Omicron Post #6

Previous posts: #1, #2, #3, #4, #5, last weekly post

Well, that escalated quickly. Omicron has already escalated quickly in log terms, and will soon escalate quickly in linear terms. The core questions remain the same, and we continue to continuously get better data to allow us to make better guesses and projections.

There are three central places where population-level information is available first:

  1. South Africa, because Omicron has taken over already and they have good data.
  2. Denmark, because they do all the sequencing.
  3. United Kingdom, because of S-gene-deletion data and good sequencing.

We also have a few African countries like Zimbabwe with giant spikes. But in other European countries and in the United States, the lack of sequencing makes it impossible to know how far along things are or how fast they are moving.

Thus, we must rely on what data we have, and give thanks to those who provide it.

Uncertainty abounds but there is no known link between ‘has more Omicron infections’ and ‘has ability and willingness to monitor Omicron cases’ so we should start with the assumption that Denmark and the United Kingdom are typical western countries for this, adjusted for the state of Covid-19 under Delta there relative to other places.

All of that can and should be complemented by experimentation and lab results. Alas, as per usual, challenge trials and most non-natural experiments remain illegal, so we have orders of magnitude less knowledge and certainty from these sources, and everyone is much worse off, than we could if we cared more about saving lives and making people’s lives better and actual ethics, and prioritized those considerations over ‘biomedical ethics.’ So mostly the useful findings lie elsewhere.

Here’s two charts of overall cases and positive test percentages in various places, for context. The rise in Denmark does reflect some Omicron cases, they’d still be under 1,000 on this graph without it, and the UK rise as well.

South Africa

The most hopeful news would be if South African cases peaked all of a sudden for no clear reason, the same way cases of Delta in India did, and started heading downward. We did see a blip for a few days, but was it more than a blip? My read on it is no, and there are signs of issues with data reporting to explain it.

The news on this front is still good, because it’s possible things are improving, and in the worst scenarios things should have continued to get rapidly worse. The positivity rate sticking around 30% would be actively great news.

As you can see on the graph above, the 7-day averages haven’t stopped rising, at least once Our World In Data corrected for temporary data errors. I do still find the lack of a steeper rise to be good news.

Here’s a short explanation of why it’s still too early to draw any conclusions from the death rate. Still need another week or so due to lag.

There are a bunch of threads about South Africa in the Threads section below. They basically all note that a lot of cases continue to be incidental and severity looks low, but that it’s too early to know for sure for reasons I went into on Thursday.

Here’s a video interview with Dr. Angelique Coetzee of the South African Medical Association from December 12. Most optimistic case presented so far. I want to update more but I still don’t feel like this clarifies things much.

Denmark

Denmark has the world’s best sequencing. It also has the largest number of known Omicron cases as a share of population by a lot, which is not a coincidence. And it knows cases are growing exponentially, also not a coincidence.

Here’s an update from yesterday.

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Arxiv link.

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For speed reasons I didn’t double check the math, but the principles are right and the answer is roughly correct. This is happening, and it is happening fast, and places that aren’t observing the same should still expect to be experiencing the same soon after.

Here is the official government projection from December 13:

United Kingdom

An announcement from Boris Johnson, urging everyone to get boosted and aiming to finish the job by the end of the year. Compared to the messaging I’m used to, this is quite good. The issue is not what is here, the issue is what is not here – any effort to get Omicron boosters, or any attempt to improve options for testing and treatment.

Here’s an analysis of a lagged update on the situation in the United Kingdom up through December 3.

AY.4.2 is irrelevant in the sense that it’s going to be overwhelmed by Omicron soon, but it’s also common enough and growing rapidly enough that it represents a higher previous baseline of infectiousness. It’s also relevant for looking into the future, to know that trouble of a lesser kind was already on the horizon and approaching rapidly, and starting to meaningfully impact case counts.

This is excellent and seems to have started before Omicron, which highlights how hard it is to pivot into such responses after you know you need them.

The key estimate is 0.6% for Omicron in the two weeks ending December 3, up from 0.0% before that, while remembering that December 3 is ten days ago.

We should adjust this down slightly for rapidly increasing sequencing, since Omicron cases would be sampled more from the later portion of the period, and for the choice of what to sequence not being entirely random, but these are unlikely to be large effects given the numbers involved. Let’s call it 0.5%.

How does that constrain possibility space?

Since the previous calculation was also over a two-week period, there’s a broad range of possible growth rates, which we can make work by adjusting the rate already infected on 11/21.

