Delta Strain: Fact Dump and Some Policy Takeaways

post by Connor_Flexman · 2021-07-28T03:38:34.455Z · LW · GW · 60 comments

Contents

  Summary
      Delta vs originals:
  Parameter estimation:
    Cost of getting Delta:
  Policy Principles:
    Policy summary:
None
60 comments

Curation notice by Raemon: Curated. It seems really important to figure out how to deal with the Delta variant, and how to interface with covid variants longterm. I appreciated this post for:

1. Striking a good balance of presenting current facts on the ground
2. Noting where assumptions lie
3. Being clear about it's epistemic status, while
4. Aiming to be useful in the immediate term.

---

(Not a doctor; merely extrapolating lines of reasoning where they will go; all policy “recommendations” are entirely hypothetical and not actual recommendations; I rushed to finish this while it's still useful and relevant, so errors will exist and I apologize for the style)

Summary

As many of you know, the Delta strain of COVID is basically upon us. In the Bay, as of a few days ago, about .4% of people had it (based on .1% confirmed cases).

Currently it's doubling every week or so, but it's surprisingly difficult to tell if it will be a small blip or a huge wave. The main reason it's hard to tell is that it's entirely dependent on human behavior, which could change quickly if people become scared or if the government institutes rules again. The second reason it's hard to tell is because of mixed evidence on the difficulty of reining it in—while different studies makes this look more or less difficult, India and the UK both appear to have successfully done this without obviously draconian behavioral interventions. Berkeley might easily peak at 1% and drop back down, but for this post I'll be talking about policies for if we get a large wave.

We also don't know very much about vaccine efficacy against Delta. We know that the good vaccines reduce your risk by about 60-90% compared to without the vaccine, but the error bars are extremely large on all these studies. In part this is because it's so hard to disentangle effects from different strains, behavioral change in the vaccinated, social bubble effects, etc. Further, it doesn't answer the important question of whether this means ~80% of people are totally safe, or if it means that standing a few feet closer to people than you do now will cause the 5x difference that moots your protection. (This also plays into the above issue of predicting whether we will have a large increase or not.) 

That being said, we can still roughly estimate risk from definitely having Delta. A healthy 30yo probably has about 4x (3x-10x) less risk than before, due to vaccination, despite Delta causing higher mortality. It almost entirely comes from Long COVID. In absolute terms this is ~4 expected days of life, plus 1/200th of your future productivity and vitality. You can shorthand this to about 1-4 weeks of life lost if you expect to otherwise live a full life—obviously, it costs less if you expect to live less less time. This translates to microCOVIDs at roughly 1 hour of your life lost every 1k-5k uCOVIDs. Risk of death goes up by 3x for every decade in age, but Long COVID probably only scales at ~~1.5x per decade, so for people over 60 mortality starts becoming more relevant. All these calculations are "creative" so please don't take them as definites.

By default it will probably take 3-12 months for this to resolve. I strongly believe we should not lock down again for this long—I think we need a return to some level of normalcy [LW · GW], plus the risks are much lower than before. I don't strongly advocate for a single policy in this document, since I don't know what other people's risk-tolerances are, but I do give a number of principles. 

Personally, I am going to prioritize protecting the vulnerable—people with immune disruptions or age. I am probably going to advocate for them to get third vaccine shots [LW(p) · GW(p)] of a different brand, if possible and if the downsides aren't too down. I also am going to start running the numbers on what a variolation scheme might look like this time around. I also am hoping that tight-knit communities of responsible people can beat out trivial inconveniences and put the requisite effort into creating safe spaces for socializing with tolerable risk levels—this is very prosocial, both figuratively and literally.

Delta vs originals:

• Clearly spreads faster and has immune escape
• Getting big in many different countries places, moving fast enough that simple behavior changes don’t seem like they’ll bring R back <1, but significant ones might
• Maybe 2x the mortality
• Heads up that we’ve added to the common symptom list sore throat and headache, and removed cough. Gastrointestinal issues also are increased in likelihood with Delta. (A source)

Main sources I used:

• 126 early well-traced cases of Delta in China: Jing et al
• Summary of the Delta situation, Tomas Pueyo

Supporting sources:

• Serial intervals compared to original strain
• Lancet article on Scotland
• CDC tracker of variant proportions

Parameter estimation:

• Serial interval: 4 days median/avg, usually 80% within 2-6?
  • Probably shorter interval than initial wild-type COVID, though disputed: Jing et al shows medium evidence for, Pung et al shows weak evidence against—the difference comes from which dataset they compare against, where Pung uses Apr 2020 Singapore (which apparently had not a lot of lockdowns), and source 1 uses “the 2020 pandemic” (which probably had more lockdowns), and it’s unclear which we should realistically be comparing to since there is such a spectrum. But the higher viral load supports shorter serial interval
• R: maybe 4?
  • People are saying 5-9, but I think that’s unadjusted for difference in serial interval; if interval is 4 instead of 5.5 days, this would mean that reported R of 7 would turn into R of 7^(4 / 5.5) = 4. On the other hand, maybe reports of R are based on actual tracking, in which case you wouldn’t need an adjustment. Could use more research
• Viral loads are 1000x as high at time of testing for Delta compared to 19A/B variant, acc to Jing et al
• Fraction delta as of 7/17: >83% of US cases, acc to CDC tracker
• Mortality/morbidity/badness: 2.5x? 2x compared to Alpha strain (already 1.5x as bad as original becomes 3x as bad) according to Scotland study, 2x compared to original acc to Canada study which reports on mortality, ICU admission, and hospitalization, roughly x2 x3 x2, but basically within error bars of all being x2.2. Yale mentioned that other data have failed to substantiate this, but A) they don’t cite it and B) I don’t really trust numbers showing no difference here, because vaccinations will obviously drop mortality a ton making it hard to see an *increase*, plus the vastly increased viral load theoretically should correlate with higher mortality
• Vaccine protection: All these studies are trash, but very roughly 80% efficacy from Moderna/Pfizer. (I’d put 90%CIs roughly within 30-80% all cases, 60-90% symptomatic, 80-95% hospitalization, 85-97% mortality.)
  • Healthline reports on some stuff: one study says Pfizer is 80% against infection, 90% against symptomatic, and 95% against hospitalization. If you extrapolate to 97% against death, this would be about 1/30 the expected 2% rate = .06% mortality once vaccinated. However, the actual study seems terrible, with massive error bars, and claimed OR/HR of like 50% vs wild strain despite 90% “effectiveness”, so clearly I’m confused. Some sources say no additional protection to mortality given symptoms; probably not true but not disproven, could use more research into those
  • (They report some more studies too; Study 4 agrees, Study 5 says vaccines perform worse but it’s speculated that this includes more asymptomatic cases than normally included, Study 3 says vaccines slightly better, Study 2 is lab titers and not relevant to the wild.)
  • New Israel study [bad cite] says even less protective (down to 40% from 65%), but still 88% against hospitalization and 91% against severe illness
  • Moderna studies are even worse than Pfizer (but show ~~roughly similar results), and AZ and J&J are obviously worse by 2-4x or something

Cost of getting Delta:

• Rule of thumb: for 30yos, mortality pre-vaccine-pre-delta was .02%, now it’s .004%. That’s 40 micromorts or 1 day of lost life. [If the mortality/hospital protection numbers are wrong, at most multiply all these risks by 3 for 3 lost days; still pretty low]
  • Let’s say Pfizer offers 95% protection against mortality like they say it does for hospitalization. Since that’s including “protection via not getting the virus”, and protection from being infected is only 80%, this would mean that protection once infected drops death by about 4x. That implies a 30yo would have, instead of .04% mortality from Delta variant (.02% * 2), now a .01% mortality. However, it’s probably even more effective in the young (like how we saw it ~~5x [LW · GW] more effective in the young against the original virus), which could take 30yos down to .002% mortality. On the other hand, it seems like this is *too* low—someone’s gonna be immunocompromised or have failed to get the vaccine fully injected or something, so it seems hard to bound it much lower than maybe .004%.
  • 40yos should have .14% mortality from Delta, .036% after vaccine basics, down to .012% if vaccine effects are age-adjusted
  • 50yos should be .4% mortality, .1% after vaccine basics, down to .06% if age-adjusted
  • 60yos should be 1.4% mortality, .36% after vaccine
  • 70yos should be 4% mortality, 1% after vaccine
  • 80yos should be 14% mortality, 3.5% after vaccine, maybe 5% adjusting for age
• That means Long COVID becomes the dominant factor.
  • This is hard to calculate even roughly—here (h/t Anna Ore) is a good document with a roundup showing most studies are weak, which makes the important point that much Long COVID research fails to make the important distinction between that and lingering acute symptoms. Further, most of the studies claiming neurological issues after COVID don't JUST MEASURE IT for us. Please, someone, measure this. Anyways, we will continue to calculate it roughly:
  • Datapoint 1: My previous best analogical calculation said it was ~2x as bad as mortality (basically equating it to severe pneumonia [LW(p) · GW(p)] in long-term-effect multiplier) and my intuition says now it’s maybe ~~5x as bad, partly because mortality seems to have dropped faster than less severe afflictions. This would take us to .02% mortality equivalent, or 200 micromorts and 4 days of life when you get Delta.
  • Datapoint 2: A rough end-to-end calc might go as follows. For Delta, Pfizer reduces likelihood of symptoms given infection by 2x, hospitalization given infection by 4x, so let’s say 3x for Long COVID given infection. Let’s wave our hands wildly and say 5% of 30yos who used to get COVID would get it Long, which now becomes 1.5%. Let’s say this averages 1% hit to health permanently, since the effect is pretty huge in some people but we’re including lots here since we claimed 5% of 30yos were getting Long COVID before. This would mean 1.5% times 1% is .015% mortality-equivalent, which is 150 micromorts, which is 3 days. Big error bars on “1% hit to health”, obviously, but if you say it was 5x this bad you’re probably pushing at the boundaries of possibility (5% permanent loss of health to 5% of 30yos!) and EVEN THEN you’re still only looking at 2 weeks of life lost. This could use more research.
  • Datapoint 3: Study (h/t Daniel Kang) finds 20% of hospital workers with breakthrough infections have persistent effects at 6 weeks, though it says most cases are mild or asymptomatic. Given that a previous study finds healthcare workers have 7x more severe cases, I think this is fine news and fits with the above analyses. E.g. if you irresponsibly scale this down you'd have 2.7% of cases with persistent effects at 6 weeks, and even fewer at future times.
  • [Edited] Datapoint 4: Lancet study (h/t habryka) on cognitive deficits from COVID gives clear numbers, even if the methodology is suspect as usual.
    • Methodology: Aside from it being observational and thus having an obvious selection effect for who gets COVID, the main issue here is that the timescale of the cases is unclear. All measurements being finished by Dec 2020 means tests probably averaged about 3 months after infection (maybe it says this in the paper, but I didn’t see it). So, this is partly measuring effects that will disappear after 6 months. Zvi has good discussion of further methodology issues here [LW · GW], though my stance on most of them is "probably not a huge effect", and I'm just trying to get an estimate within a factor of 3 or so. Some supporting evidence that the study didn't go too off-the-rails: ARDS survivors, who usually get ventilated, show about a 13-point IQ immediate IQ loss that drops to 6 points after a year and stays that way through year two. That's a 1.5-2x larger effect than in this study, which passes the sanity check.
      • Anyways, raw data says reduced SDs on cognitive tests were
        • .04 for non-respiratory symptoms (.5 IQ)
        • .07 for respiratory symptoms (1 IQ)
        • .13 for medical assistance at home (2 IQ)
        • .26 for nonventilated hospitalization (4 IQ)
        • .47 for ventilation (7 IQ)
      • Long-term adjustment: We can reduce these by a factor of 2 for recovery over time, as was shown in the ARDS study mentioned above [ETA 8/27: and confirmed in a study on COVID survivors with 6- and 12-month follow-up, h/t Ray Taylor]. This correction is also supported by the dropoff in morbidity risk over time [LW(p) · GW(p)] from pneumonia cases with sequelae, which shows some different long-term symptoms dropping off on the year-ish timescale.
        • .02 for non-respiratory symptoms (.3 IQ)
        • .04 for respiratory symptoms (.5 IQ)
        • .07 for medical assistance at home (1 IQ)
        • .13 for nonventilated hospitalization (2 IQ)
        • .23 for ventilation (3.5 IQ)
      • Vaccine adjustment: the 3x risk reduction from the vaccine vs Delta can be taken in the same way as Datapoint 2. First, we need to know the average IQ effect though. My guess is that the median 30yo who gets Delta is asymptomatic, but that the average is somewhere between non-respiratory symptoms and respiratory symptoms (however, super hard to do this integral, and a surprising number of young people are hospitalized…). This might put average IQ loss at about .4. Reducing by 3x for the vaccine gets us to an average IQ loss of .15.
      • IQ affects many things. I'll use income as my primary proxy for full effect: if you roughly double your income when you go up 60 IQ points, each IQ point is about 2% added income. Outside of income, each IQ point is probably also .1% happiness (.01/10), and reflects some underlying worse health that may have other affects, etc. It’s hard not to overcount when something is correlated with everything. However, I think the largest effect here will be the money-equivalent (impact, perhaps). We can double this at the end to account for other effects. Giving up 1/50 of your productivity for an IQ point is equivalent to a lost week of production every year, which, while not the same as lost life, is still pretty bad.
        • Sanity check: why does Long COVID affect your brain so much, even if you have few other symptoms? Cognition does seem fairly afflicted by environment and things (lack of sleep, eg), such that small amounts of swelling may throw it off more easily than the rest of your body. This does somewhat fit with how impossible it is to do hard cognitive labor while sick (though doing physical labor is similarly bad...). I'd say this reasonably passes.
      • From this study and the supporting points, I would then guess that the average 30yo who gets COVID has their productivity reduced by on average .3% due to long-term IQ loss affecting productivity. I said I'd double this to include all other effects: so .6% life-equivalent is about 1 day of productivity loss a year in perpetuity.
• Altogether, this means in expectation you maybe lose 4 days of life and 1/200th of your productivity and vitality forever. The latter is about 1 day per year of lost productivity, which translates to probably 1-4 weeks of lost life-equivalent. (NB while these are large costs, remember that not exercising costs you at least 10x this amount.)

