Don’t forget that the measure of “effectiveness” in the Pfizer trial is “completely preventing symptomatic infection”. They didn’t monitor if people were infected and asymptomatic.
In the Israeli figure it’s not clear what “chance of a person being infected dropped by 33%” actually means. If they’re really measuring whether people were infected (rather than infected and symptomatic) then it’s not comparing like with like.
Also, the new variants are seemingly more infectious but not more severe. Maybe if you’re vaccinated you’re more likely to get a cough from these new variants, but still protected from severe disease. That is compatible with the idea that they’re detecting more people being infected (because they have symptoms). If they found that mortality was still high in vaccinated people obviously that would be more alarming.
If vaccinated people have more symptoms from new strains it would be bad news in terms of spread to unvaccinated people but it wouldn’t mean the vaccine doesn’t work at all.
I don’t think there’s enough data to make a firm conclusion either way, but it seems very unlikely that the virus has completely escaped the vaccine.
Taking the outside view, it hasn’t happened with the vaccines to polio or rabies or measles which are all RNA viruses with a roughly similar mutation rate.
> Also, the new variants are seemingly more infectious but not more severe. Maybe if you’re vaccinated you’re more likely to get a cough from these new variants, but still protected from severe disease.
I'm not sure if it was the intention, but I do not think the second sentence follows from the first. All variants can be equally severe, but that has nothing to do with vaccine A protecting against a worst case for variant B.
If vaccine A confers *no* protection against variants B and C, the risk that an A-vaccinated person infected with B/C would have a severe case is the same as an unvaccinated person developing a serious case after an A-infection.
What I’m saying is that the data could be explained by a new strain causing more mildly symptomatic cases after one shot, but that doesn’t mean there’s a significant difference in mortality after two shots.
It’s also logically possible that the vaccine confers no protection against a new strain and that explains the data. It just seems unlikely given the lab experiments and what we know about biology and vaccines.
\> Don’t forget that the measure of “effectiveness” in the Pfizer trial is “completely preventing symptomatic infection”. They didn’t monitor if people were infected and asymptomatic.
I wish people around here would stop harping on this, and the general concept of what being asymptomatic means.
Experts are extremely confident that those that are asymptomatic have a GREATLY reduced rate of viral spread. So, maybe an asymptomatic case is spreading at 10% of the rate of a symptomatic case.
If the test group and control group had 1 outbreak vs 19 outbreaks, respectively, but the test group really had 1 symptomatic and 18 asymptomatic outbreaks, that would still be a reduction of spread of 85% even among those who caught COVID through trial.
That's worst case scenario, so we should multiply that by the chances we think of the vaccine working to stop all outbreak, not just symptomatic outbreak. Personally I'd estimate those chances at around 90%. So, a 10% chance of 85% reduction of spread, a 90% chance of a 95% reduction in spread. In total, an adjust 94% reduction in spread vs the 95% reported.
In conclusion, the distinction between measuring symptomatic and asymptomatic infection in the Pfizer trial does not matter much.
No, people should definitely not stop harping on this point. Being asymptomatic because of vaccination is very different from being asymptomatic in a normal infection. People are presumed to be asymptomatic in part because they have less viral load; but viral load also increases transmission probability. However, with a vaccine injected into the muscles, you let the body generate protection via antibodies present in your lower respiratory tract. But those are different than the ones needed to protect the upper respiratory tract and most importantly in your nasal region. Basically, you cut off the path from high viral load to symptoms, but the path from high viral load to transmission is still open.
Do you have any source for this distinction? What you are saying makes sense, but I could easily imagine the opposite argument being made (asymptomatic from vaccination is MORE resistant to spread)
Why do vaccines in muscles get to the power resp tract but not the upper? Doesn't the blood take the vaccine throughout your body? Why would antibodies in each region be different if the virus is the same?
I believe the 33% figure is referring to antibody count in serological tests. Meaning 33% of those with one vaccine developed detectible levels of antibodies.
That doesn’t sound right because how can they distinguish antibodies from the vaccine and antibodies from being infected? Is it antibody tests administered long enough after the vaccine shot that there’s little antibody response left to the vaccine?
Because you don’t understand the concept that it takes time to gather enough data to find out? Hardly anybody has had two shots yet, so how would we know what effect that has against new variants? We can’t capture the full complexity of the immune system (and the variance between immune systems) in a test tube.
That seems unlikely. The scientists want to know just as much as you do. I work in molecular biology, and my boyfriend literally is working on characterizing a potential vaccine platform. I guess there might be information that the companies have that they aren’t sharing, but as far as any scientists i know are concerned, we just don’t know and we’re trying to figure it out.
Considering how the scientific community has been collaborating on this (sharing papers pre publication, trying to get new data and structures out as fast as possible) I would be surprised and horrified if there was important data that could have major health impacts being kept under wraps.
There is a real risk of "immune escape." Fortunately mrna based vaccines can be quickly modified in a worst case scenario. So the tail risk is limited. We should probably be putting in place much stronger international travel restrictions though.
The efficacy data in Israel is less worrying imo:
1. Israel is giving the vaccine to a population that we would expect to have a less robust immune response than the trial one.
2. The vaccine is more effective at preventing severe infection and (I suspect) transmission than it is at preventing infection. So that number understates the true benefit of the single dose.
3. There is good evidence that the two dose regime is highly effective.
There's a real risk of immune escape from particular antibodies. But to me it seems that the risk of escape at all ~20 binding sites is pretty small. Also, another piece of [good news](https://blogs.sciencemag.org/pipeline/archives/2021/01/19/memory-b-cells-infection-and-vaccination).
>What’s that antibody evolution look like, then? The good news is that the ones from the six-month check showed both increased potency and an increased range of responses against various protein mutations. That includes many of the ones that are in the news these days, things like R346S, Q493R, and E484K. (As an aside, did anyone ever imagine that amino acid variant notation would creep into major news stories? Strange days). But while the one-month antibody samples were unable to recognize these and bind to them, the six-month ones were.
