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Book Review: Andy Slavitt’s Preventable

Like Michael Lewis’s The Premonition which I reviewed earlier, Andy Slavitt’s Preventable is a story of heroes, only all the heroes are named Andy Slavitt. It begins, as all such stories do, with an urgent call from the White House…the President needs you now! When not reminding us (e.g. xv, 14, 105, 112, 133, 242, 249) of how he did “nearly the impossible” and saved Obamacare he tells us how grateful other people were for his wise counsel, e.g. “Jared Kushner’s name again flashed on my phone. I picked up, and he was polite and appreciative of my past help.” (p.113), “John Doer was right to challenge me to make my concerns known publicly. Hundreds of thousands of people were following my tweets…” (p. 55)

Slavitt deserves praise for his work during the pandemic so I shouldn’t be so churlish but Preventable is shallow and politicized and it rubbed me the wrong way. Instead of an “inside account” we get little more than a day-by-day account familiar to anyone who lived through the last year and half. Slavitt rarely departs from the standard narrative.

Trump, of course, comes in for plenty of criticism for his mishandling of the crisis. Perhaps the most telling episode was when an infected Trump demanded a publicity jaunt in a hermetically sealed car with Secret Service personnel. Trump didn’t care enough to protect those who protected him. No surprise he didn’t protect us.

The standard narrative, however, leads Slavitt to make blanket assertions—the kind that everyone of a certain type knows to be true–but in fact are false. He writes, for example:

In comparison to most of these other countries, the American public was impatient, untrusting, and unaccustomed to sacrificing individual rights for the public good. (p. 65)

Data from the Oxford Coronavirus Government Response Tracker (OxCGRT) show that the US “sacrifice” as measured by the stringency of the COVID policy response–school closures; workplace closures; restrictions on public gatherings; restrictions on internal movements; mask requirements; testing requirements and so forth–was well within the European and Canadian average.

The pandemic and the lockdowns split Americans from their friends and families. Birthdays, anniversaries, even funerals were relegated to Zoom. Jobs and businesses were lost in the millions. Children couldn’t see their friends or even play in the park. Churches and bars were shuttered. Music was silenced. Americans sacrificed plenty.

Some of Slavitt’s assertions are absurd.

The U.S. response to the pandemic differed from the response in other parts of the world largely in the degree to which the government was reluctant to interfere with our system of laissez-faire capitalism…

Laissez-faire capitalism??! Political hyperbole paired with lazy writing. It would be laughable except for the fact that such hyperbole biases our thinking. If you read Slavitt uncritically you’d assume–as Slavitt does–that when the pandemic hit, US workers were cast aside to fend for themselves. In fact, the US fiscal response to the pandemic was among the largest and most generous in the world. An unemployed minimum wage worker in the United States, for example, was paid a much larger share of their income during the pandemic than a similar worker in Canada, France, or Germany (and no, that wasn’t because the US replacement rate was low to begin with.)

This is not to deny that low-wage workers bore a larger brunt of the pandemic than high-wage workers, many of whom could work from home. Slavitt implies, however, that this was a “room-service pandemic” in which the high-wage workers demanded a reopening of the economy at the expense of low-wage workers. As far as the data indicate, however, the big divisions of opinion were political and tribal not by income per se. The Washington Post, for example, concluded:

There was no significant difference in the percentage of people who said social distancing measures were worth the cost between those who’d seen no economic impact and those who said the impacts were a major problem for their households. Both groups broadly support the measures.

Perhaps because Slavitt believes his own hyperbole about a laissez-faire economy he can’t quite bring himself to say that Operation Warp Speed, a big government program of early investment to accelerate vaccines, was a tremendous success. Instead he winds up complaining that “even with $1 billion worth of funding for research and development, Moderna ended up selling its vaccine at about twice the cost of an influenza vaccine.” (p. 190). Can you believe it? A life-saving, economy-boosting, pandemic ending, incredibly-cheap vaccine, cost twice as much as the flu vaccine! The horror.

Slavitt’s narrative lines up “scientific experts” against “deniers, fauxers, and herders” with the scientific experts united on the pro-lockdown side. Let’s consider. In Europe one country above all others followed the Slavitt ideal of an expert-led pandemic response. A country where the public health authority was free from interference from politicians. A country where the public had tremendous trust in the state. A country where the public were committed to collective solidarity and the public welfare. That country, of course, was Sweden. Yet in Sweden the highly regarded Public Health Agency, led by state epidemiologist Anders Tegnell, an expert in infectious diseases who had directed Sweden’s response to the swine flu epidemic, opposed lockdowns, travel restrictions, and the general use of masks.

