Post#1455 » by Captain_Caveman » Wed Dec 23, 2020 7:16 am
Thoughts from a smart friend on the vaccine aspect of stuff:
(1) we need to get some terms defined:
protective or clinical immunity --> this is preventing you from getting sick ... this is where the vaccines showed 95% efficacy (the trial endpoint was infection + symptoms ... so if you had infection but no symptoms, you were still counted in the win column) ... the question of could you get infection but no symptoms wasn't directly studied, though Moderna study had very suggestive data (more on that in a second) (2) sterilizing immunity --> this is preventing you from getting infected at all ... as mentioned, this was not directly studied ... BUT there is AMPLE evidence that the vaccines WILL prevent infections and transmissions to at least a moderate degree: - Moderna did a smart thing and they swabbed everybody at the time they administered the 2nd vaccine and there were ~60% fewer asymptomatic infections in vaccinated individuals (3% vs 1% or something in that ballpark)... and that is after the first dose, very likely even better after 2nd dose - AZ/Ox studied asymptomatic infections in one of their studies and found about ~65% sterilizing immunity - Animal studies showed some degree (though not 100%) of sterilizing immunity ... and SIGNIFICANTLY reduced viral shedding which would imply dramatically reduced transmissibility (more on that below) - Thus, data that there will be significant sterilizing immunity exists ... but likely not at a 95% level - data seem to be converging around the 60-70% level
(3) reduced transmissibility --> this is, even if you are asymptomatically infected, you will be much less infectious - so it isn't full sterilizing immunity, but you will be asymptomatic, and you will have much lower viral loads / viral shedding - so when you talk, cough, sneeze etc you are putting out way way way less virus ... this was seen very clearly in the animal data and is also kind of a "first principles" thing (4) in sum - the best guess consensus right now is something like: 95% clinical immunity 60-70% sterilizing immunity ~75% of people will have dramatically reduced transmission (either due to sterilizing immunity or get infected but way lower viral shedding) but this will likely be a continuum we will learn more i'm sure about how these numbers exactly shake out, but this is the ballpark to expect THAT IS REALLY REALLY GOOD. It is a myth that all vaccines provide 100% sterilizing immunity - this just doesn't always happen. We could have EASILY been in influenza world, where all you get is 50% clinical immunity - anyone poo poo'ing this vaccines efficacy is just so off-base - this is far better than any expert would have hoped - also, it is very cray cray to say "this isn't really a vaccine" lol - you can say "this didn't turn out to be a magical 100% sterilizing efficacy vaccine" - ok, sure ... this is far better than experts were thinking we'd get (if i get to it i'll post a good review article summarizing all vaccines: it is a myth that all vaccines provide 100% sterilizing immunity - some do, many don't - many provide some sterilizing immunity but not total, etc. etc. - this is all very normal vaccine stuff)
now, it is totally true that the messaging has been bad and that 60-75% is not 100% --> therefore, it is absolutely right to say "nothing really changes until 70% of people get vaccinated (or prior infected) and case rates get really small" --> wear masks, socially distance, increase air ventilation, crowds and indoor activities should be curtailed ... this is until a sizable % of pop has immunity and/or case levels drop ... because yes, some (probably not most) vaccinated people will still be able to transmit the virus - and yes, the messaging on this has been bad - people following this closely have known this was likely to be the case honestly since april based on the animal data ... but yeah, overall education has been not great, but c'mon: we've only actually been vaccinating people for like a **** week lol - and we have no functioning federal government - give it a little time, we'll get the message out [side note: this is where we can also make a quantum leap forward with at-home, cheap rapid antigen testing - the technology exists for $5 at home 15 minute antigen testing with very good sensitivity/specificity - now, if you've had the vaccine and have a negative test, you are basically 100% home free ... almost all experts say these tests should have been deployed at scale months ago - and Biden has signaled this will be a priority (why we don't have this yet is very interested but is a whole other thread) ... so i think if we add mass scale at home rapid testing, (plusl normal spring ebbing) we could get back to very close to normal by april/may]
