Well, here I am with the first “In the Pipeline” post of 2021, and damn itall, I’m right back to the stuff I was writing about last time. I still expect this year to be the time when we beat back the coronavirus pandemic, and (as a minor side effect for me) to be the year when I can spend more time blogging about other things than viruses and vaccines. But that time is not yet.
No, definitely not. There are a lot of things happening right on top of each other at the moment, and it’s impossible to say yet how they’re going to balance out. On the plus side, we have two vaccines approved in the US, and other countries are starting to use the Oxford/AstraZeneca vaccine or one of the Chinese vaccines. And we have more promising candidates that will be reporting very soon (J&J and Novavax). The minus side is that we’re going to need those very much, because manufacturing and distribution constraints are very real problems. We can argue (a lot) about those, their extents, who’s at fault or not, and all the rest, but I think that we can stipulate with no problem that they are indeed constraints. We have to get a large number of people vaccinated in a short period of time, the largest in the shortest, and as it stands right now neither of those numbers are anywhere near what we need.
I have every expectation that the pace of vaccination will pick up. But the other factor at work is the new coronavirus variant. Since I wrote that post, it’s become even more clear that yes, B.1.1.7 is indeed more infectious. The data from the UK are no longer consistent with its numbers being due to any sort of statistical accident, and it’s now been reported in numerous countries and several US states. At this point, it seems likely that it may follow the same pattern in those areas – and in the US – that it did in the United Kingdom, spreading more rapidly until it becomes the dominant strain in these populations.
That’s not good. Reports so far don’t show B.1.1.7 leading to more severe infections, but spreading the same disease we have now more quickly is still one of the last things we need. The latest data would seem to point to increased viral load in the upper respiratory tract as a big part of the problem – people are presumably shedding more infectious particles more quickly, which would certainly do it. There are many people talking about the cellular entry part of the infection process and whether B.1.1.7 is better at that, but I’m still reading up on the details. That could well be what leads to the increased viral load, but there are other possibilities, too. We’re going to know more about the details, and soon – a huge amount of work is going on in real time – but the increased R for this variant seems hard to refute.
So it’s the UK that’s in the worst shape with this variant right now, from what we can see, and what are they doing about it? This Helen Branswell piece at Stat will get you up to speed. As many will have heard, there are proposals from the British government to delay the second dose of the existing vaccines in order to get first doses into as many people as possible. It appears that our existing vaccines do indeed protect against B.1.1.7 infection, although more data on that would be welcome, but they sure don’t protect the people that aren’t dosed with them; on that we can all agree.
The delayed-dose idea had been floated before, and I wasn’t exactly an early adopter, but the more contagious version of the virus has made me reconsider. But as I was going on about on Twitter the other day, we have to be clear that this is, in fact, an experiment on the population. It seems likely that delaying these doses will likely work out OK. But we don’t have much evidence either way. I’m in favor of doing it, but I’m not happy about ending up in that position. I don’t trust immunology to always work the way that I think it should work, but it seems that we have little choice.
And by “we”, I mean all of us. As mentioned, B.1.1.7 is showing up around the world, including areas whose medical capacities are already being strained. The U.S. is very much included – look, for example, at the situation in Southern California. If things go badly, we could be seeing a big wave of this variant across many parts of the country in the next weeks, and it could be spreading much faster than our vaccination program can knock things back down. We have to get ready for that possibility, and there are already proposals here to adopt the delayed-second-dose protocol. Just in the last day or so, in fact, there’s been another proposal to use 50µg doses of the Moderna vaccine instead of the 100µg doses authorized in the EUA. Moncef Slaoui pointed out that the data submitted by Moderna show that the two doses produce similar immune responses in the 18-55 age group.
That’s another one that you can say will probably work, but there are things to worry about, both in the Moderna dosage idea and the general delay-the second-dose plan. I’ve been watching some very competent people argue these points both ways: here’s Florian Krammer with the possibility that these ideas could end up generating more resistant variants of the coronavirus. The Stat article linked above has similar worries from Paul Bieniasz at Rockefeller and Isabella Eckerle in Geneva, along with other experts who still think it’s the right way to go. But the worries are not just scaremongering from randos online or anonymous bureaucrats who don’t want to fill out more forms; it’s a real possibility, and its chances have to be weighed against the effects of the greater spread of the existing variant with slower vaccination schedules. Both of these could lead to very bad outcomes. Not dosing more people could exacerbate the problem of regions getting overwhelmed with the more contagious variant, with needless deaths due to the loss of hospital capacity. But if we spread out such vaccinations too much and manage to generate another variant that partially or even completely escapes the existing vaccine response, we will be in even worse shape.
I do not know how to make this decision. I really don’t. We have degrees of harm, probabilities of harm, logistics, timing, public health capabilities, politics and more to consider, and not a lot of time in which to consider them. Anyone who uses the phrase “no-brainer” to describe this call should be dropped from your list of people to take advice from. This is the opposite: it’s a decision that all our brainpower may still not be sufficient to make clear. But we’re going to have to make it anyway.