Moreover, the Public Health Agency of Sweden and Tegnell weren’t a bizarre anomaly, anti-lockdown was probably the dominant expert position prior to COVID. In a 2006 review of pandemic policy, for example, four highly-regarded experts argued:

It is difficult to identify circumstances in the past half-century when large-scale quarantine has been effectively used in the control of any disease. The negative consequences of large-scale quarantine are so extreme (forced confinement of sick people with the well; complete restriction of movement of large populations; difficulty in getting critical supplies, medicines, and food to people inside the quarantine zone) that this mitigation measure should be eliminated from serious consideration.

Travel restrictions, such as closing airports and screening travelers at borders, have historically been ineffective.

….a policy calling for communitywide cancellation of public events seems inadvisable.

The authors included Thomas V. Inglesby, the Director of the Johns Hopkins Center for Health Security, one of the most highly respected centers for infectious diseases in the world, and D.A. Henderson, the legendary epidemiologist widely credited with eliminating smallpox from the planet.

Tegnell argued that “if other countries were led by experts rather than politicians, more nations would have policies like Sweden’s” and he may have been right. In the United States, for example, the Great Barrington declaration, which argued for a Swedish style approach and which Slavitt denounces in lurid and slanderous terms, was written by three highly-qualified, expert epidemiologists; Martin Kulldorff from Harvard, Sunetra Gupta from Oxford and Jay Bhattacharya from Stanford. One would be hard-pressed to find a more expert group.

The point is not that we should have followed the Great Barrington experts (for what it is worth, I opposed the Great Barrington declaration). Ecclesiastes tells us:

… that the race is not to the swift, nor the battle to the strong, neither yet bread to the wise, nor yet riches to men of understanding, nor yet favor to men of skill; but time and chance happeneth to them all.

In other words, the experts can be wrong. Indeed, the experts are often divided, so many of them must be wrong. The experts also often base their policy recommendations on factors beyond their expertise, including educational, class, and ideological biases, so the experts are to be trusted more on factual questions than on ethical answers. Nevertheless, the experts are more likely to be right than the non-experts. So how should one navigate these nuances in a democratic society? Slavitt doesn’t say.

Slavitt’s simple narrative–Trump bad, Biden good, Follow the Science, Be Kind–can’t help us as we try to improve future policy. Slavitt ignores most of the big questions. Why did the CDC fail in its primary mission? Indeed, why did the CDC often slow our response? Why did the NIH not quickly fund COVID research giving us better insight on the virus and its spread? Why were the states so moribund and listless? Why did the United States fail to adopt first doses first, even though that policy successfully saved lives by speeding up vaccinations in Great Britain and Canada?

To the extent that Slavitt does offer policy recommendations they aren’t about reforming the CDC, FDA or NIH. Instead he offers us a tired laundry list; a living wage, affordable housing, voting reform, lobbying reform, national broadband, and reduction of income inequality. Surprise! The pandemic justified everything you believed all along! But many countries with these reforms performed poorly during the pandemic and many without, such as authoritarian China, performed relatively well. All good things do not correlate.

Trump’s mishandling of the pandemic make it easy to blame him and call it a day. But the rot is deep. If we do not get to the core of our problems we will not be ready for the next emergency. If we are lucky, we might face the next emergency with better leadership but a great country does not rely on luck.

A Half Dose of Moderna is More Effective Than a Full Dose of AstraZeneca

Today we are releasing a new paper on dose-stretching, co-authored by Witold Wiecek, Amrita Ahuja, Michael Kremer, Alexandre Simoes Gomes, Christopher M. Snyder, Brandon Joel Tan and myself.

The paper makes three big points. First, Khoury et al (2021) just published a paper in Nature which shows that “Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.” What that means is that there is a strong relationship between immunogenicity data that we can easily measure with a blood test and the efficacy rate that it takes hundreds of millions of dollars and many months of time to measure in a clinical trial. Thus, future vaccines may not have to go through lengthy clinical trials (which may even be made impossible as infections rates decline) but can instead rely on these correlates of immunity.

