Category: Medicine

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.

Protection against dengue?

The dengue virus uses a particular protein, called Non-Structural Protein 1 (NS1), to latch onto the protective cells around organs. It weakens the protective barrier, allowing the virus to infect the cell, and may cause the rupture of blood vessels. The research team’s antibody, called 2B7, physically blocks the NS1 protein, preventing it from attaching itself to cells and slowing the virus’s spread. Moreover, because it attacks the protein directly and not the virus particle itself, 2B7 is effective against all four dengue virus strains.

That is cited by the excellent Jodi Ettenberg, from new January 2021 research.  If I  hear more I will let you know.

Praise the British

Britain has fully vaccinated more people against #COVID19 than every other nation on earth combined.

Link and picture here.  That is as of January 13, at least.  You may recall my previous and much-attacked July Bloomberg column suggesting that along a number of dimensions the UK pandemic response actually was quite good.

Addendum: Numerical correction from Alex on America, though you still can praise the British.

California Covid-19 Vaccine Availability

The State of California has approved giving the COVID-19 vaccine to people age 65 and older. We are calling hospitals and pharmacies daily to check which are currently administering vaccines. We called more than 100 on Thursday, January 14th, and aim to call several hundred on Friday, January 15th. Our goal is getting shots in arms as quickly as possible for you or your loved ones.

We intend to call all the vaccination sites in California. If you have a missing location to report, or think we have incorrect contact information, please let us know.

We’ve also compiled county policies on vaccination here.

Here is the link, there should be more projects like this one — think matching models!

The Magical Extra Doses and Supply Chain Optimization

1-ml syringe design yields 2 micro literes and standard syringe and needle hub yield 84 micro liters on average.
Image from Wikipedia, Low dead space syringe.

As pharmacists began vaccinations using the Pfizer vaccine some of them discovered that it was possible to extract a 6th or even 7th dose from a standard 5-dose vial. Where were the extra doses coming from? The fortuitous discovery was not due to over-filling. The vials contained just 5 doses when using standard syringes. But some of the vaccine distribution sites had access to low dead-volume syringes, syringes that leave less vaccine trapped between the plunger and needle — the “dead volume” — after a shot is given. Thus, less vaccine was wasted in the syringe and more available for putting into arms using the low dead-volume syringes.

This is quite remarkable. Increasing vaccine supply by 20% by building more factories could cost billions. We should do that, it would be worth it. But in this case, we managed to increase supply by at least 20% use a relatively inexpensive redesign of the syringe. What this indicates is the importance of thinking along the entire supply chain for opportunities for optimization.

The catch? Not all syringes provided by Operation Warp Speed and Pfizer are low dead-volume syringes so not every vaccine distribution site is getting the extra doses. We do need to invest more in the syringe supply chain.

Fact of the day, get to those rooftops!

Pepvar’s first goal should be supporting the production of enough doses to vaccinate the entire world within a year. It is estimated that building such capacity for an mRNA vaccine like Moderna’s would cost less than $4 billion — that’s significantly less than the U.S. government already spends each day on Covid-19 relief — with the cost about $2 per dose. Of course, making the vaccines is just the first step: Pepvar must

People, even if that estimate is off by a factor of ten or more…etc.  Here is the NYT link, bJames KrellensteinPeter Staley and .

My Conversation with the excellent Noubar Afeyan

Among his other achievements, he is the Chairman and co-founder of Moderna.  Here is the audio and video and transcript.  Here is part of the summary:

He joined Tyler to discuss which aspect of entrepreneurship is hardest to teach, his predictions on the future of gene editing and CRISPR technology, why the pharmaceutical field can’t be winner takes all, why “basic research” is a poor term, the secret to Boston’s culture of innovation, the potential of plant biotech, why Montreal is (still) a special place to him, how his classical pianist mother influenced his musical tastes, his discussion-based approach to ethical dilemmas, how thinking future-backward shapes his approach to business and philanthropy, the blessing and curse of Lebanese optimism, the importance of creating a culture where people can say things that are wrong, what we can all learn by being an American by choice, and more.

Here is one excerpt:

AFEYAN:

I should point out, Tyler, what these people don’t yet realize is that mRNA, in addition to being unique in that it’s really the first broadly applied code molecule, information molecule that is used as a medicine and with all the advantages that come with information — digital versus analog — or where you actually have to do everything bespoke, the way drugs usually work.

The other major advantage that it has is that it is something that is actually taking advantage of nature. There was a lot of know-how we had going into this around how the process could be done. In fact, let me tell you the parallel that we used.

