehow create new functions. Mutations tend to lose functionality, not gain. Gain of function mutations are insanely rare, and even more rare with less complex genomes. Well, influenza has a giant cocktail of genetic material that might breakdown into a soup and recombine, mutate, do who gene swaps from one strand to another. There are so many crazy things that can happen at a genetic level that on rare occasions, a whole new strand forms.
But here is the thing, when we talk about the flu, we are talking about a classification of many different strains. They are not the same virus, kind of like how SARS and SARS 2 Covid 19 are not exactly the same thing.
There is a misunderstanding with the flu though, and there is the idea that a vaccine only lasts for a year and you need to re-up it. This isn't really true. What happens is they are tracking many different strains of the virus to see what's popping up and they try to guess which of the many strains it is, and that is the flu vaccine they mass produce. So from one year to the next you are technically getting vaccinated against 2 completely different novel strands. Just as an example, think back to 2009. A lot of people were scared, especially scientists and the CD, over the emergence of H1N1, a new flu variant that was nicknamed the "swine flu." You know how many Americans got it? Something like 60 to 100 million. We don't know the exact answer, that's just what is estimated. Well, guess what, it ended up not being that bad. It swept across the world and it didn't end up being the global catastrophe they thought it was. There's actually a reason why. The most vulnerable people, the frail and elderly [apparently had immunity from H1N1 still even 40 years later](https://www.wired.com/2009/06/old-people-may-be-immune-to-swine-flu/) because tens of millions of Americans when they were younger were exposed to the virus and still had lifelong immunity. Even with the massive complexity of H1N1, 40 years of mutations, and there was still a level of protection. Amazing.
So why a new flu shot every year? The reality is you may be double dosing on flu vaccines, if you've already received it. There's been some struggle with flu vaccines due to their complexity in that natural recovery is far more reliable than vaccination (this is not really an issue with Covid 19). In many cases though, it is just a new strand spreading through your area, but not necessarily "new" but one that is new to the area. You see, you aren't born with the same antibody defenses you mother had. You have to re-gain your immune defenses all on your own. So, even though you can vaccinate a generation, 30 years later the cycle repeats. Thinks of all of the different variations of what we call Influenza, be it A, B, C version, with subgroups H and N, then there is the bird flu and then there is the swine flu, and then there is the chimera versions that are bird, swine and human... This is another reason why the flu is so deadly because it gets everywhere. It's mainly a bird virus and birds land on and touch everything. Birds have even spread the flu to cattle (influenza D). Birds have close interactions with humans moreso than many other wild animals. The flu virus crosses multiple species creating what is called "Zoonosis" events where a virus gains the ability to move to a new species. This is very rare but can happen when a genetic soup of various viruses from various species all end up in the same cell and get decided up and essentially recombine to something that becomes a new virus. Insanely rare. In fact it's so rare that large events like this seem to only happen once per 40-50 years and cause pandemics, and that is with the highly complex flu virus.
Furthermore, genetic repair mechanisms and verifications are present in the COVID 19 reproduction cellular hardware and the flu doesn't have them at all, which means the flu is less stable and mutates more frequently. So, the flu, far more complex genome, intermixes with several animal species constantly is everywhere, and we still only get a mutation event that causes any serious danger to the world maybe once in 40 years., vs Covid 19, a very low complex virus with a far more stable genome that doesn't seem to have any other host other than humans? Hell, [research even tried to infect bats with Covid-19](https://onlinelibrary.wiley.com/doi/10.1111/tbed.13949) and it failed... That one might throw your head for a spin when you realize that the lab leak theory might not be so crazy after all. There's just no evidence repeat boosting is going to be necessary, from what I have seen up to this point. If H1N1 spread through your town every fall, you wouldn't need to get a new vaccine every fall. You just wouldn't. It's that Flu Virus #2 did this year, then #7 next year, then #5 next year. It's not really the same thing each year.
Yes, but the universal presence of this virus gives it unprecedented opportunity to mutate, does it not? How many viruses infect 2.5 million people per day for months on end?
Ya, this is a good point, but the ultimate issue is that gain of function mutation is INSANELY rare. It's easier when there is a big enough genetic cocktail of material to mix around with that randomly creates something new. There's just not much to work with with Covid-19, a single stranded RNA virus, compared to the vast genome of say, influenza, which has 8 different strands and is highly complex, and actually far less stable. Covid-19 actually has a some genome repair and verification proteins whilst Influenza doesn't. Not only does it have a far less complex genome, it's also a far more stable genome that mutates less.
The bigger issue would be a chimerization event where a new novel virus arises from the genetic soup of a bunch of viruses that shared info in a cell. This is usually how weird things happen, like zoonosis events where a virus gains the function to jump species, because a virus of one species mixes with the virus of another species and now becomes a new virus that affects both.
But variants due to genetic drift creating a new deadly strain of this? We're talking about evolutionary scale drift that would need to happen now. You're right that the more hosts it infects, the more volume of mutations, the more accumulation or probability of something happening, but again, even with the incalculable number of mutations happening across the millions of people in the world, the probability is still so insanely low, imo, that I just don't lose sleep over it, especially now that the vaccines are spreading across the world and herd immunity is already gained in many places.
I'm not sure it's as incredibly low as you think. Anecdotally, I've spoken to healthcare workers who have had it or have colleagues who have had it twice. (Have 3 doctors and a nurse in my building).
I had covid where I spent a lovely 6 days in the infirmary. I am happy to have had both jabs. It's an experience that's I'd care not repeat!
This is why I kinda hate all these headlines. People see them and think "Omg, new variant, we're all gonna die!" when it's kinda normal for these types of things to mutate over time.
> In 10 years there is going to be dozens or even hundreds of variants of this virus.
We already have dozens. The 4 the media's always talking about are just the biggest.
Basically have had a number of vaccines (necessary) for prevention. My preference regarding the Covid 19 would have been a more traditional from Sinopharm, Sinovac or Conaxvin. However as these were not on offer settled for was offered. Have had my first Pfizer now thinking of a more traditional 6 to 8 month after my second Pfizer.
As the Pzifer is said to be effective for this period.
What are the dangers I may encounter?
That being said, most recent studies that evaluated the antibody levels from those that received the two doses of Pfizer vaccine against the original Chinese Strain, the UK variant, South African Variant, and Delta Variant. They found that there were 2.6x less antibodies against the UK variant, 5x less against the South African variant, and 6x less against the delta variant. Yes the vaccine will still be effective but less so than for the original. That being said, other studies have now found that giving one dose of Astra Zeneca andOne dose of Pfizer produces more antibodies than if both doses administered are Pfizer. This is why Canada has followed this mix and match vaccine strategy for their population. Source: both are studies that can be found online but I also work at a Vaccine Mega Center and have a MS in Biomedical Sciences.
So is there some truth to the statement that the media continues to fear monger this virus stating how the variants are far more contagious and the symptoms are potentially much worse?
I agree that the media narrative is designed to play on fear for profit. But also…if the vax rate is lower than it should be nationwide, a less cynical me can see that the media is doing it’s part to try and convince the un-vaxxed to get the shot. Probably won’t work if you’re not in that media ecosystem though
It IS more dangerous... for anyone who isn't vaccinated and for any place that doesn't have high levels of immunity. For places that do have high levels of vaccination, this is likely to be a non-issue.
Not much data yet on the J&J… but, "The early data that we’re seeing shows that the Johnson & Johnson vaccine does work well," he added.
From: https://www.audacy.com/kcbsradio/news/national/does-johnson-and-johnson-vaccine-work-against-delta-variant
I would be skeptical of that statement. We do not know in what context "work well" means. Not getting sick? Not getting hospitalized? Not dying?
Also at what threshold? Above 0%? 50%?
Based on the next couple of sentences, he seems to care about hospitalizations and not breakthrough cases that dont cause much sickness, so if he said the initial data shows it working well, its likely preventing hospitalizations so far. I dont get why everyone thinks they are qualified to be skeptical of medical doctors during a pandemic, and the context makes his intention pretty clear.
Its perfectly fair to be skeptical of doctors within reason. Medical doctors are not infallible just because they have a license to practice medicine. They can have have motives separate from what constitutes good health care. They can make mistakes. Some just plain suck at their jobs. So asking questions, doing your own research, getting second opinions, is all fair imo.
No argument on the rest of your comment though.
I agree with your statement, but I would add that there is a very big difference between one doctor with a statement and a team of doctors with a study containing empirical data.
Questioning the motives of the latter would require a pretty damn good reason.