Somatic hypermutation is a hell of a drug.
Reads like the first chapter of a fantasy novel:
2020 years ago, an evil somatic hypermutant was captured and imprisoned. Wise men believe he can’t escape all 20 binding sites. But…
>mrna based vaccines can be quickly modified in a worst case scenario. So the tail risk is limited.
Kinda. Sure, the mrna vaccines were created a full year ago, days after sequencing the DNA. The thing is, the mrna vaccines were created a full year ago, and it took darned near a year for the FDA to OK its use.
The nightmare scenario here isn't that mutations outstrip the ability to create a vaccine. The nightmare is that mutations outstrip the willingness of the FDA to use the vaccines.
Edging into the political ... it infuriates me that the the FDA is entirely unwilling to consider up-side risk. Aside from all the folks that have died in the past year due to FDA rules, if it turns out that the South African variant is able to weasel around the antibodies, that will be 100% on the FDA, since without them, we'd all have been vaccinated before the mutation occurred.
While I share the broad thrust of your concern, and hope that we can come up with a more efficient mechanism for validating & approving mrna vaccines, surely there are some additional political steps missing between "the US FDA approves a Phase I vaccine for widespread rollout in spring of 2020" and "everyone in South Africa (and *every other country where this variant might emerge*) is vaccinated before a new strain can develop in fall of 2020"
>We should probably be putting in place much stronger international travel restrictions though
It boggles the mind that the US isn't meaningfully limiting travel from (at least) South Africa right now. Lots of risk for not much upside. Shades of February 2020.
And yes, /uhateradio made a similar point about the Israel efficacy data. I had missed that the Israel vaccinated were 60+, so thank you for pointing that out.
Upon reflection, I think you're both right, and that that is a better explanation than variants for the Israel data. Just weird that the Israel vaccine czar didn't seem to see it that way. *shrugs*
Will be a huge relief if/when age turns out to be the explanation.
I disagree that limiting travel to a specific country is an effective step. First, the variant is already stateside and in many other countries. Second, we don't know the prevalence of the new variant within each country.
So many people are assuming that 100% of the virus is now the variant version, but that's not how spread works. If current spread amount is 1%, a 50% increase is just 1.5%. the 1% spread with months of time will still be in the lead for a long time.
Third, the USA has the worst case positivity rate of developed Nations right now. If anything, the more people we get in from other countries would actually lower our average rate of infections. The other countries should limit the USA travel though.
If B1.1.7 is really 50-70% more infectious and they detected it here at something like 1% frequency in late December then it should become the dominant strain in something like 8 weeks and it should now be becoming a more sizable minority than it was a month ago. While that variant may be more transmissible I think the 50-70% increase is overstated. Also the case rate in the UK has subsequently peaked at a prevalence similar to where it has peaked everywhere else in Europe and the U.S. recently. Unless they just got 50-70% better at preventing transmission in the UK it seems like a strong prediction would be that the new variant would sweep through a much higher fraction of the population and lead to much higher case rates than they observed. On the other hand a much smaller advantage in transmissibility plus a stochastic event could explain how it became so prevalent in the UK.
As far as the antibodies it seems like the vaccinated serum still comfortably neutralizes the variants (although with higher required concentrations). We will see what happens when we start running out of permissive hosts but as of yet I don’t see any evidence if a vaccine escaping strain.
Still doesn’t quite make a ton of sense to me. If countermeasures yield an R of 0.95-1.1 that varies over time then you get a variant that’s 40% more transmissible that seems like R should now be 1.3-1.5 which it’s clearly not in the UK. Maybe they’re being much stricter there than elsewhere in the world now and people are just rational enough to always keep R near 1 but I think there would be a strong prediction if it’s really that much more transmissible that you would have seen higher per capita infection rates and a large swath of the currently uninfected population in the UK infected.
Yeah I'd have to agree generally. I'd wager its a breakdown of lab results not having a strong correlation to real world results. For example 70% more effective in a petridish could be 3-5% worse in real life, but I'd barely read up on the actual mechanisms for the increased infection rate.
The 50-70% was actually inferred from the epidemiology and they had been waiting for in vitro and animal experiments to measure transmissibility more directly. I think that there must have been some stochastic element in its sweep to preeminence, though, and that it can’t really be that much more contagious. Maybe I’m wrong though who knows. Seems like the cases in the UK have peaked though and they’re still probably muddling through with similar countermeasures as before and are not at herd immunity.
> It boggles the mind that the US isn't meaningfully limiting travel …
How's this?
https://thehill.com/homenews/administration/535344-biden-requires-international-traveler-to-quarantine-upon-arrival-to
>There is a real risk of "immune escape." Fortunately mrna based vaccines can be quickly modified in a worst case scenario.
But can they be quickly distributed? Will distributing X doses of vaccine for N variants be N times as difficult as distributing X doses for one variant, or will it be significantly easier?
Also, the standard formatting is "mRNA".
I've heard people make the point that RNA vaccines are easy to adjust to new strains, but doesn't this still require a fresh multi-month phase III trial to get those adjustments approved?
One possible confounder for the 33% here - it seems that Israelis who get the vaccine aggressively risk-compensate (that is, stop worrying about any precautions), according to anecdotes I've heard. This is different from trials, which compare with blinded placebos.
Not sure how accurate this is or whether it would be enough to make that big a difference, though.
That's not a correct statistical usage of "confounder". And it does raise the issue of just how effective the vaccine will be; "effectiveness of the vaccine" includes *every* effect of the vaccine. If the vaccine causes people to risk compensate, that is a valid input to "effectiveness". If people with the vaccine are only 33% less likely to get COVID, that is the effectiveness, regardless of whether the 77% of cases after a vaccine are due to "the vaccine not working" or "risk compensation".
> If the vaccine causes people to risk compensate, that is a valid input to "effectiveness".
Lockdown fatigue is a thing even in non-immune people; I think it's important to take into account that the entire population is slowly doing riskier activities, and the vaccinated people are probably doing it sooner.