Here is where fractional dosing comes in. We supplement the key figure from Khoury et al.’s paper to show that fractional doses of the Moderna and Pfizer vaccines have neutralizing antibody levels (as measured in the early phase I and phase II trials) that look to be on par with those of many approved vaccines. Indeed, a one-half or one-quarter dose of the Moderna or Pfizer vaccine is predicted to be more effective than the standard dose of some of the other vaccines like the AstraZeneca, J&J or Sinopharm vaccines, assuming the same relationship as in Khoury et al. holds. The point is not that these other vaccines aren’t good–they are great! The point is that by using fractional dosing we could rapidly and safely expand the number of effective doses of the Moderna and Pfizer vaccines.

Second, we embed fractional doses and other policies such as first doses first in a SIER model and we show that even if efficacy rates for fractional doses are considerably lower, dose-stretching policies are still likely to reduce infections and deaths (assuming we can expand vaccinations fast enough to take advantage of the greater supply, which is well within the vaccination frontier). For example, a half-dose strategy reduces infections and deaths under a variety of different epidemic scenarios as long as the efficacy rate is 70% or greater.

Third, we show that under plausible scenarios it is better to start vaccination with a less efficacious vaccine than to wait for a more efficacious vaccine. Thus, Great Britain and Canada’s policies of starting First Doses first with the AstraZeneca vaccine and then moving to second doses, perhaps with the Moderna or Pfizer vaccines is a good strategy.

It is possible that new variants will reduce the efficacy rate of all vaccines indeed that is almost inevitable but that doesn’t mean that fractional dosing isn’t optimal nor that we shouldn’t adopt these policies now. What it means is that we should be testing and then adapting our strategy in light of new events like a battlefield commander. We might, for example, use fractional dosing in the young or for the second shot and reserve full doses for the elderly.

One more point worth mentioning. Dose stretching policies everywhere are especially beneficial for less-developed countries, many of which are at the back of the vaccine queue. If dose-stretching cuts the time to be vaccinated in half, for example, then that may mean cutting the time to be vaccinated from two months to one month in a developed country but cutting it from two years to one year in a country that is currently at the back of the queue.

Read the whole thing.

The Becker-Friedman center also has a video discussion featuring my co-authors, Nobel prize winner Michael Kremer and the very excellent Witold Wiecek.

Two Vaccine Updates

First, in an article on new vaccine boosters in USA today there is this revealing statement:

Any revised Moderna vaccine would include a lower dose than the original, Moore said. The company went with a high dose in its initial vaccine to guarantee effectiveness, but she said the company is confident the dose can come down, reducing side effects without compromising protection.

Arrgh! Why wait for a new vaccine??? Fractional dosing now!

A microneedle patch for vaccines.

The same article also notes:

One of Moderna’s co-founders, MIT professor Robert Langer, is known for his research on microneedles, tiny Band-Aid-like patches that can deliver medications without the pain of a shot. Moderna has said nothing about delivery plans, but it’s conceivable the company might try to combine the two technologies to provide a booster that doesn’t require an injection.

The skin is highly immunologically active so you can give lower doses with a microneedle patch. The microneedles are sometimes made from sugar and don’t hurt. Microneedle delivery, however, can cause scars but I say apply the patch where the sun don’t shine and let’s go!

Second, Canada’s NACI has now endorsed mix and match for the AZ and Pfizer and Moderna vaccines. First Doses First has put Canada in very good shape (now ahead of the US in percent of the population with at least one dose) and this was always part of the FDF plan–delay second doses to get out more first doses and then, when supplies increase, give second doses, possibly with a better vaccine.

India Delays the 2nd Dose; Delaying 2nd Dose Improves Immune Response; Fractional Dosing

India has delayed the second dose to 12-16 weeks.

In other news, delaying the second dose of the Pfizer vaccine appears to improves the immune response (as was also found for the AstraZeneca vaccine). The latter is a news report based on a press release so some caution is warranted but frankly this was always the Bayesian bet since most vaccines have a longer time between doses as that helps the immune system. As Tyler and myself both argued, the short gap between the first and second dose was chosen to speed up the clinical trials not to maximize immunity. That was the right decision in the emergency but it was never the case that following the clinical trial regimen was “going by the science” no matter what Fauci said.