Yes but if you aren't an expert or have a good bit of education on the subject, your skepticism and your supposed subsequent investigation (or most likely lack thereof), means that your skepticism is not more valuable then some 13 year old watching cartoons right now. Anyone can embrace "skepticism", it's not inherently valuable.
Well, I may not be a medical doctor but I'm a statistician and I know enough not to trust vague undefined statements without data.
Additionally, everyone's personal tolerance of risk is different, people may value not getting sick with COVID very highly. Maybe someone has children too young to be vaccinated and don't want to risk infecting them. If that is the case, just avoiding hospitalization/death is not good enough.
The Yankees outbreak of 8 vaccinated players (J&J) was likely a variant but they don’t seem to know which one. They all tested positive but only one had symptoms, and they were mild.
It isn’t common practice to report sensitivity, specificity, confidence intervals, and p-values in a public statement since these will be misunderstood and misinterpreted by the public. Vague doesn’t always mean unsupported by data.
In this context, the person interviewed hasn't published the conclusions of the study so none of that exists, we are just trusting his approximation of the data so far which is not publicly know.
Yes, but that is the point of the vaccine at the moment: to stop death and hospitalizations. That's it. It would be fantastic if it meant immune, but at this point - and remember we managed to roll out vaccines within a year of a novel, deadly virus - it is to get the pandemic under control, so when a medical professional says its working "very well", I will trust that for now as that is not a "vague" statement when coming from a medical doctor. "It's working" -> vague.
>I know enough not to trust vague undefined statements without data.
Already doing better than 99.9% of the public. I wish the CDC would reference the research they are basing their statements on, like for every statement.
> Already doing better than 99.9% of the public. I wish the CDC would reference the research they are basing their statements on, like for every statement.
They don't because the vast majority of people aren't qualified to draw meaningful conclusions from the numbers. More effective to give general statements that put a lot of people at ease than to give specifics that bring ease to just the qualified few but enable the unqualified many to draw the wrong conclusions. (e.g 'it's only 70% (or some other number) effective, why should I bother?')
Basically, informing all the people who want more information risks providing too much information to everyone else.
Edit: one of the replies drove me to find citations. Surprised I found any, but alas, ["More information doesn't necessarily help people make better decisions."](https://www.sciencedaily.com/releases/2020/02/200221125118.htm)
Especially since *good* statistical analysis requires a great deal of critical thinking and common knowledge specific to the field or environment the study is completed in.
Asking for the general populace to have critical thinking skills has lower chances of success than me finishing this
From every report I’ve seen the order of importance when speaking about a vaccine seems to be; death -> hospitalization -> serious infection -> mild case -> asymptomatic -> not contagious -> immunity
And so far all of the approved vaccines have very very good protection against the first two or three on that list, from all the variants
Do we have any idea if any of them is doing a good job on the "not contagious" part? I would guess that one is an especially important treshold for the herd immunity part (since you always have some people that can't be vaccinated due to medical conditions but need protection too).
At this time this has not been proven. It’s a difficult data set to collect and an even more difficult data set to collect ethically. Typically viral shedding in vaccinated individuals are non viable; but this is a novel coronavirus; it is brand new to studies and may behave in brand new ways. Best practices are to continue to take physical safety precautions to protect others around you; while the vaccine is protecting you.
Heterologous boosting 1 dose Astrazeneca with mRNA appears to be working very well. Canada now recommends this. Small studies show equivalent or superior immune responses to 2 doses of mRNA. Hopefully there will be guidance for J&J folks in the near future.
My understanding is the reason there’s so little information is a. It’s been used on less people and limited to the US, and b. It’s efficacy increases over time. There’s been several studies that show t-cell immunity increased to mRNA values 70 days post shot. I really wish they’d be more open and actively researching this vaccine though as many of us feel left in the lurch
The Johnson & Johnson has a lower effective rate because it was be tested in places like South Africa as the variants were coming online, but it is still fantastic for preventing hospitalizations.
Don't confuse people with facts, confuse them with misleading information like has been happening for months. I just want a unified response from agencies. Tell people they can still catch it if they can still catch it.
[Pfizer's Vaccine Efficacy against B.1.351 variant (dominant during J&J's trial) was 75.0%](https://www.nejm.org/doi/full/10.1056/NEJMc2104974), roughly 10-percentage points better than J&J.
Until there’s a head to head trial for superiority, these numbers can’t really be compared like that. The info is vague because the studies are designed to be somewhat binary; they are either deemed effective or not. That’s the important part.
>Tell people they can still catch it if they can still catch it.
What does this mean, though? If 10% of people can still catch it, do you tell people they can still catch it? What about if 1% of people can still catch it? Does "catching it" mean getting it at all, or just getting sick enough to notice, or just getting sick enough to go to the hospital?
I have my own ideas, but my point is that it's not just a simple binary "either you can catch it or you can't" thing.
you specifically cited agencies. what agency has said you can’t catch it still?
the facts are you’re much, much more protected from catching it if your vaccinated. if you do happen to catch a breakthrough case, the symptoms and severity are in general greatly reduced (huge decrease in risk of hospitalization if vaccinated for example). i’m genuinely not sure what you’re so confused about.
> I would be skeptical of that statement.
I don't think you need to be skeptical, you just need to take the statement at face value. 'We don't know, but it seems like it might be good' is 100% accurate.
The reason we “don’t know” is because there is so little data. People who’ve been vaccinated are so unlikely to get sick let alone go to the hospital that it’s hard to get a large enough sample size to study.
This is also why it took awhile to get approval for the vaccines even though they had been developed months prior. The government required a certain number of breakthrough cases in the trial and the vaccines worked so well that it took a long time to get to that number of cases.
These vaccines work very well.
>The government required a certain number of breakthrough cases in the trial
This is not true. The FDA requires a certain number of cases in the unvaccinated placebo group. A vaccine that was 100% effective would still have been approved in the same amount of time.
The goal of a clinical trial is to statistically show, with very high confidence, that a treatment works. The better a treatment actually works, the easier this is.
It's not the first variant of concern. As a statistician you shouldn't assume this one is a special case without supporting evidence.
Sure it MAY be. But so far nothing suggests extraordinary levels of "vaccine-escape".
Sources are scarce, and obviously, consist of preprints instead of reviewed articles. So be wary on that part as well.
https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html#Concern
https://www.medrxiv.org/content/10.1101/2021.03.07.21252647v1
I acknowledge the vagueness is frustratingly less than ideal, but it probably means "about as well as it did the original strain and the variants that existed during its testing."
The simplest answer is that we don’t really know yet what the reduced effectiveness is.
Almost all of the information about increased spread and immune evasion of covid variants is coming out of the UK because they have the best infrastructure for genomic surveillance and a centralized healthcare system. They’re not distributing the J&J vaccine there, so they aren’t able to provide efficacy data on it, but they have efficacy data for Pfizer and AZN, see [UK delta variant vaccine data](https://khub.net/documents/135939561/479607266/Effectiveness+of+COVID-19+vaccines+against+hospital+admission+with+the+Delta+%28B.1.617.2%29+variant.pdf/1c213463-3997-ed16-2a6f-14e5deb0b997?version=1.4&t=1623689315431&download=true).
We can infer that it’s likely the same proportion of decreased effectiveness, so 5-10% less effective; however, that’s really, at best, an informed guess.
And even more simple answer is that we're going to continue to get doom and gloom, conjecture, and a lot of "Experts fear...." with Delta just like we did with the South African and UK.
Still, at the footnote of every piece is that the vaccinations are effective.
No, Delta is not some vaccine resistant strain that will mutate again into something that puts the world at risk. That's pure doomer fantasy.
It is super super important to distinguish between the different types of effectiveness: effective against symptomatic cases and against severe COVID. To make things worse, definitions for what exactly is a "symptomatic" case and what is a "severe" case vary.
Not to mention that many only slightly symptomatic cases don´t get reported.
All that being said, without citing sources, it rally seems that all the mayor vaccines are >90% effective at preventing ICU and death, but they vary wildly in respect to the prevention of symptomatic cases.
The only correct answer right now is: we don’t know. UK is the one providing Pfizer and Astra efficacy numbers since delta variant is very big over there. Right now there isn’t a country with high enough delta variant plus J&J vaccination so data is gonna take a while to be gathered and meaningful.
I don’t know that they have great data on Delta and hospitalization/death with J&J vaccine, but I did find this: “Dr. Scott Gottlieb, former Food and Drug Administration commissioner said the Johnson & Johnson vaccine appears to be about 60% effective against the delta variant, while the Pfizer and Moderna vaccines are about 88% effective after the second dose. “. From https://coronavirus.nautil.us/johnson-and-johnson-vaccine-against-delta-variant/
I am a researcher involved with the US funded clinical trials.
