Sadly, note that the study talked about here [1] is investigating the effect of the N501Y mutation, not the more worrying E484K mutation found in the South African 501.v2 strain that likely does escape antibody drugs and reduces neutralization by convalescent sera from past infections. [2]
For the vaccine to lose effectiveness, the mutation would have to drastically alter the spike protein of the virus.
This is effectively impossible as the virus is dependent on a functioning spike protein in order to infect cells, and the machinery involved with the mechanics of the spike are extremely delicate. Errant mutations that would cause compositional changes to the shape of the protein are almost guaranteed to cause functional failure. Using terminology, this is what we call a highly conserved area.
In both cases for the South African or UK strain, if you take a look at the areas where mutations have occurred, you’ll see that the code responsible for generating the spike protein is basically completely unaffected. This will generally hold true for any successive future strains.
This doesn't make much sense to me, given that coronaviruses, with spike proteins, have existed for eons, and humans have had lots of time to build up immunity to previous coronaviruses (ones that cause colds, for example). So there was something about the Covid-19 coronavirus spike proteins that was different enough where it didn't look like "familiar" coronaviruses, so I see no reason why it couldn't evolve further to evade whatever antibodies humans are able to build up to the vaccines.
You can make multiple spike proteins that target the same receptor.
This generally happens when a virus from another animal (and thus with a slightly different version of the receptor) adapts to humans.
Basically, a gradient descent from a very different starting point ending up in a different local minima.
The question is, is the spike protein at a local minima (very probably quite close to it), and could it jump to another local minima then? Most likely not.
It's possible it will evolve to make our antibodies slightly less effective, likely as a trade off for infectiousness, but incredibly unlikely the spike protein would evolve to be unrecognizable to our immune systems. Historically, this doesn't happen all that often, except for viruses with chronic infections over years that can do a deeper search over the gradient, but even then it generally takes years to decades.
Given the non-linear dynamics that proteins must live under, I like the usage of local minima as an analogy. It feels apt.
Generally though, within the context of machine learning, one of the benefits of gradient descent, especially when stochastic, is that we can get past those local minima humps. Does this hold less true with respect to the process of sequence mutation that viruses go through?
Another way how to characterize the "context of [deep] machine learning" is that it is the regime of high temperature
(stochasticity) as a result of small batches and/or large learning rates, and/or the regime of high momentum (Adam et al.). The evolutionary dynamics in the genetic space is (intuitively) at much lower temperature (shorter jumps) and with no momentum (because of the evolutionary pressure).
The difference in viruses is that if you get on the hump, you are outcompeted by other viruses that stayed in the minimum, which makes it a lot more difficult.
you are speaking about a general case scenario, there is conservation of sequence region and variation of sequence region. to wit one protien encoding sequence has separate regions corresponding to regions of the product protien, the receptor binding domain[RBD] is a moderately conserved region ; the ImmunoAntigenic regions are not tightly linked to the protiens receptor binding function thus may vary at a greater rate than the RBD regions
This isn't correct. The constraints placed upon epitopes by the cell receptor vs antibodies aren't the same. Rhinoviruses and Influenza viruses escape past immunity without fundamentally altering their biology all the time!
The 2nd paper cited does in fact show functional virus with a charge-shifting E->K mutation in its receptor binding domain that escape many antibodies raised against earlier strains.
I used to engineer viruses and human immune cells for a living - maybe read a little more virology/immunology.
While that may be true, I think that scale plays a role here.
The ancestors of this virus were bouncing around between a relatively small set of humans and animals for a while before becoming SARS-CoV-2.
Now with a significant portion of the world infected, it does not seem unreasonable that it would mutate. Although at that point it probably would not be considered the same virus anymore.
Am I reading the second paper correctly when I say this was conducted on a sample size of 11, and they found that the E484K mutation had saw no reduction in neutralization in some of those subjects? I’m trying to get a better sense of the numbers involved to figure out how much credence to lend to the dangers posed by the second mutation.
It's unlikely to _completely_ escape immunity - humans will raise antibodies against different regions of the spike protein, but it does seem to confer a pretty significant average resistance to patient sera. There's another study looking specifically at several different monoclonal antibodies against this mutation at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723407/
No idea why the downvotes here (at initial time of writing), that’s literally how the immune system functions, it’s a random process and everybody’s antibody DNA will be different to someone else’s antibody sequence against the same antigen.
No vaccine is training the body on the exact antibody to raise, it’s training it to (hopefully, because sometimes the stochastic process missed) recognise particular epitopes.
Important to also note that generally (and particularly during early infection) there will be many antibodies that recognise parts of an antigen.
Affinity Maturation through somatic hypermutation is one of the most amazing processes the body does - look it up or for a very brief summary look at my notes on page 32 (or the whole mechanism of adaptive immunity from 27) with a little diagram on page 28
It truly is. In early medschool we had a group student session on the adaptive immune system where we had to brainstorm on antibody generation and nobody in the group even came up with an idea remotely close to how it actually works. Robust and amazing. Talk about brute-force searching.
Still, at this day my hope is that we'll be able to do the body's work even better at some point using computer designed antibodies (or similar) at least for therapies. There are some notable bottlenecks in the adaptive system where antigen fragments have to be broken down and shown to potential antibodies and this is a bit different between humans etc. The human antibody molecule is also very large and it's particular design doesn't fit some epitopes you'd want to hit (not an expert on it but I remember one of the HIV proteins having an area you'd want to train on but that can't accommodate the antibody variable fragments well).
When you say average here, is that in the sense of average resistance over time for a given patient or average resistance across a population? The paper seemed to imply a great deal of heterogeneity in individual responses to the variant, so significant average would just be something like part of the population affected very badly, another part not at all, vs everyone affected mildly?
Averaged over a population - some people will have resistant sera and others not depending on the parts of sars-cov-2 targeted by their polyvalent antibody response. Note that this is only looking at antibodies, not T-cell responses... so the clinical consequences are harder to predict, but it's certainly a bit concerning.
