How many COVID vaccine doses do you need?
Vaccine rollout has had its challenges but we’re starting to see some real movement here - over 60 million doses given and almost 20 million people completing the full vaccination protocol.
When you add in the 28 million confirmed COVID cases along with the probably 80 million more unreported cases, it looks like we’re really getting somewhere.
Of course, there are caveats here before you start just adding up the numbers and assuming that we’re rapidly approaching herd immunity. There’s overlap in the people who are vaccinated with the people who have been infected. There’s the fact that the unreported cases are just estimates that have very wide confidence intervals. And there’s the lack of certainty we have about just how long immunity lasts for after you’ve had been infected.
But even if some of those details obscure our ability to measure infections with precision, the big picture is the same: really promising.
Now, the goal here is to get back to normal life and to minimize the death and suffering until we do. That means we need herd immunity.
How do we get to herd immunity faster?
This is straightforward - we vaccinate more people quickly.
But getting there is more difficult. Right now our limited supply of approved vaccines means that demand is greatly outpacing supply.
The anecdotes I’m hearing match up with the data - vaccine appointments are hard to come by and our allocation strategy is still too convoluted. This is getting better slowly and should continue to improve as manufacturing ramps up.
Unfortunately, we can’t just spend money to make the vaccines appear more quickly.
So we’re left with the challenge of allocating limited numbers.
Should we be following the standard protocols observed in the clinical trials of two doses spaced 3-4 weeks apart or should we do a “First Dose First” strategy? The New England Journal of Medicine just published a debate style document discussing this question. You can read it here.
What is the “First Dose First” strategy?
First Does First means that you give out as many first doses as you can and then delay the second dose until manufacturing ramps up.
The argument for this strategy is pretty straightforward: getting more shots into more arms spreads immunity out more widely.
We know two major pieces of information that make this an appealing strategy:
We start to see real world protection from both the Moderna and Pfizer vaccines before a second dose is given. I wrote about this in previous newsletters.
The vaccines seem to be effective against the new COVID variants that have emerged and are rapidly spreading, so time is of the essence in getting the vaccine widely distributed more quickly.
And then there’s the big reason to make this adjustment, which is that getting first doses out quickly may lead to a faster end to the pandemic, meaning that questions about immune durability would become moot.
“First Dose First” makes sense, so what’ the holdup? I want my shot!
There are two major risks of just giving out first doses. And unfortunately they’re basically impossible to quantify.
The first risk is about the virus itself - if a single shot induces incomplete immunity, there’s a new evolutionary pressure that this puts on the virus to mutate in order to evade our defenses. What if this pressure accelerates the evolution of new variants that can escape the vaccines that we have?
The second risk is the unintended societal consequence of changing our vaccination strategy in the middle of roll out:
“Many people are skeptical of vaccines, fearing that the speed of development has necessitated cutting corners and that political pressure has influenced vaccine recommendations. Suddenly changing dosing recommendations puts public confidence at serious risk and will impede willingness to be vaccinated at all. Cases of Covid-19 have already occurred in vaccine recipients, as was seen in the phase 3 trials, which will raise questions about the delayed-second-dose strategy and erode trust in the vaccine rollout. If these breakthrough cases appear to occur more frequently before the second, delayed dose, confidence will be further compromised, ultimately delaying the end of the pandemic and social and economic recovery.”
So what’s a policymaker to do?
This is why there’s no such thing as “follow the science”
Following the science can mean that each of these strategies makes sense:
You can look at the data showing an antibody response to the first dose along with a reduction in infections before second dose administration and conclude that “First Dose First” is the way forward
Alternatively, you can say that the studies only tested a two dose regimen, so it’s an unfair extrapolation of the science that we have.
Ultimately, we’re making decisions with incomplete information about the risks and benefits.
Here’s what we know about a one dose regimen
We can say with near certainty that it’s adequate to give a single dose to anyone who has been infected with COVID.
One dose after infection seems to augment the immune response and provide real protection against another infection.
We’ve seen it over and over again in trials. Take a look at this. Or this. Or this. Or this. The New York Times even wrote about it. So I think the story is clear here: after infection, one vaccine dose is ok.
The other thing that we can conclude is that there is clearly some protection after the first dose of each of these vaccines. This story appears clear here: the first dose reduces but doesn’t eliminate infection risk.
And perhaps a single dose regimen is even better than we might think at first glance:
“The authors also report a vaccine efficacy of 52.4% from after the first dose to before the second dose, but in their calculation, they included data that were collected during the first 2 weeks after the first dose, when immunity would have still been mounting.1 We used documents submitted to the Food and Drug Administration2 to derive the vaccine efficacy beginning from 2 weeks after the first dose to before the second dose (Table 1). Even before the second dose, BNT162b2 was highly efficacious, with a vaccine efficacy of 92.6%, a finding similar to the first-dose efficacy of 92.1% reported for the mRNA-1273 vaccine (Moderna).”
While there is certainly risk of delaying a dose for much longer than was tested in the clinical trials, the weight of the evidence has started to convince me that delaying second doses make sense.
The selective pressures to encourage viral mutations are certainly concerning, but risks here needs to be balanced.
With rapidly falling rates of infection and hospitalization around the country, now may be the time to move fast to reduce transmission and bring this pandemic to a close.
This is a time to be optimistic - the end is in sight.
After writing a lot about how bad things look ahead, I’m very encouraged. Things are looking up.
More to come later this week on what life should look like after you’ve already been vaccinated.
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