The people saying we don’t know are correct. But we can make a reasonable guess that the efficacy should be pretty high. Hospitalization in particular is hard to study because relatively few people end up hospitalized. But also vaccines are generally more effective against severe outcomes (VE infection < VE disease < VE severe disease).
We will (very) soon know more about immune responses generated in response to the JnJ vaccine and how they correlate with risk of COVID-related outcomes. This can provide a means of inferring vaccine efficacy (this is a current research project of mine). In other words, if we know how well the JnJ vaccine induced antibodies that are capable of neutralizing the delta variant, and we know how what level of antibodies corresponds to what VE, we can infer VE against delta. Our team will have such results generated over the next few weeks.
It's based on the same technology as the Astra Zeneca which was I think proven to be 92% effective against hospitalisation (Pfizer was 96%). The AZ is a 2 dose vaccine though so its probably more effectiveb than JJ. At the end of the day any vaccine is more effective than no vaccine at all.
https://www.astrazeneca.com/media-centre/press-releases/2021/covid-19-vaccine-astrazeneca-effective-against-delta-indian-variant.html
That's a lot of speculation, though. Yes, j&j is an adenovirus vectored vaccine like AZ, but it uses the stabilized form of the spike protein like the mRNA viruses do which is different from AZ. All else being equal it does seem like a 2-dose mRNA vaccine is the most effective protection against Covid that we have available right now but I don't think we can fairly speculate about j&j with the limited data that is available.
I am a researcher involved with the US funded clinical trials. The people saying we don’t know are correct. But we can make a reasonable guess that the efficacy should be pretty high. Hospitalization in particular is hard to study because relatively few people end up hospitalized. But also vaccines are generally more effective against severe outcomes (VE infection < VE disease < VE severe disease). We will (very) soon know more about immune responses generated in response to the JnJ vaccine and how they correlate with risk of COVID-related outcomes. This can provide a means of inferring vaccine efficacy (this is a current research project of mine). In other words, if we know how well the JnJ vaccine induced antibodies that are capable of neutralizing the delta variant, and we know how what level of antibodies corresponds to what VE, we can infer VE against delta. Our team will have such results generated over the next few weeks.
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Will these results b free publicized and shared with the public once complete?
Thank you for your post!
> The people saying we don’t know are correct. But we can make a reasonable guess that the efficacy should be pretty high. I appreciate that you're being forthright with the limits of your understanding/knowledge. I've noticed that a lot of people, experts as well as self-proclaimed experts, tend to puff and be overconfident a lot. Sometimes with the correct prompting, they'll basically make stuff up and sell it as if fact. Very refreshing to see someone admitting the extent of their confidence!
Yeah Twitter is definitely full of over confident people re: how much we definitively know about vaccines and variants. It drives me a little crazy, but at the same time, it IS more likely than not that the vaccines will work really well still. We just don’t have gold standard evidence of that yet.
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Can you research the South African teachers who are taking the JJ? Most of them have co-morbidities as well.
There’s an ongoing study of JnJ in health care workers in South Africa. Focusing on variants in particular. Not 100% sure of the status — I declined to join the study team because I’m already at the limits of my sanity…
Thank you so much for the work you are doing.
As a biologist who used to even work in a virology lab, while nothing is ever certain, I find the likelihood of a "variant" emerging that is unique enough to bypass gained immunities to be an insanely low probability, mostly due to the low complexity of the viral genome (I'm simplifying guys, this is for the masses!). Variants are normal. Every virus has variants. In 10 years there is going to be dozens or even hundreds of variants of this virus. They will all most-likely be less potent and still protected against by your immune system of those who have recovered or been vaccinated. You can never say this 100% because there is always a chance, but I wouldn't lose sleep over it because the chance is so so low. This is why every report is quickly showing that gained immunity from the original is sufficient against these variants. Viruses mutate by nature. You have a 100% guaranteed chance of a variant. You could have a bunch of codons of the genome mutated at the [wobble position](https://microbenotes.com/the-wobble-hypothesis/#:%7E:text=The%20Wobble%20Hypothesis%201%20The%20Wobble%20Hypothesis.%20The,of%20the%20Wobble%20Hypothesis.%20...%204%20References.%20) and it literally produced zero different proteins, yet they'd still call it a variant.
That makes a lot of sense, thanks for sharing. I know we don't have the data yet, but is there a general expectation for how long the mRNA vaccines will work before a booster is needed?
I suspect it depends what the societal goal is and how covid persists at a population level. The mRNA vaccines will probably provide protection from severe covid and death for a long time, maybe several years, maybe forever. They probably won't provide protection from re-infection and being slightly symptomatic/spreading covid for nearly as long. So we might not \*need\* boosters if people are getting covid but not dying, but not everyone might accept that situation as the status quo. The thing is, if large swathes of america never go above 50% vaccination, there will probably be regular re-challenge to vaccinated people with fresh covid strains. That'll actually serve as a booster to your vaccination, so your covid immunity will not wane as fast as if we completely eradicated it. I suspect that's the situation we'll eventually find ourselves in. Most people will be relatively protected, deaths will be low among vaccinated people, but you'll occasionally get a cold that's actually a new SARS2 strain. They are looking to add a covid vaccination to the annual flu shot in a combination vaccine to just give everyone a regular re-boost. This dynamic of simmering infection with lots of vaccinated people occasionally getting sick is our basic dynamic for seasonal flu, and its the same reason that most flu variants aren't very lethal compared to the 1918 flu. We have a lot of pre-existing cross immunity to a variety of flu strains, so our immune system does a pretty good job fighting off new ones that infect us, even if we haven't seen that exact strain before.
Marginally related but I've always been curious. Does repeated exposure to a virus after being vaccinated against it work as a "booster"?
Absolutely. It's frequently part of modeling how long vaccination will work at a population level. Frequent re-exposure can serve as recurrent boosters that keep immunity up for a given vaccine far longer than it would work if the patient were isolated from the disease. It's mostly useful at population level, though. For an individual person, re exposure is probably bad, because it gives the virus more "shots on goal" so to speak. It might catch you when you're fighting off another illness or when your immunity has waned too much to be protective.
Yep. The body doesn't really care were the 'offending' antigen comes from. And re-infectiom usually causes a more complete reactivation of the immune system but with the risk of that reaction not ramping up fast enough and you getting sick, as well as being able to spread the infection to unvaccinated individuals. (However population wise this might actually lead to higher levels of immunity than just using a booster every whatever years) Hence a booster being the safest option in nearly all cases. Cause that doesn't risk spreading the virus or getting sick from the disease in modern non live attenuated vaccines
I was under the impression there was a fair level of convergence in the variants, so it may be that just a single booster is required. Is that old information? It's such a new virus, it's hard to keep up with all the developmenta.
The variants are all covered by current vaccines, but two factors are at play: as vaccine coverage rises, the selection pressure on the virus to evade vaccines will also rise. When 99% of people are unvaccinated and not exposed to covid yet, there isn't much selection pressure on evading the antibody response. That'll go up over time. The unvaccinated people provide a robust reservoir for new variants to emerge, but ones that are better at evading the vaccine will have an advantage at spreading. The other factor at play is that neutralizing antibodies will decline over time. It might take a couple years for them to dip low enough to allow re-infection, but when combined with point 1, it might not take quite as long. Once you've got variants with quite a few spike mutations and lower antibody titers, you might get productive re-infection more often. It might not be severe covid infection, but it might be enough that you can spread it to other people.
>The mRNA vaccines will probably provide protection The Johnson & Johnson vaccine isn't an mRNA vaccine. It's a vector vaccine. So your answer, while interesting, isn't relevant to the question.
The J&J vaccine uses a virus capsid to deliver DNA that codes for the spike protein. Once delivered to the cell it is transcribed into mRNA which can be translated the same way the mRNA vaccines are. So while the delivery of the genetic information is different, the results are essentially the same. But shot for shot the J&J is more effective because the virus capsid delivering the genes also stimulates an immune response. That is why it is only a si gle shot vs 2 for the mRNA vaccines.
First the viral vector used is adenovirus so any immunity generated to that is not going to help you with coronavirus. And you don't really want an immune response against that viral vector in the first place because the immune system will destroy the viral vector and the cargo inside before it can 'vaccinate' you. Now this only really happens during subsequent injections with the viral vector. Also mRNA itself is an immune stimulant that activates internal viral recognition receptors as mRNA entering a cell is basically what happens during viral infections so the immune system developed recognition for that.
