Lukas_Gloor

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Why did the UK switch to a 12 week dosing schedule for COVID-19 vaccines?

December 30th was shortly before the UK's third peak of infections, the one caused by the emergence of the UK/Kent/Alpha variant. The more infectious virus put the government under pressure to come up with good ideas to keep R down in the future. 

The UK also has a political tradition of scientists being closed involved in some policy decisions. (Another commenter mentions Cummings being involved with that, and that may be partly true, but I think the tradition to have scientists closely involved is much older.)

Covid 6/17: One Last Scare

I mentioned it as a consideration, but yeah, I'm probably underestimating the effect of that by a lot, now that I think about it. I wasn't sure how much the US has so far relied on the J&J vaccine, which is also less effective. But it looks like it's a low amount of it. 

Covid 6/17: One Last Scare

Regarding the estimate that Delta is 40% more infectious than Alpha: I've seen 50-60% mentioned a lot in the last couple of days from UK expert sources. If true, this would probably make a big difference to your calculations. 

Covid 6/17: One Last Scare

Thus, it looks clear to me that most places in America are going to make it given the additional vaccinations that will take place, but some places with low vaccination rates will fall short. 

I found myself intuitively skeptical about this claim and tried evaluating it via a different line of reasoning than the one you used (but relying on some of your figures). After going through this, I mostly updated that it will be a close race with the vaccinations. Overall, I find it 65% likely that places with a roughly average vaccination coverage in the US won't be able to avoid large surges in case numbers (defined by either lockdowns or really strong new restrictions, or 3% of unvaccinated people infected at the same time.) (This could be compatible with your estimates, because the death rate in well-vaccinated areas would still be relatively low if vaccination uptake is high amongst the elderly.) What seems very clear is that locations with below-average vaccination coverage will be in trouble.

My approach and estimates:

I think a crude lower bound for when you get Delta variant under control is when you have a substantially larger percentage of the population vaccinated than the UK currently has. (Because R is 1.1-1.35 in the UK now and that's before the full reopening.)

Current vaccination percentages for the UK (all age groups):
63.3% first dose
46.0% second dose

Current vaccination percentages for the US (all age groups, I think): 
52.7% first dose
44.1% second dose

You say there's about 25% Delta variant in the US now.

5 weeks ago, I commented that the UK had >50% Delta variant in some areas. With a doubling time of roughly 11 days in the UK, it must have been at 25% roughly 7 weeks ago. Meaning, assuming that the infection levels in the US currently are comparable to what they were in the UK 7 weeks ago, then the US is roughly 7 weeks behind the UK timeline. 

7 weeks ago, the UK was reporting around 2k Covid cases (with a population of 66 million). The US population is 5x larger. The US is presently reporting around 13k cases. That's similar enough! Therefore, I'm going to operate under the assumption that the US is "7 weeks behind the UK timeline." 

The situation in the UK is concerning and getting worse still, but the case numbers are substantially below the previous peaks. I'd say the UK is about 3-4 weeks ahead of things getting very bad.

By that reasoning, the US has roughly 10 weeks to get R below 1 for the Delta variant.

You say,  "Currently [the US] are vaccinating about 1% of people each week." 

I'm assuming that's both doses?

Continuing with that, in 10 weeks, the US should have the following vaccination percentage:

62.7% first dose
54.1% second dose

And here the present UK numbers again:

63.3% first dose
46.0% second dose

The UK is not fully reopened yet, and R is at 1.1-1.35. Most UK experts are pessimistic about things getting better anytime soon, despite vaccinations progressing quite quickly.

That said, the second dose may matters more than the first dose, especially if the first dose is Astra Zeneca. So, 54% second dose instead of 46% should make quite a large difference. I think (?) the US also relies slightly more on Pfizer and Moderna than the UK, which should add a bit of extra protection. Summer temperatures also help out. But is all of this enough to put R below 1 (for the Delta variant, specifically) early enough?

The UK isn't even fully opened yet.  Some US states may go ahead with the full reopening now, in which case they'll have less than the projected 10 weeks until they catch up with the UK timeline. 

Then again, there's room for the vaccinations to speed up (the vaccination rate used to be higher at points in the past).

Note that my definition of "large surges in case numbers" isn't necessarily that bad. 3% of unvaccinated people infected – the UK is almost there already, and deaths are extremely low because the unvaccinated people are mostly really young.

Update: I'm realizing that country-wide infection counts are driven mostly by the places with the worst vaccination uptake, so a location with an average vaccination rate wouldn't be hit that badly compared to the country average infection rate. This means I'd now change my operationalization to something like "worst 25th percentile." And maybe make it 60% instead of 65%. 