Many lives have been lost by not going to first doses first earlier, both here and in India.

Every country should move to a regimen in which the second dose comes at 12-16 weeks, even the United States, as this may improve the immune response and help other countries get a little bit ahead in their vaccine drives.

May I now also beat the drum some more on fractional dosing? Many people (not everyone) report that the second mRNA dose packs a wallop. I suspect that a half dose at 12-16 weeks would be plenty and that would free up significant capacity to vaccinate more people with first doses. We could also run some trials on half-doses for the young as a way to balance dosing and risk. Again this will matter for the rest of the world more than the United States but stretching doses in the United States will help the rest of the world and the arguments against stretching doses are now much diminished.

Atul Gawande and Zeke Emanuel Now Support Delaying the Second Dose

Many people are coming around to First Doses First, i.e delaying the second dose to ~12 weeks. Atul Gawande, for example, tweeted:

As cases and hospitalizations rise again, we can’t count on behavior alone reversing this course. Therefore, it’s time for the Biden admin to delay 2nd vax doses to 12 weeks. Getting as many people as possible a vax dose is now urgent.

Now urgent??? Yes, I am a little frustrated because the trajectory on the new variants was very clear. On January 1, for example, I wrote about The New Strain and the Need for Speed (riffing off an excellent piece by Zeynep Tufekci).  Still, very happy to have Gawande’s voice added to the cause. Also joining Gawande are the power trio of Govind Persad, William F. Parker and Ezekiel J. Emanuel who in an important op-ed write:

If we temporarily delay second doses …that is our best hope of quelling the fourth wave ignited by the B.1.1.7 variant. Because we did not start this strategy earlier, it is probably too late for Michigan, New York, New Jersey and the other Northeastern states. But it might be just in time for the South and California — the next places the more infectious strain will go if historical patterns repeat.

…Drug manufacturers selected the three- or four-week interval currently used between doses to rapidly prove efficacy in clinical trials. They did not choose such short intervals based on the optimal way of using the vaccines to quell a pandemic. While a three- or four-week follow-up is safe and effective, there is no evidence it optimizes either individual benefit or population protection.

…Some complain that postponing second doses is not “following the science.” But the scientific evidence goes far beyond what was shown in the original efficacy trials. Data from the United Kingdom, Israel and now the Centers for Disease Control and Prevention shows that first doses both prevent infection and reduce transmission. In people with prior infection, experts are beginning to recognize that a second dose could provide even less benefit. Following the science means updating policies to recognize new evidence rather than stubbornly maintaining the status quo.

Emanuel is on Biden’s COVID-19 task force so consider this op-ed running the flag up the flagpole. I predict Topol will fall next.

I would be surprised, however, if the US changes course now–too many people would then ask why didn’t we do this sooner?–but dose stretching is going to be important for the rest of the world. Why aren’t we doing more to investigate fractional dosing? Even if we went to half-doses on the second dose–the full second dose appears to be strong–that would still be a significant increase in total supply.

Addendum: I have argued for sending extra doses to Michigan and other hot spots such as NJ. Flood the zone! The Biden administration says no. Why? Production is now running well ahead of distribution as more than 50 million doses have been delivered but not administered. It would be a particularly good idea to send more single-shot J&J to reach hard to reach communities–one and done.

Power Up!

Two weeks ago I was bitten by the equivalent of a radioactive spider and now I have superpowers! Including the power of immunity and the power to fly! Awesome. As I said earlier, the SARS-COV-2 virus killed more people this year than bullets “so virus immunity is a much better superpower than bullet immunity!”

I got the J&J vaccine–one of the first in the world to do so–which seemed appropriate as I have been calling for first doses first and the J&J vaccine is single dose. I will probably supplement with Novavax at a later date when supplies are plentiful.

Addendum: Also, I can get free donuts at Krispy Kreme.

British Vaccine Efficiency

The British vaccination plan has been run very well. As this audience knows, the British delayed the second dose in order to get out more first doses quickly. A life-saving move. The British have also been targeting age and riskier workers very well. The excellent Witold Więcek (an Emergent Ventures prize recipient) has done a back of the envelope calculation which indicates how well the British are targeting.

