Covid 12/17: The First Dose
The Pfizer vaccine is being deployed to health care workers and long-term care facility residents. The Moderna vaccine is close behind, with the full FDA report already out. There were some small extra delays thrown in for good measure, on the order of a few days, that doubtless killed a few people but shouldn’t delay the overall path of events. We are now in the vaccination stage of the pandemic. If the trial results are to be believed in detail, by the end of next week those getting the first dose will largely already be immune, and the population immunity effects can begin to compound and help turn the tide. They will start out small, but soon start growing faster, and every little bit helps.
There even seems to be a good chance that overall new infections would have already peaked if not for worries about Christmas and New Year’s coming up soon. Positive test percentages seem to be starting to even out or slowly decline as we get clear of Thanksgiving, and death rates are not rising as much as they would be rising in the scenario where data snags and testing issues were the only reason we didn’t notice things getting even worse than they are. If anything, death rates suggest a better picture than the positive test counts.
In other great news, Over the counter $30 Covid-19 test approved by FDA. It’s official. Woo-hoo! Three million over the counter tests this month, then they ramp up production. We could have done this a long time ago and solved the whole pandemic, and instead it’s going to be a drop in the bucket that shows up late to the party, but every little bit helps.
Alas, as always, none of that changes the short term situation much. There’s lots of Covid-19 out there, and if anything there are even more reasons to play it safe right now. Large Christmas gatherings or New Year’s parties are a profoundly bad idea.
In many ways, it seemed like this week was mostly ‘cut to one week later’ with few if any surprises, except for the approval of the first at-home Covid-19 test.
Let’s do the numbers.
As a bonus, here is someone else running their version of the numbers on a state level. He does this monthly, and they’re useful graphs with solid commentary. It’s a generally good newsletter.
(Technical note: Brief uncredited screenshots whose source isn’t obvious are from CNBC live update page or CNN live update page. I’m experimenting with this as a quick way to get sourced info across, let me know if you think it’s a good idea to keep doing this.)
The Numbers
Predictions
We got a peak. Test count and deaths were close, the positive rate went small down instead of small up.
Last week’s prediction: I predicted a 14.3% positive rate on 11 million tests, and an average of 2,550 deaths per day.
Results: We got a 13.5% positive rate on 10.95 million tests, and an average of 2,617 deaths per day.
Prediction: 13.1% positive rate on 11.5 million tests, and an average of 2,850 deaths per day.
Deaths
I interpret this as a backlog of deaths from previous weeks showing up in the Dec 3-Dec 9 reporting in the Midwest and South, with the numbers we see this week being about where the real death rates are once again, and things still getting worse everywhere given the lag. The Northeast and West numbers came in a little higher than I expected, which cancelled out, but nothing here seems too surprising. Peaks outside of the Midwest are likely still at least a few weeks away, but I do not expect things to get that much worse than they are now before they turn around.
Positive Tests
Seems clear the Northeast got ahead of itself last week and that has now been smoothed out but is still getting worse, the Midwest has peaked, and the West and South are in trouble. As usual, I rely more on the test percentages
Test Counts
Positive Test Percentages
I’m ready to believe the Midwest is headed in the right direction. I am not ready to believe the Northeast is following suit quite yet. That seems much more likely to be a blip and nothing more, although the snowstorm outside my window at the moment might slow things down a bit - being forced inside is not great but no one leaving the house at all is actively useful. Thus I think the baseline scenario is that the Midwest continues to drop. The South is the opposite case, with this number coming in a bit ‘too high’ so I expect it to level off a bit next week despite the true number of infections likely still rising a bit.
It is worth noting that California is now at 11.9% positive tests. The attempts to lock things down aren’t working, presumably because they are not locking things down due to being sick of it all, and also because they’re going after the wrong things too harshly with no end date in sight, and forcing people into all-or-nothing choices. That’s also despite weather that shouldn’t create as big a winter crisis as other areas. The counter-argument is that things might have been about to go the way of Arizona (32%), Colorado (28%), Idaho (47%) or Nevada (40%), but Oregon (5%) and Washington (8%) seem like better parallels and thus a strong counter-argument to that.
Covid Machine Learning Projections
Predicted total infected 17.9% on December 2, 634k new infections per day.
Remember, those numbers are several weeks behind, and in general I consider them to be soft lower bounds.