Say that Pfizer were able to simulate 50 possible mutations and put all of them into a single vaccine, would there be any risk that the antibodies could interact with each other in some way that makes the vaccines less effective?
Also another scenario: say that we get yearly Covid shots that contain the latest strains, would these accumulate over the years and start interacting with each other?
As I understand it, the second isn’t an issue so 50 vaccines over 50 years would be fine, that’s how seasonal flu vaccines are done.
The first is mostly a question of how similar they are. Best case original vaccine covers all strains without modification, worst case you need 50 different vaccines. But the most likely combination is a mix where you might need say 5 vaccines, each of which over an overlapping subset of the 50 strains to various degrees of effectiveness.
The immune system presumably has a limited capacity of circulating antibodies. By introducing new antibodies, do we reduce the amount of previous antibodies, and does this reduce their immune response? Is there a concept or metric of "antibody dilution"?
While correlation is not causation, I find it interesting that the human immune system only remembers the common cold and seasonal influenza for several months, but diseases like the polio for much longer.
Viruses are typically rapidly mutating so you should consider them to be a fuzzy statistical ensemble around the "official" sequence, even in one patient. Therefore these viruses can facilely jump over hills in the gradient descent of optimization; but keep in mind optimization is not just a one-factor thing. If you are interested in this the keyword is "viral metagenome"
An E to K mutation converts a surface negative charge to a surface positive charge. So if your antibodies were expecting a negative charge and therefore putting positive charges near that place when they attach to the virus, the polarity on the mutant has now shifted and the antibodies will be repelled from the mutant virus.
The majority of viruses do not mutate rapidly enough to evade immunity. The exceptions are virus with chronic infections because they can mutate much more easily, and some viruses like Influenza that can use antigenic shifts.
It's really not typical. Even in all of the human cold coronaviruses, only one seems to be evolving its spike protein, and it does so quite slowly.
If it was typical, we wouldn't see the amazing efficacy of vaccines against endemic diseases.
> Therefore these viruses can facilely jump over hills in the gradient descent of optimization
It warms to see that the similarities of some aspects of biological life to the current AI/ML terms has entered the lexicon, well at least on HN crowd. The fact that it makes a lot of sense to use those terms hints that we might indeed be on the right track to building AGI and understnding the life itself in general.
Objective cost surfaces have been around way longer than ml. It's been in the genetic algorithm lexicon for a long time, and more true to form, in stuff like actual potential energy diagrams of high dimensional degrees of freedom spaces in enzymology. Also having been a professional biochemist and worked in AI infrastructure, I know the commonalities well and know how to avoid faux-amis.
Note that this process is NOT backpropagation.
"The fact that it makes a lot of sense to use those terms hints that we might indeed be on the right track to building AGI and understnding the life itself in general"
Nope, it's a residual of the fact that AI stole ideas from other fields, and ran with the terminology as marketing. Sometimes even to the point of extreme divergence from the original ("neural" nets).
How is there gradient descent or even a gradient in biological mutations? If anything there could be an analogy to undirected trial & error as in genetic algorithms.
Gradient descent is a subset of survival of the fittest, described by Darwin in 1800-1900, and has been in applied in computer science since the 70's. An AGI will probably use some form of gradient descent during its training, yes, but I wouldn't argue that this has brought us even close to an AGI.
It’s just evolution - we put social distancing and masks in place, so variants that can overcome those emerged and spread.
Think of it like antibiotic resistance - our crappy attempt at lockdown was like not finishing the course. We gave it loads of places to multiply but didn’t finish it off so it just adapted
The mutations don’t arise because of selection pressure against masks and social distancing, that is dangerously wrong. They arise in an individual patient who has a poor immune response who can’t clear the virus for a long time. As their immune response tries to clear the virus it adapts to be more effective over many generations inside that patient. That’s why we have distinct lineages, each of these variants with multiple distinct mutations probably arose in a single person.
An N to Y mutation is associated with tighter specificity in binding protein protein interfaces. An E to K mutation is changing the surface charge from negative to positive so it shouldn't be surprising that it reduces antibody's ability to recognize, assuming it's in the most recognized pocket. Hopefully this will be a relatively easy cut and paste into the existing vaccine cassette if it turns out to spread really widely.
I'm far more worried about the FDA and logistics than technical limitations.
Even if you could make this fix in a day, it'll take months to get FDA approval, and then you still have to manufacture and distribute it. And by that time the populous will have gotten immunity the old fashion way.
Indeed. And the likelihood of escape are worse the greater the infected population x time to new vaccine. I'm increasingly worried that covid-19 is the slow loris of viruses. Too slow and mild to warrant panic-mode measures (I don't mean lockdowns), just gonna be an annual millimation of the population.
Aren't we in panic mode measures already? I'm not sure there's much more most countries can realistically implement even if there's a 10x more lethal variant.
During initial containment china welded apartments shut and organized essentials deliveries by dedicated couriers for each city block. And then there's the option of military-enforced cordons. There are multiple levels of panic left untapped.
That's why I said "most countries", because in (say) the US the government couldn't pull that off even if they tried. (For one thing, it's hard to weld shut suburban housing.)
Perhaps, but if the virus was as transmissible as sars-cov-2, but had a much higher fatality rate (say 60% like Ebola). Then you would get a lot more support for strict measures amongst the general population.
Both the South African and UK variant seem to be under the name 501Y.V2 but the South African version has a mutation not seen in the UK strain:
> The variant in South Africa carries two other mutations in the spike protein (E484K and K417N, among others) which are not present in the U.K. strain
This three day old article also anticipated this study results:
> While scientists believe the U.K. variant is not likely to affect the efficacy of the vaccines currently being rolled out in the West, there is more uncertainty regarding the other strain.
I’m guessing they are both of the same “strain” but of different “variant”. But I don’t know enough about how virus taxonomy works to validate that. Sounds like two levels of mutation...