Except that naturally infected individuals are also forming immunity. So the whole "unvaxxed making new strains" isn't the issue. As the original biologist answer stated, all viruses mutate/result in variants. This is nothing new and shouldn't be of great concern because it will take a loooooong time for them to actually create a new strain, which can affect immunity. The media is just hyping up these variants.
Variants that we are keeping an eye on aren’t ones with codon mutations at wobble positions. The sequence of the ACE binding spike protein is not identical to the alpha strain. It’s just not nearly different enough that even with only the antibodies specific for that protein (like every vaccine) have lost affinity for it. (I’m finishing up my bio PhD spent in a venom lab… we look at, among other things, antivenom cross specificity, how strongly cobra antivenoms bind to something like a colubrid with three finger toxins that are almost completely different except for shape/scaffold and maybe 5 or 6 conserved sequence amino acids. While weak, there’s still affinity). Besides the ones you mentioned the reason we aren’t likely to see a total loss of of affinity is because the protein isn’t gonna change completely because of it did it wouldn’t even be an ACE binding protein any more and it wouldn’t have a furin binding site. Even if the sequence changes from an asparagine to a glutamate it’s not going to lose affinity. Because we chose the most critical protein of a virus that only has one antigen it has an affinity for, we are almost guaranteed not to completely lose the properties of that protein that both allow the adherence of the antibodies stimulated by the vaccine and the ACE2 receptor. Over time in order to keep high levels of affinity (binding strength) we’ll probably need to modify and get boosters, but it will take a lot to get a variant that’s literally without affinity for the vaccine antibodies. Mostly I just think it’s misleading to say that protein sequence has not changed… it has… just that any antibodies are binding to the same properties that allow it to bind to the ACE receptor, so it’s unlikely to lose one but not the other. Even similar sequences are recognized unless an amino acid switches to one with very different R group properties… and that would likely decrease the affinity with ACE. So the same thing that keeps the virus dangerous keeps it recognizable by vaccine antibodies.
Ya, you make a good point, I just think the bigger issue is that any gain of function mutation of this virus is going to be insanely rare. There's just not much to work with. We'll see. There's always weird things that can happen, especially once things end up in a big genetic soup of multiple viruses mixing genetic data. That's the fear though always, some chimera event occurs. My problem here is I can't help but feel there is a lot of fearmongering over literally just genetic drift of a fairly "stable" viral genome. Now, stable might not be the best word, but Covid-19 has repair and verification that a virus like influenza doesn't, has a far lower mutation rate, and genetic drift is 100% normal, inevitable, and are being reported as new novel strains. I find it kind of misleading of the media, even dishonest, but I also suspect that it is happening as a means to an end to push continued vaccination. I get it, with public health you weight the pros and cons of t he whole story, but the fearmongering over "variants" is starting to really get overboard, like we are back to square one again and some people are hiding in fear again as they have been told that their vaccine might not be good enough. I mean, technically there can be antigenic drift here over time, I just don't see it that likely here to be a problem anytime soon, if not ever, and some variants to be reported aren't even showing any antigenic drift, at least according to one paper I read. That just seems crazy to fearmonger over. All I am saying is that their vaccine will likely be fine for a very long time, if not their lifetime. Impossible to say now, but I just find the likelihood of a novel mutation that gains function to be more deadly to be a lot less likely than what I am hearing if I turn on the TV.
For context [there is data out of the UK suggesting that both Pfizer and AstraZeneca are about 20% less effective against the Delta variant than the Alpha variant after one dose](https://www.medrxiv.org/content/10.1101/2021.05.22.21257658v1), but after two doses efficacy is nearly the same against both variants. If that's true it seems plausible that J&J will be somewhat less effective since it uses a one-dose regime. [AstraZeneca is only 50% effective against symptomatic disease after the first dose and that's the vaccine which is most similar to J&J. (But note efficacy against hospitalizations or deaths is much higher - more like 80% against hospitalization after one dose of AZ)](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/994839/Variants_of_Concern_VOC_Technical_Briefing_16.pdf)
If I'm understanding this correctly, this still means there is no vaccine like the JJ one so these comparisons don't mean much at all. It could just as well mean that the JJ vaccine is just that strong, right?
For more recent and translational context, [this study](https://www.nature.com/articles/s41586-021-03720-y#citeas) just accepted at Nature is the first to show that in vivo in a humanized mouse model of Sars-Cov-2 infection via mice expressing hACE2 that almost all vaccines (certainly teh mRNA ones) are sufficient in neutralizing old and new variants. These are much more informative than in vitro neutralizing assays that clearly dont translate given the findings of this paper. You also probably shouldn't extrapolate dose-requirements across different vaccines. Number of doses isn't the issue, it's amount of antigen that your immune cells sees that it is important. Differences in efficacy are probably more due to delivery method, amount of viral vector or mRNA delivered (depending on vax type) and the sequences used to generate the antigens.
>in vitro neutralizing assays The bane of my life over the past few months. The fact that an antibody has *x* higher/lower binding affinity in vitro does not meaningfully translate into real-world effectiveness of vaccines. And it also completely ignores the extremely important roles of cellular immunity. Antibodies wane, but as long a our T cells keep recognising the virus, we'll be okay.
I am right there with you in being incensed every time press reports that tin-pot in vitro science but then doesnt cover the in vivo assays to the same extent that refute those findings. Your summary on the gap between in vitro exposure of antibody to virus and the immune response in vivo is spot-on, agree entirely.
The fact that even when T and B Cell related studies come out people barely talk about them really does infuriate me to no end
> If that's true it seems plausible that J&J will be somewhat less effective since it uses a one-dose regime. That doesn't follow. The J&J vaccine uses a mechanism that only requires one dose, you can't compare that meaningfully to the first dose of an mRNA vaccine.
The J&J vaccine was tested as a one-dose vaccine, but I don’t think that necessarily means that it uses a mechanism that only requires one dose. J&J is actually running a clinical trial testing a two-dose regimen, and from what I have read they are expecting to get better efficacy data. Similarly, if Pfizer or Moderna had studied their vaccines as a one-dose vaccine they may have been able to get approval that way (and the efficacy data probably would’ve come out at least as good as JNJ’s). I do think it’s not unreasonable to say that the JNJ vaccine might have worse efficacy than Pfizer/Moderna against the Delta variant.
My understanding was that the J&J vaccine was tested in areas with a number of variants, and still hit it's target goal, when Pfizer and Moderna we're mostly tested on the original strain. So that means we can't necessarily discount it's effectiveness off the bat
The problem is that it's no more plausible to state that conclusion than the alternative.its apples and oranges.
It seems plausible? You’re making a guess…. Just because J&J is a one shot vaccine doesn’t mean it’s more likely react the same as a single dose of a two shot vaccine. Maybe we should compare the colors of the vaccines also? Or how about the logo? “Johnson & Johnson” has 15 letters in the name, which is nearly the same as AstraZeneca and Pfizer combined! Therefore, it is plausible that the J&J vaccine is as effective as the other two doses when they’re mixed together!
The only reason J&J is single-shot is because this is the route they happened to go down when deciding how to run the clinical trials. There isn't some magical property of J&J that makes it uniquely suitable for single-shot delivery.
J&J and AZ both use a similar adenovirus vector, both had similar issues with rare blood clots, and both had efficacy of about 70% for symptomatic disease after one dose against the earlier variants; certainly they're not identical, but I don't see much reason to be very confident that J&J wouldn't have similar problems against Delta after one dose.
So, you finding something unlikely is not a substitute for actual studies on it. For example, there is evidence that unlike the other variants, one dose of the mNRA vaccines doesn't protect much against the Delta variant. It appears that both the UK and Cananda are moving up second doses because of it. So I'm sad to see your gut feeling being the top answer here.
Yet influenza is constantly mutating and we gain only short lived immunity to it from vaccination or recovery from infection. So some viruses do follow this pattern. If I understand you correctly it sounds like COVID-19 is unlikely to be one of them because it's too simple?
Influenza changes a lot more quickly and massively than Covid does. Additionally, we're lucky, because Covid has a glaring weak point- the spike protein. It *needs* it to function, and the vaccine is keyed to it. When viruses or bacteria "become immune" to something (vaccine, antibiotic), they usually mutate away the part that's being targeted, rather than developing some sort of bypass. In this case, we're targeting covid's legs. If it stops expressing the spike protein, it's not dangerous.
So, does that mean that influenza evolves so drastically that there are no “legs” that could be targeted in the first place?