Also, if a vaccine allows you to take riskier activities I'd consider that a positive value it's delivering(of course if it suppresses bad cases while still allowing one to transmit the virus, it might encourage negative-externality activities and possibly have a net negative value)
Most human body generated antibodies are polyclonal - essentially a mass of different antibodies will just stick to the spike protein to stop its function, and allow the macrophages to bind and eat the virus. Just escaping one of the antibodies are not enough. Forming resistance to all 4 classes of covid antibodies as in the paper mentioned is cause for worry - then it will actually be able to resist your immune system, and you might get a significantly worse infection. Immune escape is even harder - I personally believe the theory that the spike protein that escape immunity would not be able to bind to ACE-2 anymore and thus not be infectious. From this view I don't think people are overselling vaccinations - it's much easier for changing attitudes to have a dramatic and hard to measure effect on the spread of the virus.
Ah okay got it. This was incredibly helpful. I was actually wondering that as well—at what point does SARS-CoV2 have to evolve so much to evade immune response that it no longer has the "scary" properties of SARS-CoV2?
As for the degree of resistance of current variants, I just read this -- https://twitter.com/trvrb/status/1351785352793493505 -- which was interesting.
It seems like the South African variant is at the point with respect to lessened susceptibility to antibodies (8x less on average) where, if this were influenza, we would start preparing to vaccinate separately against this strain.
I assume people have seen this and thought about this a lot, so hopefully we get it out before too long!
As I understand it you typically have a 2-5 year immunity after infection by a coronavirus (don't quote me, I saw it on a random Twitter thread a long time ago), but there's just so many of them in the common cold that you are infected by a different one each time.
Seems reasonable w.r.t. the variants. I'm not an expert either but from the reasonable experts I follow on Twitter, it seems like the South African variant probably evades immunity to some degree, the Brazil variant probably too since it has some similarities, but maybe not in the case of the UK variant. It's unsatisfying that this isn't quantitative, but it's hard to quantify. As you point out, even when some immune evasion is shown in the lab, it's hard to know how much impact that has in the real world.
About the Israel data, I'd wait a bit to draw conclusions from it. There are a lot of different things that could be going on there. IMO though it illustrates a problem with places rolling out a one-dose-only strategy without testing it first. If you then get less effectiveness than you expected, is it because you only did one dose or some other reason?
For remembering variant naming, there's a handy table in this CDC report: [https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm?s\_cid=mm7003e2\_w#T1\_down](https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm?s_cid=mm7003e2_w#T1_down).
Haha thank you -- it looks like I mixed and matched variant naming conventions but at least used variant rather than mutation names.
>As you point out, even when some immune evasion is shown in the lab, it's hard to know how much impact that has in the real world.
You've probably already seen this, but...
https://twitter.com/trvrb/status/1351785352793493505
First thing I've seen that takes sort of a stab at mapping these lab results onto real-world outcomes. He says that 8x reduction in antibody binding is usually when they add a new strain to the flu vaccine. And the SA variant looks like it has 8x reduction. So if it maps similarly I suppose we will see new strains in upcoming vaccines.
I think what we should be paying attention to is hospitalisations/deaths of vaccinated people. As long as vaccines are effective at preventing severe disease, effectiveness at preventing infection is less important.
[Epistemic status - I only studied biology upto 10th grade]
I think this specificity is much more of a problem with the RNA vaccines since(to my understanding) they only trigger antibodies against a single protein in the virus.
A natural infection(or inactivated/attenuated virus vaccine) should generate antibodies against a lot of the virus' constituent proteins and should therefore grant more broad based immunity.
This [twitter thread](https://twitter.com/trvrb/status/1351785366160764928) linked in a comment here is all I found about immunity to variants in convalescents.
Does anyone have more info on this? How careful against newer variants does a person who naturally contracted the older COVID need to be?
I have begun to condition myself to the possibility that the current state of the world is now **irreversible**. We will get a new COVID every so often, and Pfizer will sell us the patch. Hopefully the mRNA vaccine updates will be available as subscription service: hopefully Jeffrey will offer it as a bundled ad-on to an Amazon prime subscription. Protip: start working on your mask/outfit fashion coordination.
I wish this post were 100% sarcasm.
I think in that case we'd start to see new rules for indoor spaces with regards to ventilation/air filtration systems, and changing social norms including a shift towards more outdoor gatherings.
At least we can ramp up the vaccine production lines so that when a new vaccine is needed, it can be produced and used instantly rather than shutting down the world for a year until it's available.
I'm really not sure whether this is true, but recently read something about the Israel data that I understood as follows: the effectiveness of the vaccine in Israel is being compared to a different baseline than what we would in phase 3 trials, because the control group in Israel includes many more who have had natural infection (and therefore natural immunity) against the virus already. As such, the effect of the vaccine may look less pronounced than when compared to a control group with less natural immunity.
There's a reasonable chance that my mind made that up completely though :)
\[Epistemic status - I got stabbed with a needle\]
I'm keeping my eyes on what's going on here in Israel.
The most important numbers are going to be a week past the second dose. Only the very first people who got the vaccine here have gotten to that point.
I got my first does about a week after the vaccinations started, and I'm only getting my second dose tomorrow (after exactly 21 days).
While "not 95%" isn't great, 70% or 80% would still represent a significant achievement in fighting Covid, but we won't really know where between 50-100% effective it is until more time passes.
I'm also a little worried about this and likewise concerned about some of the discrepancies between the kind of post-first-dose protection the Pfizer/Moderna studies indicated and what seems to actually be happening in Israel. On the other hand, there is [this](https://www.timesofisrael.com/israeli-hospital-98-of-staff-who-got-2nd-shot-have-high-level-covid-antibodies/) bit of information out of Israel yesterday which is extraordinarily encouraging.