In the optimistic case, which also corresponds to the reports of doublings every three days, we can say 0.1% coverage already on 11/21, have a daily R0 of 1.23 (doubling every 3 days would be 1.26), and still get to about 0.5% for this period, which would have Omicron become the majority strain on Christmas Eve, minus the lag in cases from infections, so we’d have about a week. There will be a large natural adjustment in behaviors even if Boris doesn’t cancel Christmas and otherwise go around ruining life, but is a mostly vaccinated population going to lock down sufficiently hard to adjust for this kind of transmission advantage? I don’t see them doing it voluntarily, nor should they, so the question is whether one can be imposed by force and sustained.

On December 10 Guardian reports that while the government had instituted Plan B, and had noticed that Plan B would be the goggles and essentially do nothing, there remain no plans to implement Plan C. Which is good, since even if it temporarily worked Plan C is unsustainable on the timeline it would be needed, there is no sign of rushing to get Omicron boosters and/or Paxlovid to the scene fast enough to matter, and the costs of a somehow sustained Plan C that might get us that far seem clearly higher than the costs of doing nothing.

Note that the official reports (WaPo) have Omicron taking over this week, rather than next week, so why the difference? The answers here are very sensitive to exact doubling times and starting conditions, so the difference is less substantial than it might look at first glance.

Here’s some data from Scotland, from December 10, not updated yet. Direct source, dug briefly but didn’t find an updated version. Each line is one day.

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Ten days is a long time ago given how fast things are moving. That’s three or more doubling periods.

So where do we stand on this?

This is reported cases. The 21st is a Tuesday, and well before Christmas, so should have full reporting. Let’s say we can expect 750 Delta cases per million people, or about 50k Delta cases, on a weekday. So this is mostly asking if Omicron will substantially surpass Delta by then, which is approximately a coin flip between the later two categories. I’m impressed by the poll responses.

Reported first on December 13: A patient known to have Omicron in the United Kingdom has died. One death obviously means little, but zero and one are highly different numbers, and cases and deaths typically lag by three weeks, so this is disappointing news.

UK also offers this helpful report (direct link) showing Omicron with a huge household transmission advantage.

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Other Places

USA dates first known Omicron patient symptoms to November 15.

Trevor Bradford looks at data from USA and Germany and attempts to directly estimate rate of spread, building off previous thread about South Africa that was relatively optimistic about possibility things might peak relatively soon there.

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To extent we have data for the USA and Germany, this superficially looks is saying it largely matches the UK’s data, which should be our baseline assumption, but the Rt calculation comes in somewhat lower. Still very far above 1.

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Link to methodology. You can find updated figures here as per his link. At press time here are the estimates, which have gotten faster/worse:

Norway, where we earlier saw a superspreader event get noticed, is ramping up measures:

Laboratories and Experiments

Confirmation from Michael Mina that rapid antigen tests work on Omicron.

Concern that inactivated virus vaccines will fail against Omicron.

Threads

December 10 what-we-know thread from Tom Friedman, seems right but without new insight.

December 10 overview of UK government report.

December 9 summary thread from Derek Thompson, nothing new at this point. Optimistic on severity, but with appropriate caution.

December 9 thread from Andrew Lilley about severity based on South African data, no new data, cautious optimism. December 10 thread from John Burn-Murdock about the same topic, more reserved. And December 10 one from Shabir Madhi.

December 9 thread about T-cells generated from prior strains, which mostly should still work as before.

December 13 thread from Trevor Bradford noting that Omicron might not displace Delta, and it’s possible both will continue to circulate. I don’t see this as likely, but it is possible.

December 13 thread from Bloom Lab about subvariants of Omicron, and their relative levels of escape.

Prediction Markets

Here’s what’s happening at Polymarket.

Paxlovid approval by end of the year is back up to 35% based on there being a plausible schedule, and the others are interesting, but I will focus here on the Omicron ones.

Variant of High Consequence remains at 12%. Given no movement towards doing this and the month ending one day at a time, this likely should be declining faster than it has, but I thought it was a little low before. I have no problem with it now.

The Omicron-share-of-American-cases markets, are now:

1% of cases by year’s end: 93%.

10% of cases by year’s end: 77%.

50% of cases by year’s end: 20%.

These all seem low. We are going to go over 50% of cases well before year’s end in Denmark and the United Kingdom, and growth in the United States doesn’t seem that much slower. The 1% line is reflective of prediction markets not handling extreme odds well due to capital issues, this should be much higher. The 10% level also seems like it would be pretty strange if we don’t hit it, and I’d definitely buy this to at least 85% and would have my fair at least at 90%. For the 50% threshold, it’s hard for me to understand why this is an underdog at this point, given the data source is aiming to be backward-looking. I do want to give some respect to the market, but I still see this as at least 50% to happen. I wouldn’t bet against it happening at almost any price unless I had a way to hedge.