Since the vaccines have been prioritised for the elderly, the infection fatality risk (IFR) for a typical vaccinated patient is higher than the average IFR in the population. However, we have to account for the fact that many of the early doses are given to health care workers and some of the other key workers. By late February 2021, in the UK around 55% of the vaccines went to people over 70 and over 95% of that age group has been vaccinated. In the US, however, while 55% of vaccines went to people over 65, close to 30% went to people younger than 50. We calculated IFR as an approximate weighted mean of age-specific infection mortality risks, using a meta-analysis estimate in Manheim et al., 2021.

Applying this IFR approach to real-world distributions of vaccine distribution, for UK we obtained 4.7% and for the US 3.2%, a remarkable difference. In other words, despite delivering twice the number of doses (and “running out” of highest risk individuals to vaccinate), a single dose of vaccine in the UK was still used 50% more effectively than in the US. (It should be noted, however, that the UK has a slightly older population than the US.)

Given less centralized health information, it’s hard to see how the US could target much better while also maintaining speed which is why, after the first round of vaccinating the nursing homes and the very elderly, I have leaned towards opening up more vaccination sites and prioritizing speed. So read this as a credit to the British rather than a demerit to the US. Other European countries, however, also have more centralized medical systems and yet have been far behind the British. It has struck me during this crisis how little these kind of system-wide policy variable seem to explain in the efficiency of the pandemic response overall.

Dose Stretching Policies Probably *Reduce* Mutation Risk

One objection to dose-stretching policies, such as delaying the second dose or using half-doses, is that this might increase the risk of mutation. While possible, some immunologists and evolution experts are now arguing that dose-stretching will probably reduce mutation risk which is what Tyler and I concluded. Here’s Tyler:

One counter argument is that letting “half-vaccinated” people walk around will induce additional virus mutations.  Florian Kramer raises this issue, as do a number of others.

Maybe, but again I wish to see your expected value calculations.  And in doing these calculations, keep the following points in mind:

a. It is hard to find vaccines where there is a recommendation of “must give the second dose within 21 days” — are there any?

b. The 21-day (or 28-day) interval between doses was chosen to accelerate the completion of the trial, not because it has magical medical properties.

c. Way back when people were thrilled at the idea of Covid vaccines with possible 60% efficacy, few if any painted that scenario as a nightmare of mutations and otherwise giant monster swarms.

d. You get feedback along the way, including from the UK: “If it turns out that immunity wanes quickly with 1 dose, switch policies!”  It is easy enough to apply serological testing to a control group to learn along the way.  Yes I know this means egg on the face for public health types and the regulators.

e. Under the status quo, with basically p = 1 we have seen two mutations — the English and the South African — from currently unvaccinated populations.  Those mutations are here, and they are likely to overwhelm U.S. health care systems within two months.  That not only increases the need for a speedy response, it also indicates the chance of regular mutations from the currently “totally unvaccinated” population is really quite high and the results are really quite dire!  If you are so worried about hypothetical mutations from the “half vaccinated” we do need a numerical, expected value calculation comparing it to something we already know has happened and may happen yet again.  When doing your comparison, the hurdle you will have to clear here is very high.

(See my Washington Post piece for similar arguments and additional references.).

Now here are evolutionary theorists, immunologists and viral experts Sarah Cobey, Daniel B. Larremore, Yonatan H. Grad, and Marc Lipsitch in an excellent paper that first reviews the case for first doses first and then addresses the escape argument. They make several interrelated arguments that a one-dose strategy will reduce transmission, reduce prevalence, and reduce severity and that all of these effects reduce mutation risk.

The arguments above suggest that, thanks to at least some effect on transmission from one dose, widespread use of a single dose of mRNA vaccines will likely reduce infection prevalence…

The reduced transmission and lower prevalence have several effects that individually and together tend to reduce the probability that variants with a fitness advantage such as immune escape will arise and spread (Wen, Malani, and Cobey 2020). The first is that with fewer infected hosts, there are fewer opportunities for new mutations to arise—reducing available genetic variation on which selection can act. Although substitutions that reduce antibody binding were documented before vaccine rollout and are thus relatively common, adaptive evolution is facilitated by the appearance of mutations and other rearrangements that increase the fitness benefit of other mutations (Gong, Suchard, and Bloom 2013; N. C. Wu et al. 2013; Starr and Thornton 2016). The global population size of SARS-CoV-2 is enormous, but the space of possible mutations is larger, and lowering prevalence helps constrain this exploration. Other benefits arise when a small fraction of hosts drives most transmission and the effective reproductive number is low. Selection operates less effectively under these conditions: beneficial mutations will more often be lost by chance, and variants with beneficial mutations are less certain to rise to high frequencies in the population (Desai, Fisher, and Murray 2007; Patwa and Wahl 2008; Otto and Whitlock 1997; Desai and Fisher 2007; Kimura 1957). More research is clearly needed to understand the precise impact of vaccination on SARS-CoV-2 evolution, but multiple lines of evidence suggest that vaccination strategies that reduce prevalence would reduce rather than accelerate the rate of adaptation, including antigenic evolution, and thus incidence over the long term.