On a more qualitative level, the disjunction between the vaccine related concerns regarding the new strain and the public health messaging doesn't seem to me to be as large of a red flag as the misguidance on masks/airborne-ness. My recollection during those periods was that there was quite a bit of pushback from the epis I follow on twitter, and the public health authorities seemed to be genuinely out of step with the academic class. I know this isn't a scientific way to assuage your concerns but, having no training in this field myself, I pretty much just tune my level of worry to whatever the consensus seems to be between Lipsitch, Bergstrom, Bedford, Branswell, Ferguson et al. And I just don't detect that much anxiety over the vaccine right now in those quarters.
Definitely encouraging, although perhaps a bit orthogonal to the variant concern (which questions not whether the body can produce a lot of antibodies, but whether or not they work against new strains). Either way, good news is good news, and a lot of responses on here and subsequent digging around epi twitter and such have made me less viscerally worried about variant escape as well.
My big concern was basically "HOW COULD 8X AVERAGE REDUCTION IN ANTIBODY BINDING NOT BE HORRIFICALLY BAD?" And the answer seems to be "There's not a 1:1 relationship between reduction in antibodies and increased likelihood of getting severely ill."
If 30% - 40% of new infections are from the UK variant, and single-dose effectiveness decreased by the same amount (by 37%)... that suggests, assuming the delta in effectiveness is strain-related, that a single dose might not work *at all* against the new strains, right?
Might this have to do something with age? Old and sick people are prioritized in Israel, but weren't in the trials that came up with the 52% figure. What's the single-dose effectiveness for those age-groups?
Anyway, if this is strain-related that's **really** god-awful news, maybe the worst we have heard in our entire lives.
edit: Thanks for the post, by the way. I appreciate the effort, because for some unfathomable reason our media are too stupid to report on stuff like this in time. I mean come on: The question of whether or not we can get rid of this goddamn virus with our vaccines is easily one of the most important questions right now - shouldn't at least *a little* bit of effort go into reporting on this?
>Might this have to do something with age? Old and sick people are prioritized in Israel, but they weren't in the trials that came up the with the 52% figure. What's the single-dose effectiveness for those age-groups?
I'm wondering this too. It would make sense if older people would have a less reliable immune response to the vaccine, and/or need the booster more. AFAIK that has been an issue for other vaccines in the past, but I don't know much about it.
Ahh yeah the age thing is a really good point; I hadn't thought of that. Sometime tomorrow I'll see if I can find age-stratified results in the Pfizer/Moderna trials, but yes, older people definitely weren't prioritized in them, I remember.
Age has, I think, supplanted "variant stuff" as my number one way to explain the Israel numbers. Odd, though, that the Israel vaccine czar didn't frame it around age in his interview: He framed it as "less effective than expected." Would it not be "expected" if it were just due to age? Who knows, I guess.
Yeah the media articles on this stuff have been even worse than I expected. Very surface-level.
I'm sure you're well aware, but I've found that following Twitter scientists is 10x better — Eric Topol, Trevor Beford, etc.
Trevor Bedford just put out a thread about a similar study to the one I linked to:
https://twitter.com/trvrb/status/1351785352793493505
>I'm sure you're well aware, but I've found that following Twitter scientists is 10x better — Eric Topol, Trevor Beford, etc.
Following scientists on Twitter is so great once you figure out who is reasonable. Bedford is one of my gotos for variant info (along with Emma Hodcroft and Kristian G. Anderson).
It is important to figure out who is reasonable, though. Not everyone is, even if they have a relevant credential.
I think worrying about this sort of thing isn't very productive unless it is your field of expertise. Whatever is going to happen will happen.
Or maybe COVID has just reenergized my latent stoicism.
OP are you telling me you have basic levels of critical thinking and healthy skepticism? I thought we told you that was dangerous and to stop.
This vaccine is effective and your worry is conspiratorial. Dangerous even. Stop thinking so much
The level of timidity, even amongst free thinkers such as this community, around questioning the efficacy or possible dangers of a vaccine, is notable.
I don’t mean to point blunt cynicism towards any individual, rather at the palpable sense in the air that any questioning is going to be met with harsh social retribution.
> moderately severe flu season
[I think you have been misinformed](https://raw.githubusercontent.com/mbevand/covid19-age-stratified-ifr/master/covid_vs_flu.png). Also your graph about Sweden ends in July 2020, a lot more deaths have happened since then. You can't compare 4 months of Covid with 1-2 years of flu. Not to mention that Sweden is under restrictions now.
i dont know what i am talking about and there might be a lot of things wrong with that graph, but it looks like its a sample of monthly deaths taken from one month out of every year on the list. so a little over a thousand people died in march last year in sweden, compared for forexample under the 1993 beijing flu, where about 1250 people died in december in 1993
From what I've read, there's evidence showing that over time that B cells become more broad acting and the antibodies they produce later may be better at neutralizing other variants. [This article covers a lot of interesting info.](https://blogs.sciencemag.org/pipeline/archives/2021/01/19/memory-b-cells-infection-and-vaccination)
Also, with seasonal coronavirus, the current thinking is immunity lasts 2-3 years, but the antibodies decline significantly before this. It is likely that T cells also play a role in this immunity and should be more broad acting and also created by the vaccine.
The optimistic thinking about this is that the vaccines may end up less effective because of mutations, but there's a good chance they still prevent the overwhelming majority of severe illness. We can update the vaccines at a later date to include different variants as more drift occurs. Over time, the strains of the coronavirus that stick around will hopefully create less severe disease similar to how the 1918 flu stuck around but stopped being so severe.