The first paper describes the effect of mRNA based vaccine derived serum on both variants, showing that both variants are affected about equally by the vaccine, if I’m not horribly mistaken?
What I meant by sera above was general adaptive immunity. It's likely to partially resist past immunity from both vaccines (esp. from the spike-only vaccines: moderna, pfizer, etc) and natural infections from older strains. We'll probably know a lot more about it soon, but we may need to update our vaccines to include this mutant class.
Does this mean there's now a variant that is immune to all the vaccines, and we're basically back at square one with the pandemic?!?! :( or am I misunderstanding? Is it still protected against from mRNA vaccines, but just not prevented by immunity from past infections?
Not square one. It’s unlikely there would be 0% efficacy. But it could be less.
But also not square one because it takes literally a day to redesign mrna vaccines for new variants. Then hopefully they can be approved faster the second go and manufactured/distributed more quickly.
But I’d say all northern hemisphere countries should do their best to focus on local elimination in summer 2021. Most of europe had it in reach summer 2020 but decided to reopen early and keep the virus at a low level.
That was an abject failure. It probably only would have taken another month of heavy restrictions to eliminate.
The mutations we’re seeing in the winter of high case volumes caution against doing another cycle like this.
> But I’d say all northern hemisphere countries should do their best to focus on local elimination in summer 2021.
This isn’t realistic. Fatigue with COVID restrictions has already set in across Europe: people are wearing masks in sloppy ways (not covering the nose, or even just putting the mask over their chin) and returning to socializing or even leisure travel. The authorities know this, and while they can do things like keep restaurants and theatres closed, they appear to feel little democratic mandate for using the police to enforce strict social separation between individuals. And that is in the winter: once the warm weather comes back, expect even more flaunting of restrictions.
That happened summer 2020 and look where things ended up. There are a few factors I think you’re missing:
1. The virus is seasonal. Substantially less restrictions are needed over the summer. Outdoor socialization really isn’t high risk
2. School is out. This naturally lowers spread
3. A bunch of people will be vaccinated. This will surely make it easier
4. We’ll probably have new rapid tests by the summer. They go a long way to reducing spread without much inconvenience. Michael Mina has been banging his head against the wall for months to get people to listen: these can be as effective as lockdowns and much less burdensome.
5. At least some countries will figure this out, go for elimination, and require a vaccine/negative test for entry and make travel arrangements with other covid zero areas
Now it might be the vaccines work perfectly, no mutant strains escape them, and we won’t have a repeat of this in fall/winter 2021/22.
But if that scenario does seem likely them elimination is overwhelmingly the best option. And society that can’t pull itself together to do that will live in a purgatory.
> 4. We’ll probably have new rapid tests by the summer. They go a long way to reducing spread without much inconvenience. Michael Mina has been banging his head against the wall for months to get people to listen: these can be as effective as lockdowns and much less burdensome.
The “inconvenience” in the USA (besides outright coronavirus deniers and people who flout restrictions in contempt of expert and professional public health officials) is that there is no guaranteed paid sick/isolation leave if one is ordered to go into isolation. Given that 40% of Americans have less than $400 for a “rainy day”, going to work while sick may be necessary. Also, in a lot of cases, no job: no health insurance, which is tragic and consequential during a pandemic.
You also need to have a strong public health system in place well in advance, where citizens already have been following and adhering to prevention programs for a long time, along with trust in the system. The EU countries generally do better with this, in the most general sense, but it depends on the country. For example, there are published reports of what percent of the country’s population washes their hands every time after they use the restroom. Some of the more “eastern” EU countries (which are now westernized) do way better that west/north Europe.
Also, some countries routinely issue self-isolation orders for 14 days, and the police will check, multiple times. In some countries these fines are over $1,200 for the first offense, and for the second offense, it’s $20,000. Both of these fines are unaffordable for the majority of the population.
Anyways, my point is that rapid self tests do work, but it requires a properly functioning government, with a strong public health system, and a cooperative public that trusts their officials and adheres to public health recommendations well before a pandemic occurs.
This is true about the US. Nonetheless, every day people need to be hospitalized with covid or stay home because they’re too sick to work.
So over the long run there’s much more turmoil of the type you speak of. But I agree the US needs a better system for letting the contagious stay home.
Perfect needn’t be the enemy of the good though. If, say, 45% of people could isolate, then having them know they’re positive could help too.
That was very much the opinion of the immunologists I have been reading the opinions of recently. Giving this virus opportunity to mutate through allowing circulation is playing with fire next to a dynamite factory.
> Everywhere should've pursued elimination strategy like Australia and New Zealand
Australia and New Zealand were very unusual in having that possibility, not everyone could have followed such a strategy. The EU had to move thousands and thousands of migrant agricultural workers from Eastern Europe to Western Europe for the harvests, otherwise there would have been scarcities of common foodstuffs. Also goods move through Europe largely through freight trucks that mean drivers moving about, not container shipping like the two island nations you mention.
I’m in Atlantic Canada, where we had eliminated it locally. We moved in agricultural workers, it was fine. We just had an isolation requirement and testing.
We have freight trucks from the US too! A lot of obstacles are not, in fact, insurmountable. The actual issue is that most places weren’t aiming at elimination.
> We moved in agricultural workers, it was fine. We just had an isolation requirement and testing.
As you might remember, there was a shortage of tests the first time that the EU needed to move its agricultural workers en masse (which happened already in the spring – harvests in Spain are more or less continuous, unlike Atlantic Canada where it is much more restricted seasonally). Also, many of those agricultural laborers live in precarious working conditions that the state has little insight into, and arranging any kind of isolation on short notice was not possible.
The EU was not aiming at total elimination because the virus had already spread throughout the bloc practically before the authorities were even aware of it and again, these are not island nations.
Sure but you had until the end of August to end it. Spring was the early days. And it would have been conceivable to try to eliminate it locally in sectors other than agriculture. Deal with the easy buts first and then the hard bits after. Often the hard bits become easier in so doing.