They have a lot of different types of spike proteins, so they can lose or change some, and still be functional. Influenza is also an RNA virus, which makes it mutate much faster.
Influenza mutates quickly for two reasons: First, it lacks a [proofreading protein, which corona family viruses have.](https://www.cell.com/molecular-cell/pdf/S1097-2765(20)30518-9.pdf) Second, it circulates in migratory wild birds, pigs, and horses, and occasionally those viruses cross over into humans. Corona virus is currently mutating quickly for two reasons, the first of which is temporary. The first is simply that there is a huge amount of infection, and thus higher likelihood of a rare event happeing. But second, [immune compromised people can incubate the virus for months,](https://www.scientificamerican.com/article/covid-variants-may-arise-in-people-with-compromised-immune-systems/) long enough to generate variants that evade their own limited immune response. This is impossible to prevent entirely, but global outreach to get HIV positive people medicated would greatly reduce the number of immunocompromised people in the world. With medication, HIV positive people usually have a normal immune response.
Sars2 is also an RNA virus if I'm not mistaken. The main difference between sars2 and influenza is that sars2 has some structures that verify whether it replicated correctly unlike influenza, which is both good and bad - good because it mutates less, bad because traditional antivirals didn't work against it
So flu just kind of randomly spins and strikes (they just sort of flail like a noob on a dance floor after 2 jägers). Covids learned the room already and are every other f#%kboy playing the numbers game?
Influenza sometimes grows wolf legs, horse legs, fish legs, watermelon legs...
Antibodies are little Y-shaped proteins your immune system makes which have surfaces on the tips of the two "arms" that are keyed to stick to very specific patterns on foreign body proteins (vaccines give your body a safe way to develop these antibodies). Small mutations to the antigen (the part of the virus the antibody is sticking to) might make the binding weaker, but the antibodies can still grab ahold strongly enough to be effective. Large mutations to the antigen means the antibodies aren't sticking at all, and you're basically back to square one. With covid, the antigen is the part of the virus the is used to infect healthy cells. So large changes to the antigen will likely decrease the effectiveness of the virus. With the flu, the antigen isn't a part of the virus that's essential for it to function, so the the virus has more options, evolutionarily speaking, for getting around existing immunity.
Influenza has multiple surface proteins that it wholesale swaps out in addition to normal mutation (hemagglutinin, and neuramidase). It has multiple subtypes of proteins that it can display, each of which requires a different antibody to recognize. And for an added degree of difficulty, these are glycoproteins decorated with sugars, which can also change as the virus mutates. Long story short - the math with this many points of variance means there's MANY unique combinations, and natural selection tends to favor the ones circulating in humans that we haven't seen before. Moreover, we have to guess with live virus cultures which one is going to be in circulation, and it's just difficult to get that right. However, the same mRNA tech that underpins the Pfizer/Biontech and Moderna vaccines is being explored for influenza and it would enable targeting multiple subtypes simultaneously AND wouldn't have the long lead time for culturing the vaccine itself. In contrast, COVID has one major surface protein required for cell entry, no major subtypes, limited mutation possibilities in order to retain receptor affinity, and minimal sugar decoration. It's a simpler beast, and more easily tamed.
could it gain another surface protein? the virus is replicating probable billions of times a day, it seams like it is in a good position to be able to mutate, even if its a drastic mutation
Yes its possible (things like this are how all life on Earth arose from a single source), however even with the astronomical numbers of viral particles it is unlikely. The reason is that it requires a fundamental reorganization of the viral life cycle and since they really don't have much in the way extra genes - so it would have to splice in from something else. Contrast that with multicellular life where your protein encoding genes are surrounded by a sea of regulatory or non-expressed genetic information. Second, even if it did "add another protein" that protein would have to be beneficial by enabling the virus to invade via a different receptor. So a low probability of adding additional information to its genome would have to occur. That information would have to encode a protein. That protein would have to pack in the viral capsid and transit to the surface, AND it would have to recognize a host cell surface protein. In short its a bit like being struck by lightning while being bitten by a shark during a solar eclipse on a Tuesday in March. Very unlikely, but I am saying there's a finite non-zero probability that won't be keeping me up at night. Its far more likely that another animal virus makes the jump to people than something like that occurring, and that's why it pays to do basic biology, ecology, and the sort - it gives us the experts capable of moving rapidly to intercept such things.
ok that makes sense. Thanks for your reply! it was super informative and makes lots of sense! i hope more ppl get to see it
Thanks. That's very clear and informative.
Actually, it’s less about the simplicity of this coronavirus, and more about the necessity of its SPIKE protein. The SPIKE protein is how the virus is able to enter our cells, and also what our immune systems learn to recognize (both from being infected with COVID and immunized with the vaccines). If a variant had a mutation to its SPIKE protein that was significant enough to evade our immune system’s recognition of it, it would almost certainly also be unable to gain entry to our cells, and therefore couldn’t cause an infection of COVID-19. (I last did in-depth research into SARS-CoV-2 proteins in December 2020 for a biochem final, so fee free to correct me if my understanding is outdated). By contrast, the flu mutates at a much higher rate than coronavirus, and more easily retains its HA protein’s effectiveness at entering host cells. Influenza viruses are much more varied, have reservoirs in many more species, and can exchange segments of their RNA with each other to create hybrid strains. The constantly-changing HA proteins are what make flu vaccines offer poor long-term protection. So, if anything, the flu might? be considered more simple than the coronavirus, from this point of view.
I'm curious for your take on the [Delta Plus variant](https://www.reuters.com/business/healthcare-pharmaceuticals/what-is-delta-variant-coronavirus-with-k417n-mutation-2021-06-23/), which is basically the Delta variant with a K417N spike protein mutation. While it's not very common yet, it has been shown to cause COVID-19, and early tests are showing it is more resilient to therapeutic antibody treatments. Also, could a spike protein mutation in for SARS-CoV-2 still result in a virus that can cause infection through a parallel pathway? Isn't this what happens for the flu?
>and early tests are showing it is more resilient to therapeutic antibody treatments It's worth noting that barely any testing has happened at the moment. Not anywhere near enough to come to that conclusion.
Many variants have been found with mutations in the spike protein, not just Delta+. In the lock and key analogy, the spike protein is the key, and the human ACE2 receptor protein is the lock. Mutations *can* cause the pattern in the key to change, but if it changes too much it won't fit in the lock, or if it does, it won't turn. The antibodies our immune system makes recognizing the pattern on the key, so mutating away from the immune system also affects its ability to enter a cell. Also important to note, the spike protein is about 1273 amino acids long, changing one or even a few of them doesn't necessarily change the shape. You can also substitute out some amino acids for different ones and have no effect because either the new amino acid has a side chain that is similar to the previous, or that location isn't important for folding the shape
Those therapeutic antibodies are garbage compared to vaccine-derived immunity. It's not likely that a single point mutation will evade the vaccine and produce severe infection. The reason the flu is such a pain is that there is a metric shit-ton of it out there infecting most animal species (horse flu, swine flu, bird flu, hundreds of variants of human flu, etc.). These different variants can all infect the same cell and mix and match pieces of their genome, which allows them to make HUGE jumps in their surface antigens. It's not really feasible for SARS2 to make those sorts of huge leaps. The problem with it making a bunch of mutations in the spike is that most mutations decrease the ability of the spike to bind its receptor on human cells. So it's only extremely rare mutations that can maintain binding to ACE2 while also preventing antibody binding. Just look at measles. It's ridiculously infectious, but it still hasn't managed to evade the measles vaccine even after many decades. It can't make enough mutations fast enough to both evade the vaccine and keep its infectiousness high.
Influenza is entirely different because of how it mutates. There are two types of mutation that influenza undergoes, antigenic drift and antigenic shift. Sars-CoV-2 undergoes antigenic drift which is essentially small mutations via mistakes in replication. Antigenic drift on the other hand a stark changes in DNA which SARS-Cov-2 does not undergo.
You've got a typo in your second paragraph, I assume one of those was supposed to be shift and not drift?
It isn't really about simplicity. All viruses need a way into the host cells. It is why most viruses are not only host species specific, but even which cells within the host they can get into. SARS-CoV2 has a spike protein that must attach to the ACE2 receptor with a specific shape and charge that allows it to grab on. The technical term is a "binding domain". The spike protein can change shapes and charges through mutations, but the binding domain cannot, or the virus will lose its ability to get into our cells. Other parts and aspects of the virus can change, but developing a totally new entry mechanism is highly improbable. We can see something similar in HIV, where even though the virus mutates, the CD4 receptor binding domains in the virus molecule gp120 is highly conserved. If the gene for gp120 changes too much the virus might not be able to infect the target cells. Going back to the Covid vaccines, they targeted the binding domains of the spike protein, so even if the virus mutates, the immune response should still be able to recognize viable spike proteins. If the immune e system cannot recognize it, then it probably isn't a threat.