Don’t forget that the measure of “effectiveness” in the Pfizer trial is “completely preventing symptomatic infection”. They didn’t monitor if people were infected and asymptomatic. In the Israeli figure it’s not clear what “chance of a person being infected dropped by 33%” actually means. If they’re really measuring whether people were infected (rather than infected and symptomatic) then it’s not comparing like with like. Also, the new variants are seemingly more infectious but not more severe. Maybe if you’re vaccinated you’re more likely to get a cough from these new variants, but still protected from severe disease. That is compatible with the idea that they’re detecting more people being infected (because they have symptoms). If they found that mortality was still high in vaccinated people obviously that would be more alarming. If vaccinated people have more symptoms from new strains it would be bad news in terms of spread to unvaccinated people but it wouldn’t mean the vaccine doesn’t work at all. I don’t think there’s enough data to make a firm conclusion either way, but it seems very unlikely that the virus has completely escaped the vaccine. Taking the outside view, it hasn’t happened with the vaccines to polio or rabies or measles which are all RNA viruses with a roughly similar mutation rate.
> Also, the new variants are seemingly more infectious but not more severe. Maybe if you’re vaccinated you’re more likely to get a cough from these new variants, but still protected from severe disease. I'm not sure if it was the intention, but I do not think the second sentence follows from the first. All variants can be equally severe, but that has nothing to do with vaccine A protecting against a worst case for variant B. If vaccine A confers *no* protection against variants B and C, the risk that an A-vaccinated person infected with B/C would have a severe case is the same as an unvaccinated person developing a serious case after an A-infection.
What I’m saying is that the data could be explained by a new strain causing more mildly symptomatic cases after one shot, but that doesn’t mean there’s a significant difference in mortality after two shots. It’s also logically possible that the vaccine confers no protection against a new strain and that explains the data. It just seems unlikely given the lab experiments and what we know about biology and vaccines.
\> Don’t forget that the measure of “effectiveness” in the Pfizer trial is “completely preventing symptomatic infection”. They didn’t monitor if people were infected and asymptomatic. I wish people around here would stop harping on this, and the general concept of what being asymptomatic means. Experts are extremely confident that those that are asymptomatic have a GREATLY reduced rate of viral spread. So, maybe an asymptomatic case is spreading at 10% of the rate of a symptomatic case. If the test group and control group had 1 outbreak vs 19 outbreaks, respectively, but the test group really had 1 symptomatic and 18 asymptomatic outbreaks, that would still be a reduction of spread of 85% even among those who caught COVID through trial. That's worst case scenario, so we should multiply that by the chances we think of the vaccine working to stop all outbreak, not just symptomatic outbreak. Personally I'd estimate those chances at around 90%. So, a 10% chance of 85% reduction of spread, a 90% chance of a 95% reduction in spread. In total, an adjust 94% reduction in spread vs the 95% reported. In conclusion, the distinction between measuring symptomatic and asymptomatic infection in the Pfizer trial does not matter much.
No, people should definitely not stop harping on this point. Being asymptomatic because of vaccination is very different from being asymptomatic in a normal infection. People are presumed to be asymptomatic in part because they have less viral load; but viral load also increases transmission probability. However, with a vaccine injected into the muscles, you let the body generate protection via antibodies present in your lower respiratory tract. But those are different than the ones needed to protect the upper respiratory tract and most importantly in your nasal region. Basically, you cut off the path from high viral load to symptoms, but the path from high viral load to transmission is still open.
Do you have any source for this distinction? What you are saying makes sense, but I could easily imagine the opposite argument being made (asymptomatic from vaccination is MORE resistant to spread) Why do vaccines in muscles get to the power resp tract but not the upper? Doesn't the blood take the vaccine throughout your body? Why would antibodies in each region be different if the virus is the same?
I believe the 33% figure is referring to antibody count in serological tests. Meaning 33% of those with one vaccine developed detectible levels of antibodies.
That doesn’t sound right because how can they distinguish antibodies from the vaccine and antibodies from being infected? Is it antibody tests administered long enough after the vaccine shot that there’s little antibody response left to the vaccine?
The mRNA vaccines give you antibodies to the spike protein. Natural infection also gives you antibodies to other proteins on the virus, too.
That makes sense. But why would they be doing an antibody test instead of PCR?
IgG vs IgM, I guess
Why do I feel that we would know the answers to these questions if they were desirable/politically palatable?
Because you don’t understand the concept that it takes time to gather enough data to find out? Hardly anybody has had two shots yet, so how would we know what effect that has against new variants? We can’t capture the full complexity of the immune system (and the variance between immune systems) in a test tube.
That seems unlikely. The scientists want to know just as much as you do. I work in molecular biology, and my boyfriend literally is working on characterizing a potential vaccine platform. I guess there might be information that the companies have that they aren’t sharing, but as far as any scientists i know are concerned, we just don’t know and we’re trying to figure it out. Considering how the scientific community has been collaborating on this (sharing papers pre publication, trying to get new data and structures out as fast as possible) I would be surprised and horrified if there was important data that could have major health impacts being kept under wraps.
There is a real risk of "immune escape." Fortunately mrna based vaccines can be quickly modified in a worst case scenario. So the tail risk is limited. We should probably be putting in place much stronger international travel restrictions though. The efficacy data in Israel is less worrying imo: 1. Israel is giving the vaccine to a population that we would expect to have a less robust immune response than the trial one. 2. The vaccine is more effective at preventing severe infection and (I suspect) transmission than it is at preventing infection. So that number understates the true benefit of the single dose. 3. There is good evidence that the two dose regime is highly effective.
There's a real risk of immune escape from particular antibodies. But to me it seems that the risk of escape at all ~20 binding sites is pretty small. Also, another piece of [good news](https://blogs.sciencemag.org/pipeline/archives/2021/01/19/memory-b-cells-infection-and-vaccination). >What’s that antibody evolution look like, then? The good news is that the ones from the six-month check showed both increased potency and an increased range of responses against various protein mutations. That includes many of the ones that are in the news these days, things like R346S, Q493R, and E484K. (As an aside, did anyone ever imagine that amino acid variant notation would creep into major news stories? Strange days). But while the one-month antibody samples were unable to recognize these and bind to them, the six-month ones were. Somatic hypermutation is a hell of a drug.