Europe
America now has twice as many infections as any of the European nations tracked here. Germany and the United Kingdom once again seeing more infections. Italy rapidly improved on that front but is still seeing a lot of deaths due to lag. The European strategies seem to continue to oscillate between being harsh to get things under control, and at other times letting things get worse. This does not seem obviously worse or better than the de facto American strategy of doing nothing.
All I Want For Christmas is a Covid Vaccine
It seems all it took to get the FDA to approve the vaccine on Friday, only one day’s worth of deaths after their panel had taken its sweet time to meet and give its seal of approval, was for Mike Meadows to tell the head of the FDA to resign if they didn’t give approval by the end of the day. It seems things were being held up because they had not prepared a proper “fact sheet” for the vaccine, which prompted Alex Tabarrok to calmly suggest maybe getting that done in advance next time.
The FDA denies that the pressure impacted their timetable:
He has to say that, because of the mindset ‘this was either due to science or due to pressure’ rather than the pressure being used to get around stupid red tape after the scientific job was already done (including lots of other stupid red tape), and also to save face. I am very confident he is lying here.
Calling for the head of the FDA if he doesn’t find a way to assemble a fact sheet by end of business is exactly the type of thing one does when giving such questions the urgency they deserve. We still didn’t vaccinate people until Monday, but things could have slipped even further. It’s also worth noting that the vaccine didn’t begin shipping until after every prior step was completed, which caused an additional unnecessary delay.
Early vaccinations seem to be running into some snags. Here’s a report from Florida. Hospitals are getting lots of doses, yet only using a few percent of them each day. That does not seem like the right sense of urgency. It also says that due to production concerns future shipments are on hold, which is a lot scarier. I haven’t seen other indications of things being on hold, but that would be very bad news.
Other shipments seem to have issues with being... too cold? Not sure exactly what goes wrong when that happens.
Credit where credit is due: Looks like Moderna is being allowed to submit with 7-week instead of 8-week safety data, and without full verifications (source):
Once again, it’s all minor in the grand scheme, provided this did not slow down production or vaccination.
What matters is the long term path. That seems to still mostly be on track for early spring. We just bought another 100 million doses of the Moderna vaccine. By waiting, we gave ourselves the chance to save a tiny bit of money, and in exchange we slowed getting back to normal by a month. Not maxing out vaccine purchases was a supremely costly decision in terms of expected lives lost and lives ruined. I originally wrote it was a “mistake,” but on reflection that implies things about decision makers that I don’t endorse. Not a mistake.
Well, you should know this already, but FDA Delenda Est:
The full FDA report on the Moderna vaccine is here.
Also, um, have you seen the one-dose efficacy data because, I mean, holy shit:
Guess who said the Pfizer vaccine was safe and effective after one dose? Yep. The FDA.
In what world is giving the second dose to the same person, raising them from 87% to 96% protected, a higher priority than vaccinating a second person?
Guess who is the Only One Man brave enough to step up for this obviously correct strategy? Who is the most ridiculed of them all? It is, of course, the quintessential Florida Man, Governor DeSantis. Remember when DeSantis was history’s greatest villain for not closing beaches while Andrew Cuomo was a hero despite literally forcing nursing homes to take in people who were Covid-positive? Huh.
I do want to note the counterargument to this, which is that if an individual is 86% protected they have to decide whether to resume normal life while waiting for their second shot, whereas at 95% anyone not at high risk can safely take a lot more risk. At a societal level, of course, this if anything backfires further, but at the individual level there are definitely gains to concentrating your immunity.
You know what would be another way to get more people vaccinated? Use our entire supply of the vaccines! As in, the bottles provided are so overfilled that pharmacists can extract one or sometimes even two extra doses out of each five-dose vial. That is quite a bit of extra vaccine going to waste by default! Which is fine for a vaccine or other medicine with abundant supply, where avoiding contamination and ensuring a buffer against spillage or other surprises is important, but is totally not fine here. Luckily for us, the FDA has decided to declare using these extra doses “acceptable,” although as of the article’s publication that guidance was not yet official, opening the door for the extra doses to be used.
There’s still this, though:
Both Pfizer and FDA said that leftover vaccine from multiple vials should not be mixed, because of the contamination risk.
To which I would like to reply, that’s an interesting answer, can you please show your work?