You could have kept internal border controls except for essential work. We did that in Atlantic Canada. Australian states did that. We’re just as integrated as the EU is! We never had a border at any point in our history. So we set one up.
There are non islands that more or less eliminated it. China, vietnam for example.
Harder in the EU? More complicated? Absolutely. But the policy the EU pursued was an abject failure, so merely saying “there would have been difficulties” doesn’t show that elimination would have been worse. The places that reduced covid better generally saw better economic results too.
> You could have kept internal border controls except for essential work.
Lack of internal borders in the EU is one of the most important features of the bloc, both in terms of maintaining close integration that could prevent more intra-European wars and in terms of mere everyday convenience. I would gladly sacrifice the demographic most at risk of COVID (about half of all deaths in the EU so far have been in care homes) in order to avoid internal borders.
Also, China has been able to eliminate COVID (and even that is subject to doubt) only through civil-rights violations that the West would not tolerate. Pointing to China and saying "They did it, so the EU could too" misses the point. Vietnam was able to avoid a surge in COVID cases only because they hadn’t yet got the huge number of cases that the EU had first without even being aware of it; of course if somewhere else is already suffering, and you aren’t, you can close the borders and avoid the problems from the start.
From what I've gathered, it's more like: It's likely that the vaccine will have reduced efficacy (seen over the whole population) against this new strain.
That's because your immune system essentially learns to recognize a random part of the virus, and if it ends up "training" itself using that part of the spike protein that's changed in this strain, it won't detect the virus.
The bigger question I have is when will we be ready to confidently claim that the vaccine doesn’t just prevent symptoms but also prevents spread? (Edit: at the same or nearly the same 95% rate)
I can’t see a human trial being able to show this, and contact tracing is overall so poor how long will we have to wait to not see a case that can be tracked back to a vaccinated individual before we are willing to agree that the vaccine is highly effective at stopping transmission?
For example, by Feb 1 we will have millions of people who are effectively protected at least from symptoms due to vaccine. So e.g. by March 1, if we have no, or single digit, reported cases of 2-week post-jab transmission?
The corollary is how durable is the effect?
To fully reopen the economy you need some kind of consensus on where the truth lies to these two questions.
I wonder if public health agencies will never really admit, but just the case count will start to dwindle and mitigations will start to lessen, without ever really coming out and admitting vaccinated people don’t need mitigations 2-weeks-post-jab.
Similar to how we’ve never really admitted that people who’ve had COVID are immune and can no longer spread it.
I think fundamentally gov’t is too afraid of having two classes of citizens, and mainly, that one class (the antibody negative class) lying that they are actually the other.
Reopening the economy or not is a political choice and doesn't necessarily depend on vaccine effectiveness. The economy in Florida has been pretty much open since September. We can argue about whether that is wise but the reality is they are open today.
There’s truth to this, but it’s more complicated. In my neighborhood, even if our mayor “opened” things back up, very few would be willing to, say, dine indoors. I can say this confidently because we were less locked down in the late summer.
But I agree this can depend on the community. I even specified neighborhood rather than city because I'd imagine this is different in other neighborhoods in my own city.
Which scientific research? That which only takes the virus related deaths into account, or that which balances other factors such as depression, suicide, substance and spousal abuse, and long term economic factors?
Israel has managed to give the first shot to 20% of its population, and at this rate will be into herd immunity territory by the end of the month.
As far as pressures on healthcare systems though, once over 65s have been vaccinated (and the northern winter ends) the pressures pretty much vanish.
> Similar to how we’ve never really admitted that people who’ve had COVID are immune and can no longer spread it.
Well we don't know that. In many cases the virus reproduces and spreads without any symptoms. If the spread occurs before the immune system kicks in you could still be a carrier even though the vaccine makes your symptoms pretty much zero.
> Well we don't know that. In many cases the virus reproduces and spreads without any symptoms.
We know that asymptomatic people who are not immune can possibly spread the virus. But that’s a slightly different question.
We know that it’s very rare for someone with antibodies to be symptomatically reinfected with COVID. That’s also a slightly different question.
The specific question on the likelihood of someone with natural immunity to be able to later spread COVID without a symptomatic infection;
I’ve never heard of a single confirmed case of this happening. And the point is not that it never happens, the point is it’s a negligible risk. Smaller than, for example, someone who isn’t immune who is wearing a mask.
But from a public policy perspective, we’ll never actually admit this, just because the second order effects — where some people can rightfully walk around without a mask and are rightfully not subject to mitigations and lockdowns - are political untenable.
In antebellum New Orleans, people would often try to get infected with yellow fever as soon as they got here to get it over with so if they survived they could claim immunity.
"once winter ends" I've been wondering about that. In June things were just great, but at the same time our health agency (RIVM) claims COVID-19 is not affected by seasons. Are they lying (since they're saying "is not" instead of "might not" / "unknown"), or was what happened around June a coincidence?
“It’s not seasonal” is one of the mantras health agencies repeated in february, along with “masks aren’t shown to work” and “it doesn’t” spread by aerosol.
My guess is your health agency simply hasn’t re-examined their beliefs as evidence came in.
I can't believe it is not a bit seasonal, whatever the reason is.
First wave ended in June in the northern hemisphere and started in the southern hemisphere at about the same time. We are seeing a similar shift in the second wave.
It can be a coincidence but since people are more likely to stay inside when it is cold outside, and transmission is more likely inside, it makes sense.
From the phase 3 trials you'd absolutely expect cases to occur after vaccinations. That's what the 95% efficacy after 2 doses means, that 5% of people had symptomatic infections.
Hopefully it is the case that the 5% are people that have a weak response to the vaccine and the remainder mostly aren't infectious. They can study this by monitoring for asymptomatic infections (I don't know if they are going to or not).
95% effectiveness does not mean 5% of people had symptomatic infections. It means there were 20 times more infections in the placebo group compared to control.