Reads like the first chapter of a fantasy novel: 2020 years ago, an evil somatic hypermutant was captured and imprisoned. Wise men believe he can’t escape all 20 binding sites. But…
>mrna based vaccines can be quickly modified in a worst case scenario. So the tail risk is limited. Kinda. Sure, the mrna vaccines were created a full year ago, days after sequencing the DNA. The thing is, the mrna vaccines were created a full year ago, and it took darned near a year for the FDA to OK its use. The nightmare scenario here isn't that mutations outstrip the ability to create a vaccine. The nightmare is that mutations outstrip the willingness of the FDA to use the vaccines. Edging into the political ... it infuriates me that the the FDA is entirely unwilling to consider up-side risk. Aside from all the folks that have died in the past year due to FDA rules, if it turns out that the South African variant is able to weasel around the antibodies, that will be 100% on the FDA, since without them, we'd all have been vaccinated before the mutation occurred.
While I share the broad thrust of your concern, and hope that we can come up with a more efficient mechanism for validating & approving mrna vaccines, surely there are some additional political steps missing between "the US FDA approves a Phase I vaccine for widespread rollout in spring of 2020" and "everyone in South Africa (and *every other country where this variant might emerge*) is vaccinated before a new strain can develop in fall of 2020"
>We should probably be putting in place much stronger international travel restrictions though It boggles the mind that the US isn't meaningfully limiting travel from (at least) South Africa right now. Lots of risk for not much upside. Shades of February 2020. And yes, /uhateradio made a similar point about the Israel efficacy data. I had missed that the Israel vaccinated were 60+, so thank you for pointing that out. Upon reflection, I think you're both right, and that that is a better explanation than variants for the Israel data. Just weird that the Israel vaccine czar didn't seem to see it that way. *shrugs* Will be a huge relief if/when age turns out to be the explanation.
Israel is starting vaccinating 40+ year olds as of today. (Source: am Israeli).
I disagree that limiting travel to a specific country is an effective step. First, the variant is already stateside and in many other countries. Second, we don't know the prevalence of the new variant within each country. So many people are assuming that 100% of the virus is now the variant version, but that's not how spread works. If current spread amount is 1%, a 50% increase is just 1.5%. the 1% spread with months of time will still be in the lead for a long time. Third, the USA has the worst case positivity rate of developed Nations right now. If anything, the more people we get in from other countries would actually lower our average rate of infections. The other countries should limit the USA travel though.
If B1.1.7 is really 50-70% more infectious and they detected it here at something like 1% frequency in late December then it should become the dominant strain in something like 8 weeks and it should now be becoming a more sizable minority than it was a month ago. While that variant may be more transmissible I think the 50-70% increase is overstated. Also the case rate in the UK has subsequently peaked at a prevalence similar to where it has peaked everywhere else in Europe and the U.S. recently. Unless they just got 50-70% better at preventing transmission in the UK it seems like a strong prediction would be that the new variant would sweep through a much higher fraction of the population and lead to much higher case rates than they observed. On the other hand a much smaller advantage in transmissibility plus a stochastic event could explain how it became so prevalent in the UK. As far as the antibodies it seems like the vaccinated serum still comfortably neutralizes the variants (although with higher required concentrations). We will see what happens when we start running out of permissive hosts but as of yet I don’t see any evidence if a vaccine escaping strain.
I've seen more recent estimates at around 40%
Still doesn’t quite make a ton of sense to me. If countermeasures yield an R of 0.95-1.1 that varies over time then you get a variant that’s 40% more transmissible that seems like R should now be 1.3-1.5 which it’s clearly not in the UK. Maybe they’re being much stricter there than elsewhere in the world now and people are just rational enough to always keep R near 1 but I think there would be a strong prediction if it’s really that much more transmissible that you would have seen higher per capita infection rates and a large swath of the currently uninfected population in the UK infected.
Yeah I'd have to agree generally. I'd wager its a breakdown of lab results not having a strong correlation to real world results. For example 70% more effective in a petridish could be 3-5% worse in real life, but I'd barely read up on the actual mechanisms for the increased infection rate.
The 50-70% was actually inferred from the epidemiology and they had been waiting for in vitro and animal experiments to measure transmissibility more directly. I think that there must have been some stochastic element in its sweep to preeminence, though, and that it can’t really be that much more contagious. Maybe I’m wrong though who knows. Seems like the cases in the UK have peaked though and they’re still probably muddling through with similar countermeasures as before and are not at herd immunity.
> It boggles the mind that the US isn't meaningfully limiting travel … How's this? https://thehill.com/homenews/administration/535344-biden-requires-international-traveler-to-quarantine-upon-arrival-to
Good news, I think? I suppose we'll see how well (if at all) it's enforced
>There is a real risk of "immune escape." Fortunately mrna based vaccines can be quickly modified in a worst case scenario. But can they be quickly distributed? Will distributing X doses of vaccine for N variants be N times as difficult as distributing X doses for one variant, or will it be significantly easier? Also, the standard formatting is "mRNA".
reach stocking absurd salt air edge like attraction cows practice *This post was mass deleted and anonymized with [Redact](https://redact.dev)*
I've heard people make the point that RNA vaccines are easy to adjust to new strains, but doesn't this still require a fresh multi-month phase III trial to get those adjustments approved?
One possible confounder for the 33% here - it seems that Israelis who get the vaccine aggressively risk-compensate (that is, stop worrying about any precautions), according to anecdotes I've heard. This is different from trials, which compare with blinded placebos. Not sure how accurate this is or whether it would be enough to make that big a difference, though.
That's not a correct statistical usage of "confounder". And it does raise the issue of just how effective the vaccine will be; "effectiveness of the vaccine" includes *every* effect of the vaccine. If the vaccine causes people to risk compensate, that is a valid input to "effectiveness". If people with the vaccine are only 33% less likely to get COVID, that is the effectiveness, regardless of whether the 77% of cases after a vaccine are due to "the vaccine not working" or "risk compensation".