We have a program in cancer vaccines. You might say, “What does a cancer vaccine have to do with coronavirus?” The answer is the way we work with cancer vaccines is that we take a patient’s tumor, sequence it, obtain the information around all the different mutations in that tumor, then design de novo — completely nonexistent before — a set of peptides that contain those mutations, make the mRNA for them, and stick them into a lipid nanoparticle, and give it back to that patient in a matter of weeks.

That has been an ongoing — for a couple of years — clinical trial that we’re doing. Well, guess what? For every one of those patients, we’re doing what we did for the virus, over and over and over again. We get DNA sequence. We convert it into the antigenic part. We make it into an RNA. We put it in a particle. In an interesting way, we had interesting precedents that allowed us to move pretty quickly.

And at the close:

Imagine if all of us were also born imagining a better future for ourselves. Well, we should be, but we’ve got to work to get that. An immigrant who comes here understands that they’ve got to work to get that. They have to adapt. The problem is, if you’re born here, you may not actually think that you’ve got to work to get that. You might think you’re born into it.

This will be a funny thing to say, and I apologize to anybody that I offend. If we were all Americans by choice, we’d have a better America because Americans by choice, of which I’m one, actually have a stronger commitment to whatever it takes to make America be the place I chose to be, versus not thinking about that as a core responsibility.

Definitely recommended, he is working to save many many lives, and with great success.

Ireland fact of the day, coming soon to a state near you

Some experts estimate this could mean, if we do not accelerate the pace of vaccination, one million deaths for the United States.

N95 and KN95 Masks

Mask use is near 100% here in Northern Virginia. I am surprised, however, how many people continue to use simple cloth masks when much better N95s and KN95s (Chinese equivalent to N95s) are widely available. Gold standard appears to be the Respokare N95s which are NIOSH approved (under Innonix) but are quite expensive. I also like these cheaper KN95s from Kingfa which are not NIOSH approved. Some of the Chinese masks are garbage but limited testing by the CDC suggests the Kingfa are pretty good. No guarantees. Use your own judgment.

No Learning Without Risk

Here’s something from a paper that I am working on. The context is why first doses first makes more sense the greater the uncertainty but the point made is larger. No indent.

An important feature of First Doses First (FDF) and other policies such as fractional dosing is that they are reversible. In other words, FDF contains an option to switch back to Second Doses First (SDF). Options increase in value with uncertainty (Dixit and Pindyck 1994). Thus, contrary to many people’s intuitions, the greater the uncertainty the greater the value of moving to First Doses First. Indeed, the value of the option can be so high that one might want to move to First Doses First even if it were worse in expectation. For example, if the expected efficacy of the first dose were just 45% then in expectation it would be worse than Second Doses First (95% efficacy) but if there were lots uncertainty around the 45% expected efficacy it might still be better to switch to First Doses First. If there was a 75% chance that the efficacy of the first dose was 30%, for example, and a 25% chance that it was 90% (.75*.3+.25*.90=45%) then under reversibility one would still want to switch to First Doses First to learn whether the true efficacy was 30% or 90%.*

Put differently shifting away from the default strategy to an alternative such as FDF or fractional dosing might be considered to be “risky”. But in this context, learning requires risk. When learning is desirable, it is also desirable to take on risk. Risk aversion can prevent learning and thus can be dangerous.

If FDF is worse in expectation than SDF then it would be optimal to switch to the most minimal form of FDF necessary to learn about the true efficacy rate. In other words, to run an experiment. If FDF is superior in expectation to SDF then it might also be better to run an experiment before switching but not necessarily. If FDF is superior in expectation to SDF then the cost of running the experiment is keeping the policy with lower expected value while the experiment is running. If these costs are high then switching immediately is better.

It would take at least 16 weeks, for example, to run an experiment on extending dosing from 3 weeks to 12 weeks (including, optimistically, just 1 week to setup the experiment). As of early January 2021, confirmed cases in the United States are increasing at the rate of 200,000 per day or 1,400,000 per week. Thus there could be 22,400,000 new confirmed cases in the time it takes to run the experiment. At a case fatality rate of 1.7% that means 380,800 new deaths. If First Doses First reduces the infection rate in expectation by 10% that would imply that running the experiment has an expected cost of 38,080 lives.