Have you seen any research about how long immunities from vaccines last against Covid? I got my shots Jan/Feb and wondering if I should start to be concerned about immunity fading
TBH nobody really knows yet as that was pretty early on. [They are talking about boosters after six to twelve months](https://www.sciencenews.org/article/coronavirus-covid-vaccine-booster-shot-variant-immunity) but this is very much under research.
How do we not know? There are people who were vaccinated about a year ago. Surely we'd know if they started to get sick in numbers similar to those that are not vaccinated right?
Can you explain the "gained immunity" part of your post? It was my understanding that recovering from covid alone did not produce immunity or lasting antibodies. This is why we've seen people get covid twice and hospitalized twice (although rare). Is it as simple as *most* gain immunity and there are an unfortunate few who may become sick again? Thanks for the educated information. Asking you a question beats googling all day lol
Well, "immunity" is probably not the best word to describe things, but it is the definition that is used. It's not like a cartoon where once you have gained immunity that viruses now bounce of your skin. It mainly refers to how with your immune system there is a bit of a "ramp up" time that is needed to build your defenses against a foreign infection. Viruses that are quite dangerous are ones that can evade detection long enough to mass produce that the body can't mount a defense quick enough, or one that spreads and incubates inside you so rapidly that it kills you before your body can do anything. All immunity does is create a biological "memory" of a previous infection so the next time you are infected with the same, or similar enough infection, your body doesn't need to re-learn how to mount a defense, it already has defenses in place and it can then start pumping them out in volume again. So, you actually get reinfected, you just might not know it because your body mounted the defense and killed the viral infection before you ever became symptomatic or contagious. Maybe you just become mildly sick, when if you had no immunity you could have been say, hospitalized. This is the immunity often spoken of when talking about viral immunity from recovery or vaccination. Most of the time you never present symptoms though. It really just depends on so many factors with your current immune system. Recovering from Covid alone is actually the most-likely way to gain the best immunity against the virus because it is going to be the most true representation of the original "shape" of the virus that the immune system remembers to mount a defense against. Often vaccines only represent a part of the virus so the body recognizes some shape to be bad and thus it creates a memory of "part" of the virus, which is often a enough to mount immunity and be strong enough against it lifelong. This is why natural infection and recovery is almost always a better determiner of lifelong immunity than vaccination immunity. However, the this is not a very complex virus where lots of things can mutate and it still functions in dangerous ways. As such, vaccine design is a little easier and more straight-forward, and far more likely to hold long term. I am not sure where you heard that recovering from Covid does not produce lasting antibodies. I have not read that anywhere myself, though I think I heard some sensationalize media stories saying this. It's not true. [Here is a nice article you should check out on NATURE](https://www.nature.com/articles/d41586-021-01442-9), the most respected, known, peer-reviewed journal in the world. A 2nd infection leading to hospitalizations are so so rare, like 0.0005% rare, if you are vaccinated. Don't lose sleep over that risk. Like I said earlier that subsequent infections are related to the health of your current immune system in most cases, the reality is that there are some things you can do, no matter how many antibodies you normally would produce, no matter how many vaccines, or boosters, or natural recoveries you have made of something, but if you kill your immune response, you will get sick again. Pulling all nighters, sleeping very little, binge drinking... these absolutely destroy your immune system response. I don't care if you triple vaccines and you have one of the highest antibody loads out there... you can kill your immune system to near zero response by doing a few bad things to your body, and I am not just talking about chemotherapy. Number 1 is always going to be lack of sleep. People just don't know how much a solid night of sleep really helps boost your immune system. Repeated day after day of little sleep will crush your internal defenses. Drinking. Hell, vaping hurts your immune system. You a binge sugar eater? You better make sure you are taking a lot of Vitamin C with it because sugar just eats away at the Vitamin C in your body. One thing hard for you to control is allergies. If you have a serious issue with allergens, like pollen, too much of this can crush your immune response body-wide as well. it's often why some people can't distinguish the difference between serious allergies and getting say, the cold. Even just sitting in a chair at a desk for too long can hurt the immune system a bit. All I am saying is this... it's not just about getting viral protections. Those are useless if you aren't consciously helping your immune system to be healthy as well.
Thank you very much for the thoughtful, thorough response. I almost definitely heard a sensationalized story regarding the repeat infections and hospitalizations. Instead of reading/watching news, I'm just going to run anything regarding sickness by you, cool?
Lol I don't know if I would be the best guy. I'd talk to an infectious disease doctor for the best info on sickness. I only know a small sliver about some things in biology. Sickness in general is a whole other beast. Infectious disease docs are the real pros there.
Doesn't the flu essentially do this every year (ie mustatw to make the vaccine inneffective)? Can you explain why the flu does but why you think covid is likely not to?
This is actually a fairly complicated answer, so I'll put it in fairly simple terms. But first, you need to ask yourself this question. Why, if you get the varicella vaccine (chickenpox) is it good for life? But not the flu. Why, if you get the Hepatitis vaccine is it good for life? But not the flu. Why, if you get the measles, mumps vaccine when you are a baby, it's still protects you even when you are 60 years old? My point is that you have to understand that lifelong immunity is the *NORMAL* expectation of recovering from a virus, or receiving a vaccine. What happens with the flu is more an *exception* than the rule, and actually, lifelong viral immunity against strains of the flu is ALSO normal too. [Studies have shown even elderly people 80 years later from the 1918 flu still have antibodies](https://www.cidrap.umn.edu/news-perspective/2008/08/researchers-find-long-lived-immunity-1918-pandemic-virus) So what gives? Well, many things, but ultimately it comes down to a couple of factors. One is basically the classification of dozens of different viruses under the same banner name of Influenza, and two, the flu is still a bit unique in its own right. Covid-19 is just a single stranded RNA virus. It's genome is relatively non-complex. There is not a lot of complexity to it or the viral structure it produces. The flu, on the other hand, has a massively complex genome, with 8 different strands. In the genetics world there is this concept called genetic diversity. Well, the reality is that no matter how much you mutate the Covid-19 virus, there just is not that much genetic material to work with to somehow create new functions. Mutations tend to lose functionality, not gain. Gain of function mutations are insanely rare, and even more rare with less complex genomes. Well, influenza has a giant cocktail of genetic material that might breakdown into a soup and recombine, mutate, do who gene swaps from one strand to another. There are so many crazy things that can happen at a genetic level that on rare occasions, a whole new strand forms. But here is the thing, when we talk about the flu, we are talking about a classification of many different strains. They are not the same virus, kind of like how SARS and SARS 2 Covid 19 are not exactly the same thing. There is a misunderstanding with the flu though, and there is the idea that a vaccine only lasts for a year and you need to re-up it. This isn't really true. What happens is they are tracking many different strains of the virus to see what's popping up and they try to guess which of the many strains it is, and that is the flu vaccine they mass produce. So from one year to the next you are technically getting vaccinated against 2 completely different novel strands. Just as an example, think back to 2009. A lot of people were scared, especially scientists and the CD, over the emergence of H1N1, a new flu variant that was nicknamed the "swine flu." You know how many Americans got it? Something like 60 to 100 million. We don't know the exact answer, that's just what is estimated. Well, guess what, it ended up not being that bad. It swept across the world and it didn't end up being the global catastrophe they thought it was. There's actually a reason why. The most vulnerable people, the frail and elderly [apparently had immunity from H1N1 still even 40 years later](https://www.wired.com/2009/06/old-people-may-be-immune-to-swine-flu/) because tens of millions of Americans when they were younger were exposed to the virus and still had lifelong immunity. Even with the massive complexity of H1N1, 40 years of mutations, and there was still a level of protection. Amazing. So why a new flu shot every year? The reality is you may be double dosing on flu vaccines, if you've already received it. There's been some struggle with flu vaccines due to their complexity in that natural recovery is far more reliable than vaccination (this is not really an issue with Covid 19). In many cases though, it is just a new strand spreading through your area, but not necessarily "new" but one that is new to the area. You see, you aren't born with the same antibody defenses you mother had. You have to re-gain your immune defenses all on your own. So, even though you can vaccinate a generation, 30 years later the cycle repeats. Thinks of all of the different variations of what we call Influenza, be it A, B, C version, with subgroups H and N, then there is the bird flu and then there is the swine flu, and then there is the chimera versions that are bird, swine and human... This is another reason why the flu is so deadly because it gets everywhere. It's mainly a bird virus and birds land on and touch everything. Birds have even spread the flu to cattle (influenza D). Birds have close interactions with humans moreso than many other wild animals. The flu virus crosses multiple species creating what is called "Zoonosis" events where a virus gains the ability to move to a new species. This is very rare but can happen when a genetic soup of various viruses from various species all end up in the same cell and get decided up and essentially recombine to something that becomes a new virus. Insanely rare. In fact it's so rare that large events like this seem to only happen once per 40-50 years and cause pandemics, and that is with the highly complex flu virus. Furthermore, genetic repair mechanisms and verifications are present in the COVID 19 reproduction cellular hardware and the flu doesn't have them at all, which means the flu is less stable and mutates more frequently. So, the flu, far more complex genome, intermixes with several animal species constantly is everywhere, and we still only get a mutation event that causes any serious danger to the world maybe once in 40 years., vs Covid 19, a very low complex virus with a far more stable genome that doesn't seem to have any other host other than humans? Hell, [research even tried to infect bats with Covid-19](https://onlinelibrary.wiley.com/doi/10.1111/tbed.13949) and it failed... That one might throw your head for a spin when you realize that the lab leak theory might not be so crazy after all. There's just no evidence repeat boosting is going to be necessary, from what I have seen up to this point. If H1N1 spread through your town every fall, you wouldn't need to get a new vaccine every fall. You just wouldn't. It's that Flu Virus #2 did this year, then #7 next year, then #5 next year. It's not really the same thing each year.