If you gave the vaccine to 1000 people and placebo to 1000 people, and 100 of the placebo and 5 of the treatment group got sick, that's 95% effective, as is if all 1000 in the control group got COVID and only 50 in the treatment group.
None of the data you'd need to have policies based on calculated immunity is going to come quickly, if at all.
I don't think it's reasonable to try to run an open economy for those who are likely immune and a parallel economy for those who are unknown. There's no way anyone can verify any of that in a day to day setting.
I would expect that some international borders might reduce quarantine requirements if you can show evidence of probable immunity, but not right away.
That intuitively doesn't make sense for the fact that vaccines help produce antibodies which prevent the virus from spreading within the body and reproducing within the body. The spike protein is detected as something bad, and the body becomes furious and destroys the whole shebang, but not before binding to the spike protein as well and preventing it from infecting cells. If there's a lower viral load in the body, then it reduces the chance of spread (hint, because viral shedding is what causes spread across people).
As I said, my contacts in the medical field have the same opinion as the article. It's "unknown" officially, but apparently people on HN don't know anyone in the field who is literally on the front lines researching this. The overwhelming opinion (articles aren't being written yet, expect some in a few weeks) is that the Pfizer vaccine does not actually prevent spread of the virus, only symptoms which decreases the probability of spread, but does not completely prevent spread.
It does not prevent the virus from spreading
It does not protect against certain variations that we are seeing like in South Africa
This means that the pandemic will still be there next winter some how. Likely not as bad as it is now. But it won't be over yet as a thread for societies. Remember most emerging/developing countries are not expected to receive vaccinations any time soon.
They'll be able to update the vaccination but many people will lose trust in them unfortunately
Means that our economies & currencies will be in trouble
Remote work will break through. After 2 years nobody is used to anything else anymore
Many people will permanently lose their job/business, but software companies will continue to do extremely well (although there will be some regulatory crack down on the largest companies)
The article is asking the wrong question (Immune but infectious: Can someone vaccinated against COVID-19 still spread the virus?). The question is not whether or not, but to which degree. That is, how likely are they to spread the disease, how many people do they infect on average, how much virus do they shed...
This is not true, the Pfizer vaccine does not prevent you from carrying the virus and spreading it to others who do not have the vaccine. This is what a medical professional told me who was required to get the vaccine. Their entire department had to get vaccinated (Pfizer, not Moderna) and they are still required to wear masks for this very reason. Do your research.
I don't mean this abrasively but, referring to an unknown third party for credibility and then telling people to do their research does not seem overly convincing to me.
This is the right conclusion, but for the wrong reasons. A vaccine which induces antibodies should prevent spread because it will prevent your body from producing large quantities of the virus and hence prevent viral shedding.
The remaining factors which still require masks are the non-perfect efficiency (~5% of people will still get it), social factors (related to creating two classes of people; the immune and non-immune) and perhaps some others I forgot.
While I think I agree with you high-level, you and GP may be talking past each other when you use “prevent” when you more precisely mean “dramatically reduce [possibly to the point where you effectively prevent]”.
You're right. I also just found out about research (mentioned somewhere downthread) on differences between antibody expression in different tissue types (some IgA subtypes predominantly found in mucosa while other IgG types being dominantly systemic and/or in the lower respiratory system). The discussion there is on a whole other level of precision and points toward a mechanism which might indeed make it possible for vaccinated people to transmit the disease with some degree so it's not quite as clear cut as I presented it.
Though, intuitively, I'd still bet that vaccination will reduce viral shedding and the total load shedded, thus also reducing transmission.
Even if it's unknown, my advice is still the correct advice, and this is what is recommended by medical professionals. Wear a mask after you got the vaccine.
You cannot say definitively “this is not true”. The advice to wear a mask after vaccination is still the best advice with the data we have, but you made a statement of fact that is currently unknown.
It's been covered well in other comments, so read the whole thread, but basically it's expected that the vaccine would greatly decrease your ability to spread if not completely eliminate it. It's just pending hard data which is a bit complicated to study.
tl;dr per this Nature article, there's different type of antibody responses, intramuscular vaccines are better at inducing the flavor of antibody that works in the lower respiratory tract (which is excellent at attenuating disease severity) but not the kind that works in the upper respiratory tract. Also afaict, sars 2.0 reproduces in the upper respiratory tract, and it's this type of reproduction that allows for disease spread.
i'm not a virologist nor an immunologist but this is my understanding of the situation.
> it is important to note that natural infection induces both mucosal antibody responses (secretory immunoglobulin A (IgA)) and systemic antibody responses (IgG). The upper respiratory tract is thought to be mainly protected by secretory IgA, whereas the lower respiratory tract is thought to be mainly protected by IgG27,28,29. Vaccines that are administered intramuscularly or intradermally induce mainly IgG, and no secretory IgA30. It is therefore possible that most vaccines currently in development induce disease-preventing or disease-attenuating immunity, but not necessarily sterilizing immunity (Fig. 2).
> The lower human respiratory tract is thought to be mostly protected by IgG (IgG1 is most prevalent), the main type of antibody in serum, which is transported into the lung. The upper respiratory tract is thought to be mostly protected by secretory IgA1 (sIgA1). a, Natural infection with respiratory viruses induces both a systemic immune response, dominated by IgG1, as well as a mucosal immune response in the upper respiratory tract that is dominated by sIgA1. This process can lead to sterilizing immunity for many respiratory viruses. b, Intramuscular or intradermal vaccination leads in many cases to a strong induction of serum IgG but not to an induction of mucosal IgA. Although some IgG can also be found on the mucosal surfaces of the upper respiratory tract, the lack of sIgA often leaves an individual vulnerable to infection of the upper respiratory tract. c, Intranasal vaccination can efficiently induce mucosal antibody responses, thereby potentially providing sterilizing immunity in the upper respiratory tract. However, systemic immune responses are often lower after this type of vaccination. Currently, all SARS-CoV-2 vaccine candidates in clinical development are administered intramuscularly, and very few of the more than 180 vaccine candidates in development are designed to induce mucosal immunity. Although mucosal immunity might not be required to protect from severe or even symptomatic disease, it could be required to achieve optimal protection from infection and onward transmission of SARS-CoV-2.