Policy Principles:

Principle: Lockdowns last time were too strong

• Being a few feet closer to someone is an order of magnitude more virus. Many activities are OOMs different in their risk, as confirmed by Microcovid.org. Lots of risky people didn’t even get the virus; if they had 50% likelihood of getting it per year, then safe people at 3 OOMs safer were likely being too cautious
• Microcovid says you can do more than most of us were doing
• Filter bubbles are strong. I think this is a main reason that no one I know who was being "reasonably safe" got it, and why I know upper-middle class people who took a number of risks and still didn't get it.

Principle: We don’t know the endgame

• “[Booster trials may start as soon as August]”, so boosters won’t be here for months, and might again take many months after screening to actually get distributed. If the initial vaccine took 6 months to screen and 6 months to distribute, my guess is they could speed it up to possibly 3 and 3, but that’s still 6 total months until we’d get to escape
• Without boosters, it could take 4-12+ months to either reach herd immunity or keep rates consistently low, if we bounce back and forth in waves like last time

Principle: Very hard to predict the control system

• This means it’s very hard to know whether things will be bad a month out, for example
• The control system does clearly take forever to play out to herd immunity though

Principle: Tests still suck

• People continue to act as if testing is a solution, but even PCR test only give about one bit of evidence. False negative rates are often about 50%, only going down to 25% at peak load [ETA: this study (I've lost the link and only have a picture, which I don't want to dump in here) probably slightly overestimates: after looking at much more evidence, incl in the comments here, I now think it's about 30% FNR typically and 10% if you do it at the right pre-symptomatic time; eg here (h/t Shaun Pilkington) says "approaching 80% sensitivity"]. The statements that PCR tests are 99% accurate is, as far as I can tell, a simply false extrapolation from other domains or from studies in overly synthetic laboratory conditions. Further, I expect that false positives are very correlated, so you can’t just test yourself 5 times and get 5 bits of evidence.
• Rapid tests are even worse, <50% sensitivity unless they’ve gotten much better in the last 6 months
• It’s very hard to make a coherent strategy out of testing when people have about half their infectiousness period before they can test positive. This is even worse with Delta, where viral load is 1000x as high at first positive test, and the whole timeline is accelerated by a factor of about ⅔.

Principle: No one knows how to interpret vaccine “effectiveness” into the quantity we care about

• “Effectiveness” currently means something like 1 - Relative Risk. Imagine two worlds that would both give rise to vaccine eff of 90%. In the first world, the virus gives perfect immunity to 90% of people and no immunity to 10%—so if a megadose up the nose to the 90% still wouldn’t cause sickness, and a single virus in an aerosol drop would make the others sick. In the second world, the virus is about 90% effective warding of the “typical dose”, maybe 10^4 viruses on your mucus membranes. But if you give someone a 10^5 dose, they’d get sick, and a 10^3 dose they wouldn’t get sick. It’s just that right around 10^4 is the dividing line given your body’s innate immune defenses. 
  
  Both of these worlds would show 90% "effectiveness, but for two different reasons. In one, all the variance comes from immune responsiveness. In the other, all the variance comes from environmental stochasticity, mostly from viral load. Currently, effectiveness numbers themselves give us no evidence for where on the axis between these worlds we are. Yet each have VERY different implications: if it’s entirely dependent on innate responsiveness, healthy people basically shouldn’t take protective measures since everyone’s going to get a small dose eventually, and it’s unlikely that you’re in the “definitely will get it” category. If effectiveness varies entirely with environment, you can never be safe, and acting normally is bound to eventually get you in contact with a 10^7 bolus that gets you very sick. (So we’d really prefer the world where variance is explained by immune responsiveness.)
  