In evaluating the potential impact of expanded coverage from dose sparing on the transmission of escape variants, it is necessary to compare the alternative scenario, where fewer individuals are vaccinated (but a larger proportion receive two doses) and more people recover from natural infection. Immunity developing during the course of natural infection, and the immune response that inhibits repeat infection, also impose selection pressure. Although natural infection involves immune responses to a broader set of antibody and T cell targets compared to vaccination, antibodies to the spike protein are likely a major component of protection after either kind of exposure (Addetia et al. 2020; Zost et al. 2020; Steffen et al. 2020), and genetic variants that escape polyclonal sera after natural infection have already been identified (Weisblum et al. 2020; Andreano et al. 2020). Studies comparing the effectiveness of past infection and vaccination on protection and transmission are ongoing. If protective immunity, and specifically protection against transmission, from natural infection is weaker than that from one dose of vaccination, the rate of spread of escape variants in individuals with infection-induced immunity could be higher than in those with vaccine-induced immunity. In this case, an additional advantage of increasing coverage through dose sparing might be a reduction in the selective pressure from infection-induced immunity.

…In the simplest terms, the concern that dose-sparing strategies will enhance the spread of immune escape mutants postulates that individuals with a single dose of vaccine are those with the intermediate, “just right” level of immunity, more likely to evolve escape variants than those with zero or two doses (Bieniasz 2021; Saad-Roy et al. 2021)….There is no particular reason to believe this is the case. Strong immune responses arising from past infection or vaccination will clearly inhibit viral replication, preventing infection and thus within-host adaptation…. Past work on influenza has found no evidence of selection for escape variants during infection in vaccinated hosts (Debbink et al. 2017). Instead, evidence suggests that it is immunocompromised hosts with prolonged influenza infections and high viral loads whose viral populations show high diversity and potentially adaptation (Xue et al. 2017, 2018), a phenomenon also seen with SARS-CoV-2 (Choi et al. 2020; Kemp et al. 2020; Ko et al. 2021). It seems likely, given its impact on disease, that vaccination could shorten such infections, and there is limited evidence already that vaccination reduces the amount of virus present in those who do become infected post-vaccination (Levine-Tiefenbrun et al. 2021).

I also very much agree with these more general points:

The pandemic forces difficult choices under scientific uncertainty. There is a risk that appeals to improve the scientific basis of decision-making will inadvertently equate the absence of precise information about a particular scenario with complete ignorance, and thereby dismiss decades of accumulated and relevant scientific knowledge. Concerns about vaccine-induced evolution are often associated with worry about departing from the precise dosing intervals used in clinical trials. Although other intervals were investigated in earlier immunogenicity studies, for mRNA vaccines, these intervals were partly chosen for speed and have not been completely optimized. They are not the only information on immune responses. Indeed, arguments that vaccine efficacy below 95% would be unacceptable under dose sparing of mRNA vaccines imply that campaigns with the other vaccines estimated to have a lower efficacy pose similar problems. Yet few would advocate these vaccines should be withheld in the thick of a pandemic, or roll outs slowed to increase the number of doses that can be given to a smaller group of people. We urge careful consideration of scientific evidence to minimize lives lost.

The Big Push: A Plan to Accelerate V-Day

In the Washington Post I have an extensive piece on accelerating progress to V-day, Vaccine or Victory day, the day everyone who wants a vaccine has gotten one. I cover themes that will be familiar to MR readers, including First Doses First, Fractional Dosing, Approving More Vaccines and DePrioritization to Expand Delivery. I won’t belabor these points here but the piece is useful at collecting all the arguments in one place and there are lots of authoritative links.