What worries me is that there doesn't seem to be some global coordination in the distribution of the vaccines. It looks more like an individual race, than a synchronized collective effort.
In the scenario where only the old accept to get vaccinated, and the vaccine doesn't reach the required threshold to stomp the virus. The virus become manageable, the economy reopen but the virus run rampant in the asymptotic population slowly mutating over-time until it finds a variant that is resistant to the vaccine by successfully infecting a vaccinated person.
And it just needs for this to happen in a large population cluster where the vaccination doesn't reach the threshold, either because they do not have access to the vaccine yet or because some fraction of the population decide to not get vaccinated, for everyone to get screwed-up again.
Touché ! What is so sad is that it can still be avoided.
But the current situation where we simultaneously have a high number of active case and high number of vaccinated people over a sufficiently long time because of slow vaccination schedule, is a recipe for creating vaccine resistant variants.
As soon as we start vaccinating we are giving the virus opportunities to pressure-select against the vaccine. The more active case we have and the longer it takes the better for the virus.
I'm no epidemiologist, but with the apparition in a short amount of time of 2 variants which affects the spike protein, it seems the current level of active case we are entering a red-zone, where the virus is given too many opportunities to mutate. And we should try to contain it via the current measures (masks, tracking and lock-downs), before sabotaging our best card.
Maybe? The nice thing about mRNA vaccines is that the formula can be adjusted very rapidly (weeks). I feel like if there was a way to tweak the formula fast enough, we could react as fast as the different viral strains mutate. We would need to change the regulatory framework though. Having to do 3 phases of clinical trial involving tens of thousands of participants makes it hard to adapt fast enough.
doesn't the regulatory framework allow such changes though? afaik we aren't doing any phase 3 trials for the annual flu shot, or are we? (genuine question) But if we aren't, couldn't we just expand this to also take into account the Covid-shot?
> we could react as fast as the different viral strains mutate
The number of mutations is proportional to the number of people currently infected. The faster the virus spreads the more variants will be created. The fact that the N501 variant spreads faster seems to imply that the rate of mutations is already in the process of accelerating.
It may make more sense to use evolutionary modeling and analysis of existing SARS-type viruses to create antigens robust to all expected mutations. Here’s one such bit of research:
https://www.biorxiv.org/content/10.1101/2020.11.17.387092v2
Is the risk that’s being assessed by these trials coming from the delivery method of the vaccine? Perhaps maybe there’s a way to get around some of those regulations.
It develops pharmaceutical candidates based on messenger ribonucleic acid (mRNA) for use as individualized cancer immunotherapies, as vaccines against infectious diseases and as protein replacement therapies for rare diseases, and also engineered cell therapy, novel antibodies and small molecule immunomodulators as treatment options for cancer.
It's not just that.
People do develop neutralizing antibodies against HIV.
HIV, like other retroviruses, embedds itself in the cell DNA.
Some cells remain dormant for weeks and then start producing virions.
So the other problem with HIV, even if it didn't attack immune cells, is the hidden virus reservoir, I guess, just like other incurable viruses, like herpes and some hepatitis.
I really don't know enough about immunology to answer that -- but I presume most neutralizing antibodies wane over time.
If you take antiretrovirals you're very unlikely to become infected with HIV, even if you take it after initial exposure (but do your own research on that), but as soon as you stop, you lose that protection -- same with antibodies (not sure how a vaccine would help T-cell immunity if HIV infects T-cells).
While this is indeed a new vaccine modality, it doesn't change the dynamics of vaccinology appreciably. Things that were challenging vaccine targets in the past will likely remain challenging.
Doesn't it change the dynamics insofar as that you have a straightforward path from virus -> its mRNA blueprint, without more specialized and likely costly engineering of e.g. a adenovirus? This should then allow for broader protection against viruses with many strains e.g. a HPV vaccine cocktail that protects against all ~100 known strains vs. just the 9 it currently does.
I'm not suggesting to include new strains on the fly while they are discovered without trials. The same way they had to do trials for Gardasil-9 after already having Gardasil, they could do the same just with a wider cocktail.
In the optimal case you would attempt the 100+ cocktail and don't have any unreasonable side effects from them. Of course if there is a single variant in there that causes side effects you would need a ton of trials to triangulate which one causes them, but there is no guarantee that that is necessary or that you wouldn't run into that variant when you just adding 5 new variants in an iteration.
Even if he is wrong about how it works, because of the potential for unknowns they need to study it in a trial. There is a lot we don't know about biology.
What I haven't seen widely discussed regarding the new variant is whether the higher infectiousness means herd immunity will be achieved later. From my amateur understanding of the SIR model, this should be the case.
So ultimately we may not achieve herd immunity except with mandatory vaccination campaigns.
There is clearly something that prevents certain people (particularly kids) from contracting COVID to the point where they will not test PCR positive even if they are heavily exposed and have not had it before.
I know several families in my town who have gotten COVID. All of these families had 2 or more kids and in 3 of the families there was at least one kid who never had any symptoms and never tested positive despite being PCR tested repeatedly.
It’s theorized that there is some cross-immunity that some people have from other coronaviruses.
Coronavirus is a generic term for a type of virus.
For example, a few of the more common strains of the common cold, representing perhaps 15% of cases, are coronavirus - but they have no real relation to _the_ coronavirus, as term is typically used.
It depends what you mean by real relation. Both OC43 and HKU1 are betacoronaviruses, in the same genera as SARS-CoV-2. So they're genetically very similar, but there's no reliable evidence of significant cross immunity.
I know some of you are following this closely and I have some questions I haven't seen any proper answer. I am hoping one of you can shine some light.
How long will the mod-RNA express the spike proteins? (where is the actual 'protein expression'/time plot?)