It seems to imply strongly that the risk of contamination for any given injection is sufficiently high that multiplying that risk by two or three makes it net negative to administer the vaccine. That would mean it is eating up a large fraction of the gains from vaccination, as opposed to us essentially never hearing about contamination issues.
If we presume that a vial right now has a random amount of leftover vaccine, then by default the average vial should have about half a dose remaining after administering all full doses. That means that if we average six doses otherwise, we can expand supply by another 8% or so by combining those doses, or 6% or so if we are willing to combine up to two vials but not three. We are throwing that away because it would increase “risk of contamination” and again I very much want to see their work.
I love this gem:
I will gladly accept this particular demand for subgroup analysis if it keeps us from utterly wasting vaccinations on people who already have the immune response the vaccine is designed to create. Even if the vaccine was 100% effective in this group with zero side effects, that’s obviously hugely wasteful. Yet it looks like hospitals are mandating that such people get vaccinated anyway.
How fast could we have gone? Remember how we learned last week how the Moderna vaccine was designed in two days? I was surprised by that because my father said he could have done it in one, and it looks like Pfizer agrees with his timetable.
COVID-19 Vaccine Allocation Dashboard by Benjamin Renton tells us where America’s vaccine doses are headed. The first shipment seems to be allocated by population, as expected, but later in December the numbers quickly diverge, and it’s not obvious what is driving this. There isn’t an obvious political economy story here, and one could plausibly credit a lot of the differences to shipments not having been catalogued yet. It seems like consistently 6-7% or so of the population is getting vaccinated in the places that are getting the most, and there are a lot of ‘null’ entries here, so the hope is that this represents roughly a 6.5% of population vaccination distributed smoothly by the end of December. That would match previously announced quantities. If we did get that, then combining it with growing immunity from other sources, the tide should turn rapidly in January, unless sufficient additional control systems set in to un-turn it.
In other vaccine news around the world, The Oxford/AstraZeneca Vaccine Efficacy Data is in. The whole process seems to have been quite the royal mess, making it hard to be at all confident in the efficacy numbers. The standard Very Serious Person response is to re-run the trials, including checking to see if the mistaken half-dose given in the UK was a random stroke of genius. There does seem to be a plausible theory of how that might be true. My guess is that efficacy is something like 75%, in between the two trial results, and the half-dose makes only a small difference either way, but given we have limited vaccine supply I’d definitely go with the initial half dose for now.
The big (alas mostly rhetorical) question remains, why haven’t we approved this vaccine? The safety data seems very solid and I still can’t believe people continue to fret about a single person out of tens of thousands getting sick with something, anything despite not even having a mechanistic story of how the vaccine could be related, let alone it happening often enough for us to want to care. Our confidence interval for effectiveness should presumably be something like at least 50% effective and at most 90% effective, and if it’s 50% effective then we should get on this yesterday, obviously. Which we of course will not do.
Similarly, I was reminded this week that many arab countries have approved the Chinese vaccine, and was asked why this is so. I replied this was so because it probably works. There is no mystery to explain.
Perhaps we should consider trading vaccines with the Russians? Their consumer watchdog is asking those who get vaccinated to refrain from alcohol for two months, as Russians, in Russia, during the winter. I totally get how this can help build up immunity but come on. This is what one calls ‘not going to happen in a million years.’ Bring them vodka or bring them death, and if it’s both or neither for arbitrary values of vodka and relatively low levels of death, I’m pretty sure we already know their revealed preference.
My guess, of course, is that the watchdog is trying to use this as an excuse to get Russians to drink less, with the breakdown between ‘Russians drink way way too much and it’s worse for them than Covid-19 so getting them to cut down by any means is important’ and ‘Very Serious Person gets to take away only joy in people’s lives and is not about to miss that opportunity’ left as an exercise to the reader. Some actions are overdetermined.
I, on the other hand, have not had a drink of alcohol in years. May I suggest free trade?
They’re also experimenting with combining the Sputnik vaccine with the one from AstraZeneca. Given the issues with the first dose building up immunity to the vector needed for the second dose, it makes sense that mixing and matching could be good. I’m glad they are trying this. However, this also points out the obvious, which is that combining vaccines is on priors more effective than only doing one, and if that’s true and the safety data is in, why are we not taking all of the vaccines?