Covid vaccine safety: how correct are these allegations?

One obvious candidate explanation: For the reason you explain in the letter to your dad – probably those deaths were roughly what you'd expect among the vaccinated demographic if the vaccine is benign. By contrast, the specific blood clots are generally rare. 
 

Which rationalists faced significant side-effects from COVID-19 vaccination?


If you believe that we should expect a certain number of side-effect reports even if there's no issue with the vaccine (and reacting it would mislead System 1), how reports of significant side-effects do you think we should expect?

Are you asking for effects that show up after 3 days (and then don't go away), or anything bad that happens sometime within a couple of months after getting vaccinated? 

If it's the latter, then among1,000 people you might expect that a few people will have weird health issues show up without an obvious cause. I'd be surprised and pretty concerned if someone died in that interval (for non-obviously traceable causes), but if it was just a handful of issues of the severity of "developing a kind of serious new allergy" or "developing heart rhythm issues," that could be entirely what's expected (though I haven't studied the frequencies).

With miscarriages, for instance, apparently "1 in 8 pregnancies end in miscarriage" – so out of a large enough pool, you have to expect that someone had a miscarriage in the last couple of months, etc. 

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My father, mom and brother had no significant side effects after two doses of either Pfizer or Moderna. I'm only 3 days after my first dose of Pfizer; no side effects so far.

My father's a GP and seemed happy that I'm getting vaccinated – though he did say that it's possible for young people to have "kind of scary 2 days," side-effect-wise.

(Also have friends in the community who didn't have issues from 1st doses, but was focusing on people outside.) 

AGI in a vulnerable world

I guess you are more optimistic than me about humanity. :) I hope you are right!

Out of the two people I've talked to who considered building AGI an important goal of theirs, one said "It's morally good for AGI to increase complexity in the universe," and the other said, "Trust me, I'm prepared to walk over bodies to build this thing."

Probably those weren't representative, but this "2 in 2" experience does make me skeptical about "1 in 100" figure.

(And those strange motivations I encountered weren't even factoring in doing the wrong thing by accident – which seems even more common/likely to me.) 

I think some people are temperamentally incapable of being appropriately cynical about the way things are, so I find it hard to decide if non-pessimistic AGI researchers (of which there are admittedly many within EA) happen to be like that, or whether they accurately judge that people at the frontier of AGI research are unusually sane and cautious.

Looking for reasoned discussion on Geert Vanden Bossche's ideas?

As an example, look at E484K - this mutation changes the amino acid polarity, so that antibodies trained against the E variant will have a much harder time attaching to the K variant.  If an antibody fails to attach, it doesn't 'crowd out' anything.

That makes sense; I was wondering about this exact thing. It seems like VB is painting a worst-case scenario where a bunch of things go wrong in a specific way. Perhaps not impossible, but based on what you're saying, there's no reason to be unusually concerned. 

Looking for reasoned discussion on Geert Vanden Bossche's ideas?

Nice, that's reassuring. I assumed that claim (2) was basic immunology because he was talking about it so confidently, but at the same time, I noticed confusion about the lack of precedents where outdated antibodies (from previous infection or outdated flu vaccines) cause complications. It seems like immunologists think his view on (2) are outlandish – in which case, "case closed, nothing to see here." 

Edit: On the other hand, reading this blogpost makes me think that the mechanism Vanden Bossche proposes is plausible at least in theory. But also, the Nature blogpost discusses that targeting the spke protein in particular was a good idea:

Targeting the Spike protein is another big benefit that we got from the earlier SARS work; which suggested that (for example) targeting the Nucleocapsid (N) protein was riskier. With the Spike, you put the virus in an evolutionary tight spot: evading the antibodies while trying not to lose the ability to bind to the human ACE2 protein. So far, that looks like too narrow a path for the virus to stumble through.

So far, that all seems right and the vaccines continue to be functional enough to neutralize even the most vaccine-resistant variants.

Looking for reasoned discussion on Geert Vanden Bossche's ideas?

At 1:40:22, he claims that we see young people without risk factors getting severe Covid for basically the first time only now, because they get infected in the time window right after vaccination when their antibodies are immature and only serve to crowd out innate antibodies. 

That claim sounds dubious to me! Firstly, there's always been a (small) risk for young people to develop severe Covid. The way both he and Weinstein talk about "young people are already immune" seems a bit dumb to me. Secondly, if getting infected right after vaccination increases a young person's risk, that would show up in the data. But no one is talking about this yet. Am I missing something? 

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