The poly(A) tail isn't just A (which would give a mechanic answer to my first question?), there is also a 10-nucleotide linker (GCAΨAΨGACΨ). I wonder if this could be there to trigger some sort of self-amplification. Can someone point me to the relevant paper?
Because mRNA tech for rapid vaccine development wasn't available back then and it didn't spread so far that there was political pressure for expedited trials. Now it is eradicated anyway.
The is/was several SARS vaccines. They never got to phase 3 trials, because of various problems. We learned enough from them to skip all the issues this time around.
How effective is it to use one of those molecular simulation tools to quickly calculate if the antigens created still have high affinity to bind to the mutated spike?
The problem is that we're turning this into a cat and mouse - Pfizer has nowhere near the capacity to ramp up production to make a positive impact after all.
If we enter a cycle of new variants every 9-6 months that require new vacines, simply because the volume of people infect allows the virus to have enough diversity, then it's pointless.
It's basically a "weird flex" from Pfizer, because what they should say is: even though we can make a new vaccine easily, we will have nowhere near the production capacity to make a difference, so global governments need to get their shit together.
Manufacturing capacity is going to be a big constraint this year, but surely whatever factory was going to make the old variant, could equally well make some new variant of the vaccine.
Longer-term, if we need a new vaccine every 9 months, that doesn't sound like a huge manufacturing problem. We manufacture many high-tech things on a scale of 1 per person per year, like the flu vaccine. The difficulty is ramping up fast (especially when you think that demand may only last a year).
It's the whole chain, manufacturing is just a portion of it - the logistics required for this vacine, and the volume of people that needs to be vaccinated.
Pfizer can develop more capacity if they see a need. Right now it isn't looking useful, as several other competitors are expected to be approved in the near future before they can bring more production online. If they need to develop a new vaccine every few months, the speed they can make new variations would make more investment in manufacturing worth it.
>>> appears effective
I'm not knocking the vaccine, but that's a pretty low scientific standard.
The public is so polarized that we have crazy conspiracy theories on one side, and complete acceptance with very little questioning on the other side.
A typical drug takes about 5 years to develop and another 5-7 for clinical trials, and for good reasons. It takes time to discover side effects. This vaccine has been developed in less than a year from virus discovery to production.
I really hope this vaccine works, but I can understand the skepticism.
This is incorrect. Vaccines take forever to develop for economic reasons. Big studies are very expensive, so companies are typically quite hesitant to move to the next step. Vaccine side effects are usually quite rare, so you wouldn't see them in a Phase-3 trial, even if you waited for decades. This is why any drug is studied after approval in Phase-4 trials. Furthermore, vaccines side effects have historically pretty much always shown up at most weeks after the vaccination.
Why should it be not? It will be effective as long as the core protein against which the immune system response is to be triggered will remain the same.
There is certainly something going on in the UK and Ireland, but it's not a randomized controlled study designed to measure the infectiousness of the variants that have recently been sampled there.
(because it's exponential, higher infectiousness can be quite a lot worse than higher lethality)
There is. In the UK you are seeing a huge spike in infections at the same time the percentage of coronaviruses attributed to the new variant sky rocket.
Look here for how one of the lines is not like the others. (UK)
It should be noted that increased infectiousness will inherently result in a larger number of deaths, even if it is not "deadlier". i.e. the new strain may still only be fatal in 0.5% of cases, but if it infects more people that's more rolls of the dice. The original strain was only projected to infect 60-70% of the population (if left unchecked). A new strain being 70% more infectious drastically changes that figure.
Not to mention a similar uptick in serious cases and even just more people presenting to the hospital. Imagine the current situation, where some cities are already at 0% capacity, but 70% worse...
Just something worth noting when we say that a new strain is _just_ more infectious.
Yep, but at the same time if they would have said that it is "more infectious and more deadly" - that would have even more incorrect (without clarification), given that those terms usually refer to specific properties.
Actually it isn’t wrong. A 70% increase in an exponential gain leads to many multiples more cases.
You could halve the death rate in that scenario and still have 10x the number of deaths or more.
Run two exponential series: one at 1.1x, one at 1.7x. Start at 1,000 cases each. Death rate 1% for the first, 0.5% for the second. Assume doubling in a week. Check new cases and thus new deaths after eight weeks.
2143 new cases on week eight fir the second one, 21.4 deaths.
110,199 new cases on week eight for second one, resulting in 550.5 deaths.
20x worse. And unfortunately the new strain doesn’t seem to be less deadly, so it would be 40x worse if death rate the same.
You are wrong on principle because you stopped thinking after you calculated the death rate after week eight. The virus doesn't stop spreading in either of the hypothetical cases and the population is a finite number. Keep calculating!
Also, your numbers are arbitrarily picked. Why don't you pick 1.8x and 1% vs. 1.9x and 0.999%?
Because 1.1x is about the r pre-existing restrictions had most western societies at. And it’s estimated the new variant is 70% more transmissible.
>You are wrong on principle because you stopped thinking after you calculated the death rate after week eight. The virus doesn't stop spreading in either of the hypothetical cases and the population is a finite number. Keep calculating!
This only applies if the plan was to let literally everyone get infected. That wasn’t the plan. We have vaccines now. It should be possible to end things by the end of summer, so excess deaths now are needless deaths.
Also you’re ignoring speed. 200,000 hospitalizations in a week is much much worse than 200,000 in a year. Get too many people needing to be hospitalized at once and the death rate goes up because you can’t treat them as well. You also get more deaths from other conditions as hospitals can no longer serve cancer patients, heart attack victims past a certain point etc.
You keep introducing more variables and more arbitrary numbers, we won't get to agree on anything this way.
It's well known that harmless viruses exist, they infect a lot of people and kill nobody (or almost nobody). Claiming that more infectious = generally more lethal is just not based on facts. If Covid-19 mutates into a mostly harmless variant, we will easily treat the few more severe infections and nobody will die.