At these rates, more lives could be saved in expectation by switching to the policy with higher expected value and simultaneously running experiments. Randomized trials that explicitly test the impact of dosing timing, fractional dosing and different timings of additional doses on severe, symptomatic and asymptomatic infections, and also on transmission should be incorporated as part of roll-out plans (Kominers and Tabarrok 2020, Bach 2021). However, roll-out of modified plans should not wait until these trial results are known; instead, plans should be adjusted as new information emerges. Most notably the British moved to First Doses First and they approved the AstaZeneca vaccine on December 30, 2020 and the consequences of both of these decisions should be monitored very closely to help improve decisions in other countries.

*This assumes that one could learn the true efficacy rate quickly enough relative to the ongoing pandemic to benefit from the new information. One might respond that in principle SDF also contains an option to switch to FDF but this option is valueless since Second Doses First provides no opportunity to learn. Only under First Doses First do we learn valuable new information.

Approve the AstraZeneca Vaccine Now!

Here’s Marty Makary, M.D., a professor of surgery and health policy at the Johns Hopkins University School of Medicine:

Finally, the FDA needs to stop playing games and authorize the Oxford-AstraZeneca vaccine.  It’s safe, cheap ($2-$3 a dose), and is the easiest vaccine to distribute. It does not require freezing and is already approved and being administered in the United Kingdom.

Sadly, the FDA is months away from authorizing this vaccine because FDA career staff members insisted on another clinical trial to be completed and are punishing the company for inadvertently giving a half-dose of the vaccine to some people in the trial.

It’s like the FDA is holding out, pontificating existing excellent data and being vindictive against a company for making a mistake while thousands of Americans die each day.

Ironically, those in the Oxford-AstraZeneca trial who inadvertently received half the initial vaccine dose had lower infection rates. And this week Dr. Moncef Slaoui, the chief adviser to Operation Warp Speed, acknowledged that using half a dose might be a good broader strategy for the U.S. to double our supply as long our supply is severely constrained. That’s a good strategy that makes sense.

See also my post The AstraZeneca Factory in Baltimore. Thousands of people are dying every day. We have a vaccine factory ready to go. The FDA should lifts its ban on the AstraZeneca vaccine.

The end of the Swedish model

The government this week proposed an emergency law that would allow it to lock down large parts of society; the first recommended use of face masks came into force; and the authorities gave schools the option to close for pupils older than 13 — all changes to its strategy to combat the pandemic.

“I don’t think Sweden stands out [from the rest of the world] very much right now,” said Jonas Ludvigsson, professor of clinical epidemiology at Karolinska Institutet in Stockholm. “Most of the things that made Sweden different have changed — either in Sweden or elsewhere.”

…Sweden has reported more than 2,000 Covid-19 deaths in a month and 535 in the past eight days alone. This compares with 465 for the pandemic as a whole in neighbouring Norway, which has half the population. As Sweden’s King Carl XVI Gustaf said just before Christmas: “We have failed.”

Here is more from the FT.  U.S. Covid deaths per day have now exceeded 4,000 for some days, and they are running at about 50% of the normal number for total daily deaths.  And no, it is not that the payments to classify these as Covid deaths have increased, rather the virus and the deaths have increased.  So the “no big deal” question we now can consider settled?  The new and more contagious strains haven’t even started playing a major role yet in the United States.

“Second Doses” post-mortem

The most striking thing about the Biden administration shift to a version of “First Doses First” is how little protest there has been.  Given how many public health experts were upset about the idea only a few days ago, you might expect them to organize a Wall Street Journal petition from hundreds of their colleagues: “Biden administration proposal endangers the lives of millions of Americans.”

But of course they won’t do that.  Some of that is pro-Democrat partisanship, but that is not even the main factor.  One reason is that public health experts, with their medical and quasi-medical backgrounds, typically have very little sense of how to respond in the public arena if challenged.  For instance, not a single one stepped forward with a calculation to defend “Second Doses.”  They are not especially good at “the internet rules of the game,” which of course are now supreme (not always for the best, to be clear).

The second and probably most important reason is that, as I had explained, sins of omission are treated as far less significant than sins of commission.  Now that a version of “First Doses First” is on the verge of becoming policy, to do nothing about that is only a sin of omission, and thus not so bad.  Remarkable!  Status quo bias really matters here.

I haven’t seen a single peep on Twitter opposing the new policy.

Just keep all this in mind the next time you see a debate over public health policy.  There is often less behind the curtain than you might think.

First Doses First, coming soon to a state near you…

Of course on this particular issue, Alex was the one who started the intellectual campaign…