One point I do want to make is that all the pieces of the “Tabarrok plan,” if  you will, fit together. Namely, use First Doses First to make a big push to get as many people vaccinated with first doses as possible in the next 90 days. Approve more vaccines including Johnson & Johnson, AstraZeneca and others and make them available to anyone, anywhere–that is possible because these vaccines don’t require significant cold storage, J&J is a single shot and AZ is better with a second shot at 12 weeks or later all of which eases distribution.

…some people argue that adding a third (or fourth) vaccine might not help because of persistent delivery logjams at the state and local levels. But we know there is unused distributional capacity, even for the supply we do have. The United States is currently administering about 1.5 million coronavirus vaccine shots per day. While that sounds like a lot, for comparison consider that in September — during the pandemic, when social distancing measures were in full effect — we vaccinated for the seasonal flu in some weeks at the rate of 3 million people a day.

There are two main reasons the rollout has been so slow. First, the Moderna and especially the Pfizer vaccines require ultracold storage. (The Johnson & Johnson and AstraZeneca doses can be stored at ordinary refrigerator temperatures.) Second, we have tried to prioritize vaccinations using a confusing mishmash of age, health conditions and essential-worker status that differs by state and sometimes even by county. “Confirming such criteria is complicated at best, and it’s probably not even feasible to try under conditions of duress,” as Baylor’s Hotez puts it.

Arguments continue about prioritization lists, and the idea of tossing them entirely would cause a political fight. But there is a compromise at hand: Quickly approve the Johnson & Johnson and AstraZeneca vaccines and make them — and only them — available to anyone, anywhere. Keeping things simple is a sure way to increase total vaccinations. With no cold-storage requirement, the new vaccines could be administered by any of the 300,000 pharmacists and more than 1 million physicians in the United States authorized to deliver vaccines, most of whom are not now giving Pfizer or Moderna shots.

Canada Needs a New Vaccination Strategy

The US vaccination rollout has been deadly slow, inefficient, and chaotic. It has also been one of the best in the world. Canada, for example, is far behind the US on vaccination.

The Canadian deficit is mostly because they don’t have enough vaccine. Canada bought doses but they didn’t invest in capacity and a deal with China fell through. As a result, Canada won’t be getting lots of vaccine until March or April. Operation Warp Speed invested billions in the Modern vaccine and in early purchases of the Pfizer vaccine and thus got first dibs. The Americans are also not allowing vaccine to be exported to Canada. (We could at least give them access to our AstraZeneca factory!).

Regardless of blame, this puts Canada in a precarious situation. Death rates aren’t as high as in the United States but with new variants exploding, Canada is running a big risk. To get Canadians vaccinated more quickly–including my mother–Canada needs to find ways to stretch their vaccine supply–that means First Doses First, half dosing, intradermal delivery and other dose stretching strategies should be considered.

Many other countries are in a much more worse position than either the United States or Canada.

Had Covid? You May Need Only One Dose

The barriers are breaking. Step by step we move closer to First Doses First. New results from a small-scale study suggest that people who have had COVID have strong reactions to the first dose and may not need the second dose.

NYTimes: Based on these results, the researchers say, people who have had Covid-19 may need only one shot.

“I think one vaccination should be sufficient,” said Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai and an author on the study. “This would also spare individuals from unnecessary pain when getting the second dose and it would free up additional vaccine doses.”

…People who have had Covid seem to be “reacting to the first dose as if it was a second dose,” said Akiko Iwasaki, an immunologist at the Yale School of Medicine. So one dose is probably “more than enough,” she said.

A study published earlier this month reported that surviving a natural infection provided 83 percent protection from getting infected again over the course of five months. “Giving two doses on top of that appears to be maybe overkill,” she added.

So for the 25 million to 100 million Americans who have already been infected by COVID it may be better for them personally to delay the second dose. In short, a significant fraction of second doses have little to no value. This (unsurprising) finding means that First Doses First is an even better strategy even if we can’t condition doses on previous infection.

Most important, First Doses First gets more people significant immunity faster which is good for the vaccinated and also drives down R which is good for society as a whole, even the unvaccinated.

The Biden administration has been more pro-active than the Trump administration on tests and vaccination and has already made some goods calls on getting more doses out faster. I hope they continue to be bold. We need quick, bold, and decisive action.