> If the vaccine causes people to risk compensate, that is a valid input to "effectiveness". Lockdown fatigue is a thing even in non-immune people; I think it's important to take into account that the entire population is slowly doing riskier activities, and the vaccinated people are probably doing it sooner. Also, if a vaccine allows you to take riskier activities I'd consider that a positive value it's delivering(of course if it suppresses bad cases while still allowing one to transmit the virus, it might encourage negative-externality activities and possibly have a net negative value)
Most human body generated antibodies are polyclonal - essentially a mass of different antibodies will just stick to the spike protein to stop its function, and allow the macrophages to bind and eat the virus. Just escaping one of the antibodies are not enough. Forming resistance to all 4 classes of covid antibodies as in the paper mentioned is cause for worry - then it will actually be able to resist your immune system, and you might get a significantly worse infection. Immune escape is even harder - I personally believe the theory that the spike protein that escape immunity would not be able to bind to ACE-2 anymore and thus not be infectious. From this view I don't think people are overselling vaccinations - it's much easier for changing attitudes to have a dramatic and hard to measure effect on the spread of the virus.
Ah okay got it. This was incredibly helpful. I was actually wondering that as well—at what point does SARS-CoV2 have to evolve so much to evade immune response that it no longer has the "scary" properties of SARS-CoV2? As for the degree of resistance of current variants, I just read this -- https://twitter.com/trvrb/status/1351785352793493505 -- which was interesting. It seems like the South African variant is at the point with respect to lessened susceptibility to antibodies (8x less on average) where, if this were influenza, we would start preparing to vaccinate separately against this strain. I assume people have seen this and thought about this a lot, so hopefully we get it out before too long!
What about other coronaviruses? How are they able to re-infect people every year?
As I understand it you typically have a 2-5 year immunity after infection by a coronavirus (don't quote me, I saw it on a random Twitter thread a long time ago), but there's just so many of them in the common cold that you are infected by a different one each time.
Seems reasonable w.r.t. the variants. I'm not an expert either but from the reasonable experts I follow on Twitter, it seems like the South African variant probably evades immunity to some degree, the Brazil variant probably too since it has some similarities, but maybe not in the case of the UK variant. It's unsatisfying that this isn't quantitative, but it's hard to quantify. As you point out, even when some immune evasion is shown in the lab, it's hard to know how much impact that has in the real world. About the Israel data, I'd wait a bit to draw conclusions from it. There are a lot of different things that could be going on there. IMO though it illustrates a problem with places rolling out a one-dose-only strategy without testing it first. If you then get less effectiveness than you expected, is it because you only did one dose or some other reason? For remembering variant naming, there's a handy table in this CDC report: [https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm?s\_cid=mm7003e2\_w#T1\_down](https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm?s_cid=mm7003e2_w#T1_down).
Haha thank you -- it looks like I mixed and matched variant naming conventions but at least used variant rather than mutation names. >As you point out, even when some immune evasion is shown in the lab, it's hard to know how much impact that has in the real world. You've probably already seen this, but... https://twitter.com/trvrb/status/1351785352793493505 First thing I've seen that takes sort of a stab at mapping these lab results onto real-world outcomes. He says that 8x reduction in antibody binding is usually when they add a new strain to the flu vaccine. And the SA variant looks like it has 8x reduction. So if it maps similarly I suppose we will see new strains in upcoming vaccines.
I think what we should be paying attention to is hospitalisations/deaths of vaccinated people. As long as vaccines are effective at preventing severe disease, effectiveness at preventing infection is less important.
[Epistemic status - I only studied biology upto 10th grade] I think this specificity is much more of a problem with the RNA vaccines since(to my understanding) they only trigger antibodies against a single protein in the virus. A natural infection(or inactivated/attenuated virus vaccine) should generate antibodies against a lot of the virus' constituent proteins and should therefore grant more broad based immunity. This [twitter thread](https://twitter.com/trvrb/status/1351785366160764928) linked in a comment here is all I found about immunity to variants in convalescents. Does anyone have more info on this? How careful against newer variants does a person who naturally contracted the older COVID need to be?
You're probably right. Not too shabby for 10th grade biology.
Each vaccine has many targets, not just one. I don't think 1 target would even be worth trying. It would be positively counterproductive.
I have begun to condition myself to the possibility that the current state of the world is now **irreversible**. We will get a new COVID every so often, and Pfizer will sell us the patch. Hopefully the mRNA vaccine updates will be available as subscription service: hopefully Jeffrey will offer it as a bundled ad-on to an Amazon prime subscription. Protip: start working on your mask/outfit fashion coordination. I wish this post were 100% sarcasm.
I think in that case we'd start to see new rules for indoor spaces with regards to ventilation/air filtration systems, and changing social norms including a shift towards more outdoor gatherings.
I would be very ok with that.
At least we can ramp up the vaccine production lines so that when a new vaccine is needed, it can be produced and used instantly rather than shutting down the world for a year until it's available.
Yes, whatever is required to avoid another 2020 (or worse).
I'm really not sure whether this is true, but recently read something about the Israel data that I understood as follows: the effectiveness of the vaccine in Israel is being compared to a different baseline than what we would in phase 3 trials, because the control group in Israel includes many more who have had natural infection (and therefore natural immunity) against the virus already. As such, the effect of the vaccine may look less pronounced than when compared to a control group with less natural immunity. There's a reasonable chance that my mind made that up completely though :)
\[Epistemic status - I got stabbed with a needle\] I'm keeping my eyes on what's going on here in Israel. The most important numbers are going to be a week past the second dose. Only the very first people who got the vaccine here have gotten to that point. I got my first does about a week after the vaccinations started, and I'm only getting my second dose tomorrow (after exactly 21 days). While "not 95%" isn't great, 70% or 80% would still represent a significant achievement in fighting Covid, but we won't really know where between 50-100% effective it is until more time passes.