Sanofi vaccine given in insufficient doses in Phase I/II trials, and only generated what confidently looks like sufficient response in 18-49 year olds. Here’s a less detailed news report that also mentions delays in another vaccine. So they’re going to redo the studies, and while doing so they will not be doing a Phase III on 18-49 year olds, even though there are plenty of other vaccines that can serve the older cohort while we give Sanofi’s vaccine to the young. On top of that, they tested a lower dose and it seemed to work in the young, so that lets us get more people vaccinated faster! Perhaps we should be going a step further, and considering that maybe younger people need smaller doses of other vaccines as well. That would be another way to get this done faster. Not that anyone will ever give any of that the slightest consideration.
I do genuinely feel for regulators sometimes. Even when they want to do the right thing, they face horrible incentives, blamed only for individual bad things that result from the things they do, without getting credit for anything good or being blamed in any meaningful way for holding things up. Consider this throwing under the bus of India’s regulatory authority. It spends most of its time blaming them for approving things improperly, or letting trials happen that had individual adverse events. You see, these things ‘undermine confidence.’ It does not mention, at all, failure to run challenge trials or use other methods, including simply ‘run more and bigger trials sooner’ to get results faster, or its failure to actually do the job of ensuring the manufacturing of its full capacity of 3 billion doses per year of vaccine.
Everything Matters Versus Nothing Matters
A paper, phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events, studies several such events. In particular, it seems that one conference held in Boston was responsible for a large percentage of all Covid-19 cases in the area for months afterwards, and subsequently for almost 2% of nationwide cases if you count all cases that derive from a virus variation that originated at the conference. That sounds like a really terrible conference.
The catch is that, like everything else in this pandemic, all those cases are intertwined with the control system. The counterfactual where the conference was cancelled does not contain 2% fewer Covid-19 infections or 2% fewer deaths. As people notice the extra infections, they adjust their behaviors, and governments adjust their rules. If you assume only fully naive SIR-model-style immunity effects from only detected cases, by now immunity has reduced new infections by 58%. If you started off 2% higher, those effects start off 2% stronger, and a majority of the increase cancels out. Then adjust that for the infections we miss, and the selection effects of who gets infected, and combine with the other aspects of the control system.
These are the two pandemic perspectives. On the one hand, every new infection permanently increases the infection rate, which then moves exponentially, so the conference is responsible for 2% of infections. On the other hand, control systems, so it’s not clear that the conference had a meaningful overall long term impact at all. In the extreme, if the control system was always destined to break down in November as the weather got colder, making things worse earlier can potentially build up immunity earlier, which prevents hospital overload and gives us a smaller peak number of infections, which minimizes overshooting after the corner gets turned and gets people overall better treatment. So being careless is either deeply irresponsible, actively saving lives, or something in between. Life is confusing like that.
Further Research Is Needed
Fast Grants and Marginal Revolution provide suggestive early results that fluvoxamine, and perhaps SSRIs and sigma-1 receptors more broadly, could provide an effective treatment for Covid-19. Given robust safety records, these do look promising, with the downside that fluvoxamine is reported to be difficult to quit. This is the kind of thing we would have known in April if we had our act together. Instead, even if these treatments work, we won’t be confident enough to use these treatments widely until most deaths have already happened. The sample and effect sizes here are quite small, so it could easily go either way.
You Should Know This Already (Inessential Reminders)
Yes, Moderna’s vaccine prevents transmission. One dose is good for reducing infection by 63%, two by over 90%.
CDC Delenda Est:
Our government is still hard at work slowing down the vaccination process:
As a reminder, if you only give someone one dose, nothing bad happens, and you can give out the second dose later with full benefits therefrom. This large of a reserve only has one purpose.
Reddit is asked: why is there an explicit line between Phase 3 and roll out of a vaccine? The responses point to bureaucratic, regulatory and “ethical” justifications aplenty, most of which readers will already be familiar with. Under normal circumstances they would even make sense.
More confirmation of what is important to “bioethics.”
Here’s another confirmation that what scares such people most is that things of value might be allocated to those who value them most, as measured by their willingness to pay, or who might go on to produce the most value. You see, it’s a scandal and tragedy when we prioritize treating the President of the United States over more ‘ethically deserving’ others, and we have to watch out before we allocate resources where they might be useful. If we’re not careful, next thing you know we’ll have an entire economy full of producing useful things and allocating them where they are valued most and can produce the most value. That would be the worst.