> You keep introducing more variables and more arbitrary numbers
These variables are the ones that are relevant to deaths and have been talked about since the beginning of the pandemic: hospital overwhelm, total percent of populace infected, etc
To refuse to deal with the complexities of the situation doesn’t make them go away. I didn’t introduce any factors apart from the common ones.
> It's well known that harmless viruses exist, they infect a lot of people and kill nobody (or almost nobody).
We’re not talking about those viruses though. Most viruses that we don’t have a vaccine for are either orders of magnitude less lethal or substantially less contagious.
> Claiming that more infectious = generally more lethal is just not based on facts.
I didn’t say that. I said that at the level of lethality coronavirus is at, an increase in contagiousness is worse than an increase in lethality. Very different claim.
> If Covid-19 mutates into a mostly harmless variant, we will easily treat the few more severe infections and nobody will die.
This would be true if it mutated into something maybe 100x less contagious. An entirely theoretical possibility. That’s how much more lethal covid is compared to stuff like the cold.
It's been rapidly becoming the dominant variant in places with various different kinds of measures so I think it's for sure more infectious at this point.
So incessant, and seemingly ineffective, lockdowns have succeeded - in selecting for a variant of COVID which is resistant to lockdown? What biological or physical mechanism could allow it to spread more than the original?
On one hand, it may be plausible that taking any measure that makes it harder to spread... favors a variant that can spread more easily.
On the other hand, spreading more easily means higher reproductive fitness under any circumstance. And not taking measures to reduce spread probably just means more infections faster, which is more opportunity for reproduction and mutation, which means you probably get higher fitness variations sooner.
Also I'm trying to think of anywhere in US/UK society for which "incessant lockdown" could possibly be an accurate description of policy much less behavior.
Imperial study was in the context of a tiered UK system that keeps schools, so increased infection from young people is my personal and ill-informed hypothesis of how the new variant achieved 50-70% increased r0 under restrictions.
Just a reminder that greater infectiousness is worse than greater lethality.
Say you have two variants, variant S-spreader and variant L-lethal.
S kills 1 in 100 people and has a doubling time of 3.5 days
L kills 2 in 100 people and has a doubling time of a week.
First week L kills twice as many people of S.
Week 2 they kill the same number of people.
Week 3 S kills twice as many people as L
Week 4 S kills 4x as many people as L.
This is plain wrong. You have 2 variables there and can't claim that one has greater effect based on 2 examples. It can be refuted by a suitably chosen 3rd example, e.g. N-nonlethal kills 1 in 10000000000000 people and has a doubling time of 1 day.
The vaccine works on the new variants. The variant spreads faster than previous ones, but in the end the rules don't change: Wear a mask, wash your hands, don't go inside with people if possible.
People were sharing on a Facebook and tweeting that the new strain was being spread through touching surfaces and farts and that masks no longer work.
Big Tech is poison and many thousands would still be alive today if they had never logged on. These companies are no longer defensible.
The problem is that, because the variant spreads faster than previous ones, rules which were sufficient to keep previous ones in check will likely be insufficient to keep the new one in check. We'll have to get stricter about the rules, get vaccine rollout accelerated quite a bit, or find ways to handle a lot more disease than currently exists. I have no doubt some people shared weird falsehoods about it, but there's still a true reason for concern.
Speaking from California, the only change we could make is convincing law enforcement to enforce the rules (they won't) and changing the bizarre vaccine restrictions that are leaving 75 percent of our doses in a freezer while thousands who are offered it say no thanks.
A massive percentage of the public has decided to give up on safety protocols and if Thanksgiving and Christmas didn't change any minds, why would this?
What good did terrorizing the people who are already following the rules with this variant panic do? "THE VACCINE MIGHT NOT WORK NOW!" only scares people who want the vaccine. The media frenzy around the variant did absolutely no good.
What's bizarre about the vaccine restrictions? The publicized plans I'm aware of start with healthcare workers and long-term care residents, which is pretty much what I expected. I've heard there are about 3 million of those people and 1 million doses, so even if over half of those people for some reason are refusing doses, there's no reasons to expect that we're through that crowd yet.
I've got several acquaintances who work in both areas and what I'm hearing that there are challenges: not ones that have to do with "rules", but actual supply and logistics. Still, among these are people who've received their first dose.
There's been a serious problem im CA with Healthcare workers rejecting vaccines which are then either discarded or put away in a freezer. Only 25 percent of the supply has been used, including the ones reserved for dose 2.
What you're saying is probably true. But I don't think the media should refrain from reporting true, relevant information just because they don't think it will do any good if it's known.
Oh, of course news should be reported. But a week straight of panic mongering headlines? That does people a disservice and spreads fear for $. Big Tech and corporate media have a profit incentive in spreading terror.
What worries me is the chance that we will see another super virus in a few years except one country already has vaccines developed on day one and will not share the information on them.
I feel like in this economically connected world, that would be a sort of global politics suicide. It would be one of the few acts that would likely galvanize... everyone. The leaders of those nations would be pariahs in a way that even a nation like N. Korea is not.
For the nation's without a vaccine, the leaders there likely would be quite motivated to act and enjoy a great deal of support at home.
Remember China and the USA were in a full bore trade war and despite some mud flinging and half-truths,essentially the global health system was kept informed.
The genome was shared. At least four competitors in global economic terms (China, Russia, the EU and the USA) all developed vaccines.
This is not like pre-hydrogen bomb information hoarding. The techniques behind mRNA are taught worldwide. Most medicines come from India, which was a leading non-aligned economy for years and years.
In general sharing vaccine information with your enemy is considered a good thing by generals. No good army wants to get involved in biological warfare at this time as it is too risky as to turning against you.
The above does leave room for bad armies. Some tiny insignificant nation might do this. China isn't insignificant, and not stupid. Even in an all out war they would still share virus and vaccine information with their enemies as there is nothing to lose and goodwill to gain.
[1]: https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1
[2]: https://www.biorxiv.org/content/10.1101/2020.12.31.425021v1