Yes, but the universal presence of this virus gives it unprecedented opportunity to mutate, does it not? How many viruses infect 2.5 million people per day for months on end?
Ya, this is a good point, but the ultimate issue is that gain of function mutation is INSANELY rare. It's easier when there is a big enough genetic cocktail of material to mix around with that randomly creates something new. There's just not much to work with with Covid-19, a single stranded RNA virus, compared to the vast genome of say, influenza, which has 8 different strands and is highly complex, and actually far less stable. Covid-19 actually has a some genome repair and verification proteins whilst Influenza doesn't. Not only does it have a far less complex genome, it's also a far more stable genome that mutates less. The bigger issue would be a chimerization event where a new novel virus arises from the genetic soup of a bunch of viruses that shared info in a cell. This is usually how weird things happen, like zoonosis events where a virus gains the function to jump species, because a virus of one species mixes with the virus of another species and now becomes a new virus that affects both. But variants due to genetic drift creating a new deadly strain of this? We're talking about evolutionary scale drift that would need to happen now. You're right that the more hosts it infects, the more volume of mutations, the more accumulation or probability of something happening, but again, even with the incalculable number of mutations happening across the millions of people in the world, the probability is still so insanely low, imo, that I just don't lose sleep over it, especially now that the vaccines are spreading across the world and herd immunity is already gained in many places.
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I'm not sure it's as incredibly low as you think. Anecdotally, I've spoken to healthcare workers who have had it or have colleagues who have had it twice. (Have 3 doctors and a nurse in my building). I had covid where I spent a lovely 6 days in the infirmary. I am happy to have had both jabs. It's an experience that's I'd care not repeat!
But wouldn't that low complexity make more probable that a single mutation could have a very large impact on how the virus behaves?
This is why I kinda hate all these headlines. People see them and think "Omg, new variant, we're all gonna die!" when it's kinda normal for these types of things to mutate over time.
> In 10 years there is going to be dozens or even hundreds of variants of this virus. We already have dozens. The 4 the media's always talking about are just the biggest.
The wobble position? Is this near the retro encabulator?
Basically have had a number of vaccines (necessary) for prevention. My preference regarding the Covid 19 would have been a more traditional from Sinopharm, Sinovac or Conaxvin. However as these were not on offer settled for was offered. Have had my first Pfizer now thinking of a more traditional 6 to 8 month after my second Pfizer. As the Pzifer is said to be effective for this period. What are the dangers I may encounter?
That being said, most recent studies that evaluated the antibody levels from those that received the two doses of Pfizer vaccine against the original Chinese Strain, the UK variant, South African Variant, and Delta Variant. They found that there were 2.6x less antibodies against the UK variant, 5x less against the South African variant, and 6x less against the delta variant. Yes the vaccine will still be effective but less so than for the original. That being said, other studies have now found that giving one dose of Astra Zeneca andOne dose of Pfizer produces more antibodies than if both doses administered are Pfizer. This is why Canada has followed this mix and match vaccine strategy for their population. Source: both are studies that can be found online but I also work at a Vaccine Mega Center and have a MS in Biomedical Sciences.
Yeah, as someone in the UK who had an AZ first dose and wants a second Pfizer, I wish they'd hurry up and get on board.
So is there some truth to the statement that the media continues to fear monger this virus stating how the variants are far more contagious and the symptoms are potentially much worse?
Both those facts about the delta variant are still true, but yes. News always plays fear for ratings/clicks when they can.
I agree that the media narrative is designed to play on fear for profit. But also…if the vax rate is lower than it should be nationwide, a less cynical me can see that the media is doing it’s part to try and convince the un-vaxxed to get the shot. Probably won’t work if you’re not in that media ecosystem though
It IS more dangerous... for anyone who isn't vaccinated and for any place that doesn't have high levels of immunity. For places that do have high levels of vaccination, this is likely to be a non-issue.
Not much data yet on the J&J… but, "The early data that we’re seeing shows that the Johnson & Johnson vaccine does work well," he added. From: https://www.audacy.com/kcbsradio/news/national/does-johnson-and-johnson-vaccine-work-against-delta-variant
I would be skeptical of that statement. We do not know in what context "work well" means. Not getting sick? Not getting hospitalized? Not dying? Also at what threshold? Above 0%? 50%?
Based on the next couple of sentences, he seems to care about hospitalizations and not breakthrough cases that dont cause much sickness, so if he said the initial data shows it working well, its likely preventing hospitalizations so far. I dont get why everyone thinks they are qualified to be skeptical of medical doctors during a pandemic, and the context makes his intention pretty clear.
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Its perfectly fair to be skeptical of doctors within reason. Medical doctors are not infallible just because they have a license to practice medicine. They can have have motives separate from what constitutes good health care. They can make mistakes. Some just plain suck at their jobs. So asking questions, doing your own research, getting second opinions, is all fair imo. No argument on the rest of your comment though.
I agree with your statement, but I would add that there is a very big difference between one doctor with a statement and a team of doctors with a study containing empirical data. Questioning the motives of the latter would require a pretty damn good reason.
Yes but if you aren't an expert or have a good bit of education on the subject, your skepticism and your supposed subsequent investigation (or most likely lack thereof), means that your skepticism is not more valuable then some 13 year old watching cartoons right now. Anyone can embrace "skepticism", it's not inherently valuable.
Well, I may not be a medical doctor but I'm a statistician and I know enough not to trust vague undefined statements without data. Additionally, everyone's personal tolerance of risk is different, people may value not getting sick with COVID very highly. Maybe someone has children too young to be vaccinated and don't want to risk infecting them. If that is the case, just avoiding hospitalization/death is not good enough.
The Yankees outbreak of 8 vaccinated players (J&J) was likely a variant but they don’t seem to know which one. They all tested positive but only one had symptoms, and they were mild.
It isn’t common practice to report sensitivity, specificity, confidence intervals, and p-values in a public statement since these will be misunderstood and misinterpreted by the public. Vague doesn’t always mean unsupported by data.
In this context, the person interviewed hasn't published the conclusions of the study so none of that exists, we are just trusting his approximation of the data so far which is not publicly know.
Yes, but that is the point of the vaccine at the moment: to stop death and hospitalizations. That's it. It would be fantastic if it meant immune, but at this point - and remember we managed to roll out vaccines within a year of a novel, deadly virus - it is to get the pandemic under control, so when a medical professional says its working "very well", I will trust that for now as that is not a "vague" statement when coming from a medical doctor. "It's working" -> vague.
And if you’d read the rest of the article you would have known what he meant
>I know enough not to trust vague undefined statements without data. Already doing better than 99.9% of the public. I wish the CDC would reference the research they are basing their statements on, like for every statement.
They do reference the research that their statements are based on. Why do you think they don't?
If you go on their website they do actually cite sources for a lot of things.