  We do have some evidence about where we are on this axis between the worlds. There are studies which find pretty big differences in level of antibody titer produced by the vaccinated, and in some cases where they have almost no antibodies it’s pretty clear that this means immune responsiveness is going to be at fault when they get sick. And I think there are studies finding correlation between titer and effectiveness. Both of these point toward innateness. But we also know that it has to be true that for many of those with low levels of antibodies, a larger dose will push them over the edge. There is also slight evidence from the Israel numbers, which give effectivenesses that vary some over time, that there’s a serious behavioral/environmental component. I don’t know of any good numbers personally, and it will be a question of distributions anyways that will end up hard to interpret. Could use more research

Principle: Variolation maybe good, still hard

• The problem is if you don’t want to spread it to others, you probably need to quarantine for ~a week every time you do it; but since you can’t titrate doses, the proper move is to start quite small, which means a lot of quarantining. I’d guess 5 incidents if you do a pretty good job ramping up, though with some coordination you could try different numbers as a group and more easily figure out a good dose and maybe bring this down to 2-3 incidents per person. Alternatively, you could try to test saliva or similar for action concentration.
• A main question is how much immunity delta strain confers toward future delta strain. I haven’t seen any discussion of this question—it’s probably >3x, but if it’s <2x or something (for example due to original antigenic sin), then it could be a mistake to variolate. In that world, your main move is to wait 6 months for booster vaccines

Principle: Lockdowns are pretty mentally costly

• Not expecting to see as many people means you have reduced incentives to act in socially good ways; being hampered in your life gives you lots of excuses and reduces your strength and effectiveness. I think both of these are super underappreciated and are major issues
• People’s brains are wired to have lots of human contact and start doing weird things when they don’t, including the “I’m in pain” thing that causes a variety of badnesses
• There are other effects here I’m not getting into. I know these are bounded in severity because they aren’t showing up massively in suicides or happiness, but I think they’re big and real nonetheless. I hope to write something about the strangeness of these soon, but realistically that won’t happen.

Principle: Don't pay lots of COVID-avoidance costs if you're going to almost-surely get it anyways

• I tried to make this clear to people last time, but—if you're going to be one of those people who goes to the gym maskless, just don't avoid any risks in the first place. Better yet, get it at a convenient time. But don't avoid hanging out with your friends for two months if you know you're going to get like 2 million uCOVIDs from vacation right after. (Obviously, don't spread it to your friends if they want to avoid it though.)
• If your rate is about 5k uCOVIDs for a lost hour, then it's still going to take you 200 "debates over an hour" before you have a full expected COVID. For most people, this is probably still on the side of "won't get an expected COVID in the next 6 months". However, if our Long COVID risk goes down another factor of 3 or something, many more people are going to have their risk-tolerance set such that they'll get more than an expected COVID soon anyways, at which point mathematically they should stop trying to fight it and just control their viral load and timing.

Principle: A third vaccine dose of a different type is probably fairly useful for the vulnerable

• I expect [LW · GW] the effect size is something like 3x for the vulnerable and 1.5x for others. It’s slightly higher the longer it’s been since your second shot.
• I don't know whether people should get the other mRNA vaccine (Pfizer XOR Moderna) or whether they should get something else—hopefully something we can figure out over the next week or two.

Policy summary:

(These are for individuals, not the state. I would like the state to not impose any hard rules and instead just get us more and better tests, but I know that’s a pipe dream.)

As individuals, the primary behavioral axis is still how much risky contact you have with others, and using microCOVID.org to titrate your risk level at the new rate of 1k-5k uCOVIDs per hour. However, you have some secondary options this time around. First, you can get a third dose [LW · GW] of a different vaccine (in Israel they’re already doing this); second, if you’re smart about it you can variolate yourself at less cost than before due to vaccine protection. More likely, a group of people working together could make variolation work.

On the primary behavioral axis, I think serious lockdowns are a bad idea for almost all people except the immunocompromised. I also think it wouldn't be crazy to just continue to act normal aside from reducing viral load in simple ways, and just avoid interacting with the vulnerable for a month or two until you’ve had Delta and been protected. However, I could be wrong about this and you should make your own decisions: I admit that I balk at taking a 1/200 permanent hit to productivity/vitality.

I had meant to make some more serious policy proposals for Bay Area rationalists or other groups of well-coordinated people, but I have to postpone this for a few days.

Again, remember that Delta might peak in the US in a few weeks anyways.

---

Research supported by LessWrong.

60 comments

Comments sorted by top scores.