Household gatherings are driving a lot of the spread, but contact tracing works if and only if there are contacts one can easily trace, and assumes that the contact was the source. It’s still worth doing, and still provides useful information. But one must be careful with interpretation:
T
Thus, Nate and Patrick make strong points here, but it is even worse than the initial impression. Even if one has a contact that tests positive, and the timeline works out that they could have infected you, that doesn’t mean that was the source of your infection. Thus, it’s not that 74% of known sources come from households and social gatherings, and then some cases have no known source. It’s that of the cases where there is a known source, 74% of those involve households and social gatherings, but we don’t know how often that is actually the source.
I do think it’s right that social gatherings and exposure within households are the largest source of cases, and likely the majority of them, but the data we have is not sufficient to reach such conclusions.
Here is an analysis of why the west failed so utterly at contact tracing and other places succeeded. This all seems simple. Most nations did not attempt (the word ‘try’ is so overloaded I’m going to mostly taboo it) contact tracing. At maximum, they attempted to take symbolic action that they could cite as an attempt to do contact tracing. Between privacy concerns, distrust of government, and a complete unwillingness to ever compel anyone to go anywhere, do anything or reveal any information unless they’ve been arrested for a crime, or to spend money on things like getting people places to safely and comfortably quarantine even when they wanted to do so, and fearing (I think correctly) that if they did any of that people would not get tested and otherwise go crazy, they settled for symbolic action. There was not even an attempt to scale up to numbers of tracers that might plausibly have been adequate. Then case numbers quickly got out of hand, and one thing the places that succeeded via contact tracing had in common is they did so early, before things got out of hand.
So we did nothing, while Vietnam did this (source that includes more):
There’s also this inessential lighter side twitter video link about the joys of contact tracing. I was amused.
Non-essentially, more restating “ethical” and otherwise nonsensical reasons why we should not do the things we obviously should do, via MR. Not doing these things has caused and will cause many, many people to die, and many lives to be destroyed, and all of us to be dramatically worse off.
Should kids get snow days off during remote learning? New York City mayor DeBlasio, owner of a true zero percent approval rating, has picked the side you would expect, saying ‘snow days are over.’ He’s also saying New York should prepare for a ‘total shutdown’ after Christmas.’ Joy is the enemy and must everywhere be destroyed.
Should those instructed at home get snow days? Depends on what snow days are, and what schools are. Rather than restate my views I’ll let everyone ponder on their own.
Or, if you don’t know the following particular thing already, then we need to fix that, because the WHO says so:
Many platforms have a principle that if you disagree with the WHO or CDC (also known as ‘the lying liars who said masks don’t work and have similarly only admitted fact after fact months after they had become clear’) that your posts and videos will be taken down. Wordpress does not have such a principle, so I should be safe here, but if I did not have LessWrong as an automatic backup (and my drafts saved in Google as a second backup) I would be sure to stash additional copies. If I was posting this content to places like YouTube, Facebook or Medium, my expectation is that at least some posts would have been taken down.
Even the Internet Archive does not seem reliable, as they have announced plans to begin putting warnings on past content rather than offer up the web purely as it was. That pretty much signals that at some point, perhaps reasonably soon, they will start taking down records of things that powerful people sufficiently dislike.
Like most modern rules, this rule is not reliably and fairly enforced. If it was, it would be obvious that the rule was absurd and unacceptable. Instead, the rule is that when people are inclined to take something down, it is considered a valid excuse to cite disagreement with official sources, despite the known unreliability of those official sources.
If you tell people they aren’t allowed to go to the office, they’ll find offices where they may, such as in the quiet cars of the Long Island Railroad.
When you don’t let people get treatment until they prove they are sick enough for it, at which point the treatment is being given too late, you end up not using it:
In Other News
Russian Doll is in fact excellent. Thought experiment: If this happened to you, other than making a killing in various markets, what would you do? Would you be able to stop the pandemic?
Non-Covid: FDA also approves genetically modifying pigs. They don’t fly.