Probability Updates

Chance that Omicron has a 100% or bigger transmission advantage in practice versus Delta: 75% → 85%.

We know for a fact it has a much bigger than 100% advantage right now in the West. That includes the potentially large advantage for being new, so how confident to be here depends on the spirit of the question. But with this much escape, it seems increasingly hard for this to be wrong.

Chance that Omicron will displace Delta as most common strain: 96% → 98+%.

The graphs are very clear. This is going to happen. I will stop reporting on this one unless it goes down.

Chance that Omicron is importantly more virulent than Delta: 4% → 3%.

Chance that Omicron is importantly less virulent than Delta: 55% → 60%.

The evidence slowly adds up, but that’s mostly what one would expect. The one English death is disappointing. We won’t know much for a while.

Will the CDC label Omicron a variant of high concern before 2022? 12% → 11%.

No movement so notching this downward.

Chance we will be getting boosters modified for Omicron within 6 months of our previous booster shot: 60% → 50%.

I’m lowering this back down because of the comments that Omicron boosters might be unnecessary, and a general sense that authorities don’t care much about this happening. They might well try to pretend this isn’t necessary to avoid a mess of some kind.

Chance we are broadly looking at a future crisis situation with widely overwhelmed American hospitals, new large American lockdowns and things like that: 25% → 25%.

I need to game this out more to get a better idea of what would trigger this kind of response, regardless of whether anyone wants to do it or has any intention of doing it before the crisis happens. So I notice I’m not confident in this estimate but I don’t have a better one.

Will Omicron be >1% of all cases by the end of the year? 94% → 97%+.

The timing seems like it’s baked in and this may well have already happened. I’m putting on a plus to indicate that I’m including model error and cowardice a bit in not going higher, which means I’d never accept a bet against this happening at anything like these odds.

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32 Responses to Omicron Post #6

  1. A1987dM says:

    So 45% chance that the number of people in US to have received at least one dose by Jan 1 will be within 0.4% of 247 million? Am I missing something?

  2. Janko says:

    Hey Zvi, given that the omicron infection seems unavoidable, I intend to quickly arrange access to Paxlovid for me and my close family (we’re based in Eastern Europe). At the same time, I’m afraid it might be difficult to do so legally, and I’m having some reservations with regard to taking a novel drug with unknown long-term effects, tested in one study by Pfizer. Thoughts?

    • Humphrey Appleby says:

      How afraid do you need to be of COVID? If you are reasonably young, healthy, and vaccinated, then the risks of a COVID infection are known, and are exceedingly low (similar order to risks from flu). Sure you can reduce them further by taking Paxlovid, but you are talking further reduction of pretty minuscule risks. Meanwhile, the risks of Paxlovid are unknown, and I would be inclined to say it is not worth it.

      If you (or some family members) are high risk for COVID, it could be a different calculus.

    • Nicholas says:

      Is it even possible to acquire Paxlovid anywhere currently? I was unaware that it was being sold yet anywhere in the world.

    • TheZvi says:

      If you can indeed get Paxlovid access, and you get covid, yes obviously you take it.

      • Humphrey Appleby says:

        Zvi: why? Lets say, for the sake or argument, that you are in your 20s, healthy, and vaccinated. The residual risk from COVID is very well quantified by now, and is utterly minuscule. Meanwhile, there are unknown unknowns associated with Paxlovid – side effects, long term safety etc – on which there is still a great deal of Knightian uncertainty. How could the minuscule risk of COVID possibly justify rolling the dice on unknown unknowns associated with Paxlovid?

    • Mr. AC says:

      On balance your calculation might be different, but I’d stick with Fluvoxamine for now. Much easier to acquire, used A LOT so side-effects very well known, see https://astralcodexten.substack.com/p/higlights-from-the-comments-on-ivermectin#:~:text=giving%20you%20a-,fluvoxamine%20,-prescription%20if%20you're .

  3. Martin says:

    https://twitter.com/pavitrarc/status/1470447735585214464 says 29 out of 217 samples with collection date 12/8 were SGTF, in Seattle.

  4. Seb says:

    Here in Ontario our public health folks are saying that 15% of confirmed cases today are omicron, and it will be dominant within a few days. I can’t imagine the rest of Canada will be too far behind us.

  5. Alex says:

    Is the link title “ Concern that inactivated virus vaccines will fail against Omicron.” misleading or did I misunderstand it?

    The thread says that (1) Pfizer & AZ are worse against Omicron and (2) inactivated virus vaccines are worse generally, thus worry. But there is no actual information there, and weren’t inactivated vaccines supposed to be better against variants in general?