To Every One Who Has, More Will Be Given

From an email to Fairfax County teachers:

Due to a decrease in vaccine allocation, we are temporarily reducing appointment availability over the coming weeks. Vaccine supply is fluid across the country, and we are matching currently scheduled appointments to anticipated inventory.

We are pleased to share that more than 22,000 Fairfax County Public Schools teachers and employees have already been able to schedule their first shot.  At this time we are honoring those who have current appointments. Should our vaccine supply not be sufficiently replenished, we will suspend initial appointments (first doses) for eligible individuals in 1b and prioritize those who require their second vaccine dose in the weeks to come.

It’s really quite stunning when you think about it.

Hat tip: Max.

Preparing for a Pandemic: Accelerating Vaccine Availability

In Preparing for a Pandemic, (forthcoming AER PP), by myself and a host of worthies including Susan Athey, Eric Budish, Canice Prendergast, Scott Duke Kominers, Michael Kremer and others equally worthy, we explain the model that we have been using to estimate the value of vaccines and to advise governments. The heart of the paper is the appendix but the paper gives a good overview. Based on our model, we advised governments to go big and we had some success but everywhere we went we were faced with sticker shock. We recommended that even poor countries buy vaccines in advance and that high-income countries make large investments in vaccine capacity of $100b or more in total.

It’s now obvious that we should have spent more but the magnitudes are still astounding. The world spent on the order of $20b or so on vaccines and got a return in the trillions! It was hard to get governments to spend billions on vaccines despite massive benefit-to-cost ratios yet global spending on fiscal support was $14 trillion! Even now, there is more to be done to vaccinate the world quickly, but still we hesitate.

I went over the model for Jess Hoel’s class and we also had a spirited discussion of First Doses First and other policies to stretch the vaccine supply.

We Will Get to Herd Immunity in 2021…One Way or Another

By July it will all be over. The only question is how many people have to die between now and then?

Youyang Gu, whose projections have been among the most accurate, projects that the United States will have reached herd immunity by July, with about half of the immunity coming from vaccinations and half from infections. Long before we reach herd immunity, however, the infection and death rates will fall. Gu is projecting that by March infections will be half what they are now and by May about one-tenth the current rate. The drop will catch people by surprise just like the increase. We are not good at exponentials. The economy will boom in Q2 as infections decline.

If that sounds good bear in mind that 400,000 people are dead already and the CDC expects another 100,000 dead by February. We have a very limited window in the United States to make a big push on vaccines and we are failing. We are failing phenomenally badly.

To understand how bad we are failing compare with flu vaccinations. Every year the US gives out about 150 million flu vaccinations within the space of about 3 months or 1.6 million shots a day. Thus, we vaccinate for flu at more than twice the speed we are vaccinating for COVID! Yes, COVID vaccination has its own difficulties but this is an emergency with tens of thousands of lives at stake.

I would love it if we mobilized serious resources and vaccinated at Israel’s rate–30% of the population in a month. But if we simply vaccinated for COVID at the same rate as we do for flu we would save thousands of lives and hundreds of billions of dollars in GDP. The comparison with flu vaccinations also reminds us that we don’t necessarily need the National Guard or mass clinics in stadiums. Use the HMOs and the pharmacies!

And let’s make it easier for the pharmacies. It’s beyond ridiculous that we are allowing counties to set their own guidelines for who should be vaccinated first. We need one, or at most 50, set of guidelines and lets not worry so much at people jumping the queue. (The ones jumping the queue are probably the ones who want to get back to the bars and social life the most so vaccinating them first has some side benefits.)

Of course, the faster we vaccinate the more vaccine quantities will become the binding constraint which is why we also need to approve more vaccines, move to First Doses First (delay second doses like the British), and use Moderna half-doses. Fire on all cylinders!

Time is of the essence.

Hat tip: Kevin Bryan and Witold Wiecek.

Thursday assorted links

1. Mental health slow boil pandemic edition.  And what is the implied discount rate here?

2. Are Israeli flying ambulances on the way?

3. What wine meant to Roger Scruton.  Not my view of course.

4. The “telephone problem” of sequential communication may lead to excess negativity.

5. Marginal Revolution University supply and demand instructional unit for high schools (and others!).

6. Dose delay and viral resistance, recommended.  First Doses First is looking better all the time.

7. Did Jupiter kill Venus?  And Margo St. James has passed away.