FDA panel member explains her vote against approval of Pfizer vaccine, potentially ‘undermining confidence,’ because the panel recommended it be given to 16-17 year olds in addition to those over 18, without having enough specific evidence for that, and the panel member fully supporting vaccinations in those over 18, and the obvious fact that no one under 18 is going to get a vaccination for a long time either way.
FAA generously decides to not attempt to murder its pilots at this time:
In welcome news, Pelosi denounces all her policy positions:
Carbone, which pre-pandemic was the only restaurant in New York that I both wanted to dine in and couldn’t get a table at when I wanted one, is taking outdoor dining to the next level. That next level appears to be ‘indoor dining,’ which they are claiming does not technically count so long as the ground it is built upon is legally a sidewalk.
Germany confirms they are engaging in triage (in German).
If you don’t need to be quarantined, you can have your own line at the airport.
Skin in the game:
San Mateo County in the San Francisco area declines to Sacrifice to the Gods and shut everything down in ways known to not be effective, explains its reasoning in detail.
Not that anyone should expect people to obey the new California lockdowns, which is one reason why they definitely won’t work (source):
In a cool little piece rounding up views on techno-optimism, we get this perspective:
It is obviously correct that given the restrictions placed upon us, the disruptions we suffered in 2020 would be a drop in the bucket compared to attempting similar restrictions in the year 2000 for a similar length of time. Mobile and internet technology has proven its value many times over.
But that doesn’t mean we would have had worse outcomes! It seems highly plausible we would have had much better outcomes on at least some fronts.
On the economic front, we would have had to choose either to actually suppress the virus, in which case we get much better outcomes all around, or to accept that the virus couldn’t be stopped, which also produces better economic outcomes.
Our technological advancement gave us the choice to make massively larger Sacrifices to the Gods rather than deal with the situation. And as we all know, choices are bad. We also are, in my model, much more inclined to make such sacrifices now than we were in the past, even when the trade-offs are similar, which ties into my view that simulacra and maze levels are higher, with a larger role played by fear of motive ambiguity. We might have been willing to do challenge trials or other actual experiments, and have had a much better handle on things quicker on many levels.
Here’s a quote from Tyler Cowen yesterday that illustrates the issue quite well, while also showing how much else we have lost:
Here is my earlier Bloomberg column rejecting the notion of forced quarantine of individuals for Covid-19, mostly on rights grounds, though I add some consequentialist arguments. I would not trade in the American performance for the Chinese anti-Covid performance if it meant we had to weld people inside their apartments without due process, for instance, as the Chinese (and Vietnamese and others) did regularly.
Seriously, what the hell, hero? You wouldn’t make that trade, in hindsight, knowing that their method would work and our method would be this awful?
I think not making this trade, under these conditions of assured outcomes for both choices, and given only these choices, is utterly completely insane.
The civilization that chooses thus, does not survive long.
It is an open question whether being forced to give up on containment entirely, and accepting a lot of deaths, would have been a better outcome than over a year of Covid lockdowns of varying severity that we got instead. One could make a reasonable case for both sides even in hindsight.
But to outright say, no, we’d rather fail than use the means that work because we might do things without “due process”? Did you see anyone using “due process” this whole time for anything other than regulatory interference with those trying to solve the problem? I didn’t. I saw a bunch of fiat restrictions of freedom with no legislative backing that were much bigger and didn’t work, instead of restrictions that in total were much smaller and did work, together with lots of restrictions on doing anything useful.
One thing we definitely wouldn’t have had in the year 2000 would be mRNA vaccines.
It is good to be reminded that the vaccine effort was extraordinarily fast, innovative, safe and effective. That doesn’t cancel out the fact that it could have been much faster and much more effective if the people saying it couldn’t be done had interfered less with the people doing it. And while that interference was a huge problem, the interference with other things like testing (or masks, or things as simple as ordinary life) was far worse.
Both are important. And there is a very optimistic take that combines both. If we did all of this despite the best efforts of many of the most powerful people and organizations and dynamics, then imagine what we could do if we took those gloves off!
I am not expecting this outcome, but we should keep shouting it from the rooftops, as soon as we are done shouting for one-dose vaccinations. If we can use the pandemic as an impetus to move from telling people it cannot be done and they are not allowed to do it, for most worthwhile new values of it, to providing subsidies or even giving people the freedom to act at all, across a variety of other domains, than perhaps the whole of 2020 will have been worthwhile after all.