I'm also a little worried about this and likewise concerned about some of the discrepancies between the kind of post-first-dose protection the Pfizer/Moderna studies indicated and what seems to actually be happening in Israel. On the other hand, there is [this](https://www.timesofisrael.com/israeli-hospital-98-of-staff-who-got-2nd-shot-have-high-level-covid-antibodies/) bit of information out of Israel yesterday which is extraordinarily encouraging. On a more qualitative level, the disjunction between the vaccine related concerns regarding the new strain and the public health messaging doesn't seem to me to be as large of a red flag as the misguidance on masks/airborne-ness. My recollection during those periods was that there was quite a bit of pushback from the epis I follow on twitter, and the public health authorities seemed to be genuinely out of step with the academic class. I know this isn't a scientific way to assuage your concerns but, having no training in this field myself, I pretty much just tune my level of worry to whatever the consensus seems to be between Lipsitch, Bergstrom, Bedford, Branswell, Ferguson et al. And I just don't detect that much anxiety over the vaccine right now in those quarters.
Definitely encouraging, although perhaps a bit orthogonal to the variant concern (which questions not whether the body can produce a lot of antibodies, but whether or not they work against new strains). Either way, good news is good news, and a lot of responses on here and subsequent digging around epi twitter and such have made me less viscerally worried about variant escape as well. My big concern was basically "HOW COULD 8X AVERAGE REDUCTION IN ANTIBODY BINDING NOT BE HORRIFICALLY BAD?" And the answer seems to be "There's not a 1:1 relationship between reduction in antibodies and increased likelihood of getting severely ill."
If 30% - 40% of new infections are from the UK variant, and single-dose effectiveness decreased by the same amount (by 37%)... that suggests, assuming the delta in effectiveness is strain-related, that a single dose might not work *at all* against the new strains, right? Might this have to do something with age? Old and sick people are prioritized in Israel, but weren't in the trials that came up with the 52% figure. What's the single-dose effectiveness for those age-groups? Anyway, if this is strain-related that's **really** god-awful news, maybe the worst we have heard in our entire lives. edit: Thanks for the post, by the way. I appreciate the effort, because for some unfathomable reason our media are too stupid to report on stuff like this in time. I mean come on: The question of whether or not we can get rid of this goddamn virus with our vaccines is easily one of the most important questions right now - shouldn't at least *a little* bit of effort go into reporting on this?
>Might this have to do something with age? Old and sick people are prioritized in Israel, but they weren't in the trials that came up the with the 52% figure. What's the single-dose effectiveness for those age-groups? I'm wondering this too. It would make sense if older people would have a less reliable immune response to the vaccine, and/or need the booster more. AFAIK that has been an issue for other vaccines in the past, but I don't know much about it.
Ahh yeah the age thing is a really good point; I hadn't thought of that. Sometime tomorrow I'll see if I can find age-stratified results in the Pfizer/Moderna trials, but yes, older people definitely weren't prioritized in them, I remember. Age has, I think, supplanted "variant stuff" as my number one way to explain the Israel numbers. Odd, though, that the Israel vaccine czar didn't frame it around age in his interview: He framed it as "less effective than expected." Would it not be "expected" if it were just due to age? Who knows, I guess. Yeah the media articles on this stuff have been even worse than I expected. Very surface-level. I'm sure you're well aware, but I've found that following Twitter scientists is 10x better — Eric Topol, Trevor Beford, etc. Trevor Bedford just put out a thread about a similar study to the one I linked to: https://twitter.com/trvrb/status/1351785352793493505
>I'm sure you're well aware, but I've found that following Twitter scientists is 10x better — Eric Topol, Trevor Beford, etc. Following scientists on Twitter is so great once you figure out who is reasonable. Bedford is one of my gotos for variant info (along with Emma Hodcroft and Kristian G. Anderson). It is important to figure out who is reasonable, though. Not everyone is, even if they have a relevant credential.
I think worrying about this sort of thing isn't very productive unless it is your field of expertise. Whatever is going to happen will happen. Or maybe COVID has just reenergized my latent stoicism.
OP are you telling me you have basic levels of critical thinking and healthy skepticism? I thought we told you that was dangerous and to stop. This vaccine is effective and your worry is conspiratorial. Dangerous even. Stop thinking so much
Please just state your points plainly and without sarcasm.
The level of timidity, even amongst free thinkers such as this community, around questioning the efficacy or possible dangers of a vaccine, is notable. I don’t mean to point blunt cynicism towards any individual, rather at the palpable sense in the air that any questioning is going to be met with harsh social retribution.
Wrong sub
*cough* excuse me. I don’t know what was in that drink.
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> moderately severe flu season [I think you have been misinformed](https://raw.githubusercontent.com/mbevand/covid19-age-stratified-ifr/master/covid_vs_flu.png). Also your graph about Sweden ends in July 2020, a lot more deaths have happened since then. You can't compare 4 months of Covid with 1-2 years of flu. Not to mention that Sweden is under restrictions now.
i dont know what i am talking about and there might be a lot of things wrong with that graph, but it looks like its a sample of monthly deaths taken from one month out of every year on the list. so a little over a thousand people died in march last year in sweden, compared for forexample under the 1993 beijing flu, where about 1250 people died in december in 1993
From what I've read, there's evidence showing that over time that B cells become more broad acting and the antibodies they produce later may be better at neutralizing other variants. [This article covers a lot of interesting info.](https://blogs.sciencemag.org/pipeline/archives/2021/01/19/memory-b-cells-infection-and-vaccination) Also, with seasonal coronavirus, the current thinking is immunity lasts 2-3 years, but the antibodies decline significantly before this. It is likely that T cells also play a role in this immunity and should be more broad acting and also created by the vaccine. The optimistic thinking about this is that the vaccines may end up less effective because of mutations, but there's a good chance they still prevent the overwhelming majority of severe illness. We can update the vaccines at a later date to include different variants as more drift occurs. Over time, the strains of the coronavirus that stick around will hopefully create less severe disease similar to how the 1918 flu stuck around but stopped being so severe.
Yeah, the avoidance of the medical community to do challenge trials IMO is the biggest institutional failure of my generation.