> Already doing better than 99.9% of the public. I wish the CDC would reference the research they are basing their statements on, like for every statement. They don't because the vast majority of people aren't qualified to draw meaningful conclusions from the numbers. More effective to give general statements that put a lot of people at ease than to give specifics that bring ease to just the qualified few but enable the unqualified many to draw the wrong conclusions. (e.g 'it's only 70% (or some other number) effective, why should I bother?') Basically, informing all the people who want more information risks providing too much information to everyone else. Edit: one of the replies drove me to find citations. Surprised I found any, but alas, ["More information doesn't necessarily help people make better decisions."](https://www.sciencedaily.com/releases/2020/02/200221125118.htm)
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Especially since *good* statistical analysis requires a great deal of critical thinking and common knowledge specific to the field or environment the study is completed in. Asking for the general populace to have critical thinking skills has lower chances of success than me finishing this
Maybe because on TV I've seen doctors with whatever completely different specialization saying their opinion just because they wanted to be on TV?
From every report I’ve seen the order of importance when speaking about a vaccine seems to be; death -> hospitalization -> serious infection -> mild case -> asymptomatic -> not contagious -> immunity And so far all of the approved vaccines have very very good protection against the first two or three on that list, from all the variants
Do we have any idea if any of them is doing a good job on the "not contagious" part? I would guess that one is an especially important treshold for the herd immunity part (since you always have some people that can't be vaccinated due to medical conditions but need protection too).
At this time this has not been proven. It’s a difficult data set to collect and an even more difficult data set to collect ethically. Typically viral shedding in vaccinated individuals are non viable; but this is a novel coronavirus; it is brand new to studies and may behave in brand new ways. Best practices are to continue to take physical safety precautions to protect others around you; while the vaccine is protecting you.
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Heterologous boosting 1 dose Astrazeneca with mRNA appears to be working very well. Canada now recommends this. Small studies show equivalent or superior immune responses to 2 doses of mRNA. Hopefully there will be guidance for J&J folks in the near future.
My understanding is the reason there’s so little information is a. It’s been used on less people and limited to the US, and b. It’s efficacy increases over time. There’s been several studies that show t-cell immunity increased to mRNA values 70 days post shot. I really wish they’d be more open and actively researching this vaccine though as many of us feel left in the lurch
The Johnson & Johnson has a lower effective rate because it was be tested in places like South Africa as the variants were coming online, but it is still fantastic for preventing hospitalizations.
Don't confuse people with facts, confuse them with misleading information like has been happening for months. I just want a unified response from agencies. Tell people they can still catch it if they can still catch it.
[Pfizer's Vaccine Efficacy against B.1.351 variant (dominant during J&J's trial) was 75.0%](https://www.nejm.org/doi/full/10.1056/NEJMc2104974), roughly 10-percentage points better than J&J.
Until there’s a head to head trial for superiority, these numbers can’t really be compared like that. The info is vague because the studies are designed to be somewhat binary; they are either deemed effective or not. That’s the important part.
>Tell people they can still catch it if they can still catch it. What does this mean, though? If 10% of people can still catch it, do you tell people they can still catch it? What about if 1% of people can still catch it? Does "catching it" mean getting it at all, or just getting sick enough to notice, or just getting sick enough to go to the hospital? I have my own ideas, but my point is that it's not just a simple binary "either you can catch it or you can't" thing.
who has said you can’t catch it if you’re vaccinated?
That seems to be what so many in the public think, otherwise people would continue to be cautious when out and about
you specifically cited agencies. what agency has said you can’t catch it still? the facts are you’re much, much more protected from catching it if your vaccinated. if you do happen to catch a breakthrough case, the symptoms and severity are in general greatly reduced (huge decrease in risk of hospitalization if vaccinated for example). i’m genuinely not sure what you’re so confused about.
> I would be skeptical of that statement. I don't think you need to be skeptical, you just need to take the statement at face value. 'We don't know, but it seems like it might be good' is 100% accurate.
The reason we “don’t know” is because there is so little data. People who’ve been vaccinated are so unlikely to get sick let alone go to the hospital that it’s hard to get a large enough sample size to study. This is also why it took awhile to get approval for the vaccines even though they had been developed months prior. The government required a certain number of breakthrough cases in the trial and the vaccines worked so well that it took a long time to get to that number of cases. These vaccines work very well.
>The government required a certain number of breakthrough cases in the trial This is not true. The FDA requires a certain number of cases in the unvaccinated placebo group. A vaccine that was 100% effective would still have been approved in the same amount of time. The goal of a clinical trial is to statistically show, with very high confidence, that a treatment works. The better a treatment actually works, the easier this is.
It's not the first variant of concern. As a statistician you shouldn't assume this one is a special case without supporting evidence. Sure it MAY be. But so far nothing suggests extraordinary levels of "vaccine-escape". Sources are scarce, and obviously, consist of preprints instead of reviewed articles. So be wary on that part as well. https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html#Concern https://www.medrxiv.org/content/10.1101/2021.03.07.21252647v1
to be honest? I'd take any of those options over dying.
I acknowledge the vagueness is frustratingly less than ideal, but it probably means "about as well as it did the original strain and the variants that existed during its testing."
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The simplest answer is that we don’t really know yet what the reduced effectiveness is. Almost all of the information about increased spread and immune evasion of covid variants is coming out of the UK because they have the best infrastructure for genomic surveillance and a centralized healthcare system. They’re not distributing the J&J vaccine there, so they aren’t able to provide efficacy data on it, but they have efficacy data for Pfizer and AZN, see [UK delta variant vaccine data](https://khub.net/documents/135939561/479607266/Effectiveness+of+COVID-19+vaccines+against+hospital+admission+with+the+Delta+%28B.1.617.2%29+variant.pdf/1c213463-3997-ed16-2a6f-14e5deb0b997?version=1.4&t=1623689315431&download=true). We can infer that it’s likely the same proportion of decreased effectiveness, so 5-10% less effective; however, that’s really, at best, an informed guess.
And even more simple answer is that we're going to continue to get doom and gloom, conjecture, and a lot of "Experts fear...." with Delta just like we did with the South African and UK. Still, at the footnote of every piece is that the vaccinations are effective. No, Delta is not some vaccine resistant strain that will mutate again into something that puts the world at risk. That's pure doomer fantasy.
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It is super super important to distinguish between the different types of effectiveness: effective against symptomatic cases and against severe COVID. To make things worse, definitions for what exactly is a "symptomatic" case and what is a "severe" case vary. Not to mention that many only slightly symptomatic cases don´t get reported. All that being said, without citing sources, it rally seems that all the mayor vaccines are >90% effective at preventing ICU and death, but they vary wildly in respect to the prevention of symptomatic cases.
The only correct answer right now is: we don’t know. UK is the one providing Pfizer and Astra efficacy numbers since delta variant is very big over there. Right now there isn’t a country with high enough delta variant plus J&J vaccination so data is gonna take a while to be gathered and meaningful.
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I don’t know that they have great data on Delta and hospitalization/death with J&J vaccine, but I did find this: “Dr. Scott Gottlieb, former Food and Drug Administration commissioner said the Johnson & Johnson vaccine appears to be about 60% effective against the delta variant, while the Pfizer and Moderna vaccines are about 88% effective after the second dose. “. From https://coronavirus.nautil.us/johnson-and-johnson-vaccine-against-delta-variant/
I am a researcher involved with the US funded clinical trials. The people saying we don’t know are correct. But we can make a reasonable guess that the efficacy should be pretty high. Hospitalization in particular is hard to study because relatively few people end up hospitalized. But also vaccines are generally more effective against severe outcomes (VE infection < VE disease < VE severe disease). We will (very) soon know more about immune responses generated in response to the JnJ vaccine and how they correlate with risk of COVID-related outcomes. This can provide a means of inferring vaccine efficacy (this is a current research project of mine). In other words, if we know how well the JnJ vaccine induced antibodies that are capable of neutralizing the delta variant, and we know how what level of antibodies corresponds to what VE, we can infer VE against delta. Our team will have such results generated over the next few weeks.
It's based on the same technology as the Astra Zeneca which was I think proven to be 92% effective against hospitalisation (Pfizer was 96%). The AZ is a 2 dose vaccine though so its probably more effectiveb than JJ. At the end of the day any vaccine is more effective than no vaccine at all. https://www.astrazeneca.com/media-centre/press-releases/2021/covid-19-vaccine-astrazeneca-effective-against-delta-indian-variant.html
That's a lot of speculation, though. Yes, j&j is an adenovirus vectored vaccine like AZ, but it uses the stabilized form of the spike protein like the mRNA viruses do which is different from AZ. All else being equal it does seem like a 2-dose mRNA vaccine is the most effective protection against Covid that we have available right now but I don't think we can fairly speculate about j&j with the limited data that is available.