    (The rest of the thread talks about production which is fair, but that’s not relevant to the vaccines failing question.)

    • TheZvi says:

      So I think this is generally fair, in the sense that vaccines can be abstracted as working by producing some level of antibodies, and Delta->Omicron divides that score by some constant, thus making Pfizer/AZ worse, but if the inactivated ones were already behind AZ, it’s logical to guess that they now are likely to have very little effectiveness, at least against infection, at all.

  6. bro says:

    Your link for “Concern that inactivated virus vaccines will fail against Omicron” (https://twitter.com/HelenBranswell/status/1469709919746199552) does not substantially support that.

    It’s primary concern is that inactivated virus vaccines will be harder to update due to specifics of their manufacturing process.

    The only info in there other than that manufacturing detail is very old and well-integrated idea that Sinovac has been generally less effective.

    • bro says:

      Like there’s nothing specificallly in there that provides any insight into “concern that inactivated virus vaccines will fail against Omicron” that goes any deeper than “we’ve seen that inactivated virus vaccines have been less effective generally”

    • dude says:

      Like there’s nothing specificallly in there that provides any insight into “concern that inactivated virus vaccines will fail against Omicron” that goes any deeper than “we’ve seen that inactivated virus vaccines have been less effective generally”

    • TheZvi says:

      I note my logic in the thread above. Agree on reflection it wasn’t a great link but I do buy the worry.

  7. fella says:

    Also you keep calling “Trevor Bedford” “Trevor Bradford” lol https://www.google.com/search?q=site%3Athezvi.wordpress.com+%22trevor+bradford%22

  8. Steve Price says:

    University of Washington reports on 12/8 that 29 of their 217 covid sequences for the day were Omicron.

    Pavitra Roychoudhury
    @pavitrarc
    ·
    12h
    Replying to
    @trvrb
    and
    @UWVirology
    Yes, 29 out of 217 samples with collection date 12/8 were SGTF.
    Breakdown by collection date:
    11/29/21: 2/357
    11/30/21: 1/243
    12/1/21:1/169
    12/6/21:7/255
    12/7/21:11/168
    12/8/21:29/217
    Trevor Bedford
    @trvrb
    ·
    12h
    Wow. I was somehow hoping we’d not be here by now. Really important data. Thank you so much for sharing and the entire team for the tireless testing effort.

  9. Pingback: Omicron in China - Marginal REVOLUTION

  10. Pingback: Omicron in China – Marginal REVOLUTION – NewsDesk

  11. Pingback: Omicron in China – Marginal REVOLUTION - cryptomarket24news.com

  12. It's over says:

    Omicron infection is practically unavoidable (BRN=10-12?) in the next 3 months, Pfizer vaccine is only ~33% effective (per Discovery Health), vulnerable groups are even less protected, omicron boosters will be available no sooner than in ~May 2022, Paxlovid is an inaccessible new drug tested only in one study conducted by a pharmaceutical corporation with a questionable reputation. We don’t know much about the omicron long Covid and its other long-term effects.

    Prices increase, people lose jobs, tensions rise, governments become increasingly totalitarian, mental health plummets, environmental pollutants destroy our health and fertility, fertility rates among “gifted/privileged” groups are low, tribal and culture war tensions make people suffer in isolation, and I have an impression that the synergistic effects between these and dozen other factors will set up a dystopia for the next years.

    Time to fall into a spiraling depression SSRIs & CBT won’t help with? :(

    • Dave says:

      Those vaccine numbers are indeed a bit depressing. 30% fewer severe cases plus 23% less vaccine protection against severe cases works out to a bad deal on the whole.

      Hopefully there is an error in these numbers, like perhaps vaccine protection is being measured relative to the general population which includes a lot of people with natural immunity. (To illustrate: if 100% of people had natural antibodies, measured vaccine effectiveness in that population would be close to zero. There is a lot of natural immunity in S Africa now.)

      • lunashields says:

        My guess is that significant majority of people who’d die from covid already died. Not that much dry tinder is left. Same for severe cases.

  13. CyTex says:

    Per the City of Houston (Texas) SARS-CoV-2 Wastewater Monitoring Dashboard:
    Nov-19 0 of 39 treatments plants detected Omicron
    Nov-26 8 of 39 treatment plants detected Omicron (first detections in the area)
    Dec-6 25 of 39 treatment plants detected Omicron

  14. boudoir says:

    When you posted this,
    “Will at least 50% of U.S. COVID-19 cases be from the Omicron variant on January 1, 2022?”
    was at 20% Yes.
    Now it’s at 75% Yes.
    https://polymarket.com/market/will-at-least-50-of-us-covid-19-cases-be-from-the-omicron-variant-on-january-1-2022

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