(5A) scary mutations ... a few initial points: mutations happen all the time with all life - this is normal ... small mutations in viruses = variants, larger & growing in prevalence = family/clade .... even larger = strain ... (5B) evidence exists, though it is not conclusive, that some of the new variant families do have higher transmission ... there is no evidence that it has higher mortality and no evidence that the vaccines won't work against these variants... in fact ... (5C) there is good data that the vaccines WILL work against these variants - pfizer has said they are currently testing against this variant but they have tested against 22 other variants and it has worked against all ... Eli Lilly said their monoclonals work against this variant as well ... there is also ample 3D structural biology that says that the antibodies produced by these vaccines will be able to bind to a large range of spike protein mutations ... and if the spike protein mutated to evade the antibodies, there is a good chance they will have a much harder time infected cells via ACE2 (5D) it is not impossible however - spike will probably over time see 'antigenic drift' and COULD mutate such that vaccines would have lower efficacy ... so it is very likely that we will have to make new versions of this vaccine over time ... this isn't for sure: it is possible that this vaccine will be very efficacious against all spike mutants - we just don't know ... but in the scenario where there is significant antigenic drift, it will not be that hard to make a tweaked version every couple years (mRNA platform will make this pretty easy)
(5E) so in summary on this: yes it is concerning, yes it bears close study (which is happening), but there is no need to freak out - the vaccine will almost certainly be very very effective for almost all people in 2021 ... but i don't want to be fully a pollyanna here - this bears close watching for sure
(6) quick bullet on safety .. this vaccine is very **** safe lol ... most significant side-effects in vaccines are seen within 1-2 months after administration - i don't exactly know why but i've seen that quote from 10 experts .. and we've seen NOTHING so far ... it has common mild adverse events, about twice as bad as flu vaccine and on par with shingles vaccine ... but it is pussy stuff to worry about that .... also the allergic reactions have been self-limiting (i.e. they are treatable and go away) ... unlike flu, definitely wait 15-30 minutes before you leave after the shot ... is it possible there will be some 1 in 100,000 rare side effects that could come out? yes, absolutely ... but this is in "struck by lightning odds" territory, and far far better odds than COVID - without vaccine, eventually 70% of people will get COVID, 0.5% of those will die, and some significant % will have significant long term morbidity ... no brainer
(7) there is very little doubt among experts that that the combination of natural immunity + vaccines (plus normal reduced transmission in spring/summer, plus better mask messaging, plus hopefully wide-spread rapid antigen testing) will bring us back to near-normal somewhere between april and november, with most guesses may-august ... we will be near 100M natural infections around march/april ... and if we vaccinate 100M by april/may, which is i believe still the target, even if there is only 65% sterilizing immunity and 75% significantly reduced transmissibility, we will be approaching the herd immunity threshold even around may ... won't get all the way there until later in summer/fall, but enough that case levels + deaths will be getting very very low
(8) that is not to say "this is 100% over and done forever" - it is correct to say that we will likely be in a world of watching for variants/mutations, tweaking the vaccine, contact tracing mini outbreaks in random rural areas, etc. for years to come ... but life will be mostly back to normal by end of the year at the latest, and probably by mid to late summer, with the trend lines hugely positive in the right direction by ~may
(9) ah yeah should have mentioned kids ... yup, right now only approved for 16/18+ ... both companies i believe (definitely pfizer) now has studies under way in i believe 12-18 ... no one has started any studies in under 12 yet, at least as of a few weeks ago when i looked into it ... yeah, i think a few things on this: (1) by the end of next year (probably more like summer) we will likely have an approved vaccine for 12-18 (2) by the time the aug/sep school year opens up, we will be at or very close to herd immunity - we will be approaching <5000 cases per day, all teaches will have been vaccinated, and very likely we will have widespread rapid cheap antigen testing available... that in and of itself will be enough for there to be a near-normal, very very safe school environment (3) you'll think i'm a right winger ... but it is 100% true to say that this virus is INCREDIBLY SAFE in people under 18 and even and even more under 12 ... like, literally safer than flu ... so once all the adults are vaccinated or immune, it isn't that big a deal for some kids to keep getting infected .... yes, there will be a few horrible cases where a kid gets very sick or dies .... but we are literally at flu (actually literally safer than flu) levels in kids ... i know someone will say "long-term impact of asymptomatic infection isn't known in kids" ... yes i guess that is true ... but i think the general consensus is that really isn't a big concern: we would have seen more of that already if it was going to be a big deal
