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Monday 26 July 2021

Passport to Pimlico... (other districts also have nightclubs)

Warning: The following article contains opinions. 

This weekend saw a moot of loons in Trafalgar Square, coming together in a sort of loose conglomerate of wacky witlessness. In a wonderful mirror of the Brexit referendum, an uncritical conclave of abject stupidity came together and sounded its barbaric yawp as a disparate one. And what did they want you to hear?

That the whole of healthcare and medical science, having moved hell and high water to protect us and keep us safe for the last year and a half, should be rounded up and subject to a Nuremberg-style trial. Of course, they don't mean anything as well-organised and sanctioned by the world community as Nuremberg so much as they mean some sort of drumhead, with the upturned drum being played by the musically inept Laurence Fox rather more competently than he plays guitar or sings, no doubt. I'm going to be one of the few who stands out and suggests people getting their scientific information from the least talented Fox, the deeply dubious Right Said Fred and others of such remarkable intellectual stature isn't something we should be surprised about. I'm fairly sure the regular long-time readers of this and related corners of the interweb are reaching for James O'Brien's tin about now. We've been warning against the sort of thinking that leads to this for decades. It is, in fact, why this place even exists.

That's really not the subject of this piece, though. What IS the subject, however, is one of the things they were protesting against; vaccine passports.

I'm probably going to be largely on my own in what I'm about to say, but I still feel it needs saying. Let me start with my limiting statement of the problem, then.

The most positive thing I can say about vaccine passports is 'better than nothing - maybe'.

Now for the qualification.

First, I'm talking about vaccine passports in isolation, i.e., absent any other mitigations. That's really important, because vaccine passports CAN be a really good thing when coupled with other measures, such as those I discussed in Qualified Immunity. On their own, though, they in fact increase risk in some ways while mostly only providing the illusion of reduced risk in others.

The problem lies entirely in the assumptions we bring to the table when assessing measures like this. In this case, some of those assumptions are things we talked about in a slightly different context than this, which is itself a problem. The risk is transmission. Let's look, then, at the impact of vaccine passports on transmission.

The single most important factor to remember is this; being vaccinated does nothing to prevent infection or transmission. There's a window of transmissibility when vaccinated, that runs from not long after infection. It's hugely variable, but there are sufficient data to draw some good conclusions. We have cases for every variant, for example, in which the time of exposure is known with good certainty, and we can measure the time between that and the time it takes for viral load to reach levels sufficient to be picked up in a PCR test.

Here's what being fully vaccinated does, then:

First, you get infected. It only takes a single viron, contrary to popular belief, but it's also the case that this single viron must successfully bind to a cell and inject its RNA. More virons = greater probability of successful binding. In all probability, an invader will have bound and your cells will be replicating the virus before your immune system has woken up to its presence. At some point, you reach peak infectiousness. Your immune system is working, and eventually quells the invader, with the help of the roadmap provided by the vaccine.

As a result, the vaccine pulls the end of the infectiousness window closer to the start, but it doesn't close it. What about the start of the window?

That's a bit trickier, because there are competing variables involved, the most important being the replication rate of the virus. So, virus invades, binds, injects, cells replicate. Immune system responds, gets to work on virus. As we've seen (well worth reading the above linked piece Qualified Immunity for a fuller picture), the immune system does this by throwing things at the virus and seeing what sticks. Once it finds something that properly binds to the virus and stops the virus binding to the cell, it gets to work making that thing, the antibody, in huge amounts.

Of course, the immune system, like all things oriented in spacetime, works at a finite speed. The same is true of viral replication. As an aside, these competing variables are the very definition of an evolutionary arms race. I'll be coming back to this, as it's critical to my conclusion.

At this point, the important thing is how the virus replicates in the presence of antibodies. For obvious reasons, this isn't binary. It's not a matter of having the antibodies therefore no replication. If the virus is replicating faster than the antibodies can be produced, you have breakthrough infection. In fact, the virus doesn't have to be replicating faster. The virus can even be replicating slower than antibodies are being produced but, if there was sufficient viral load before the immune system got moving, it took some time to get on top of it. As with all things statistical, the important thing is the mean result of these variables (and also to note that these variables are subject to further variables imposed by parameters in the host; environmental factors, in other words). So let's look at variants briefly, because this is going to matter a lot.

The key thing to measure in any variant is the difference between exposure and positive PCR test - the incubation period. I've covered PCR testing in Testing Times, so I won't do any more on that here, but I do need to mention sampling.

A PCR test will, if a particular DNA sequence is present in the test sample, amplify it. This is an unambiguous true fact about the world.

What it can't do is tell you if, when the sample was taken, the patient was completely virus free. If you think about it, it becomes obvious. When I ram a swab up into your sinus cavity like an ancient Egyptian embalmer evacuating pharaoh's cranium, there's no guarantee that I'm going to come away with a sample of the virus or its RNA. That's part of the reason they scramble it around, to increase the likelihood as much as possible that they get a sample of any infection present. It's statistical, though. If you have only a small sample of the virus attached to cells in a hard-to-reach spot, you can easily get a false negative. The more replication has occurred, the lower the probability of a false negative on a PCR. Still, those are statistical outliers, and what concerns us always is the mean. We can take an aggregate of samples from patients during the first wave with known exposure times and measure the time to a positive PCR test.  For the purpose of this, we can treat a positive test and exhibiting symptoms as being equivalent. They aren't, but the timing isn't sufficiently different to substantially alter the point here. The other important thing about the time to a positive PCR test is that peak infectiousness is reached in the preceding 48 hours. Again, this is a matter of statistics based on replication rate. 

Let's start with Alpha \(\alpha\), because that's the baseline for any comparison that might come up. I don't have further plans immediately for variants, but I've learned the hard way to lay good foundations.

A large sampling of \(\alpha\) patients in 2020 showed a time from exposure to positive PCR with a mean of 5 to 8 days and a peak at 5.61 days. Since \(\alpha\) is our base, we'll set the viral load at time of positive test to 1.[1]  

The most important variant for our purposes is the one currently most prevalent. There are other variants of interest/concern, but the one smashing through the unvaccinated at the moment - and, importantly for our purposes, infecting the vaccinated and those with conferred immunity from first wave infections - is Delta \(\delta\).

One of the first things healthcare workers noticed about \(\delta\) was that people were getting sick much faster. Once similar data were gathered to the \(\alpha\) numbers above, it became pretty obvious why, because the numbers for \(\delta\) were very different. In particular, it showed a mean time of 3 to 5 days with a peak at 3.71. That's a mean of less than 4 days, meaning peak infectiousness can be reached in 2.

Oh, and where we set the viral load at 1 for \(\alpha\)? For \(\delta\) it's 1000. Yep. 1,000 times the viral load at time of positive PCR, meaning infectiousness reached much, much earlier, even if peak infectiousness isn't reached until day two.

So, what does this mean for vaccine passports?

Well, the first thing to note is that our vaccines aren't 100% effective. That's down to several factors, not least of which is this variant isn't the variant the vaccine was aimed at. It's not substantially different than it would have been, because the basic mechanisms are the same, but now we have a faster replication rate and higher viral load, meaning even vaccinated people can get quite sick, even if they don't suffer the same as full, unprotected exposure. 

In a nightclub rammed with 1,000 people, all happily having been vaccinated and grasping their passports, the probability that fewer than one of them is infected is pretty low. The probability, given the presence of at least one infected person, of avoiding a significant number of them becoming infected is also very low. In fact, taking the most basic evolutionary principles into account, the differential in vaccine effectiveness in that one place represents a fitness gradient, increasing the probability of the most dreaded scenario; full vaccine escape.

Either way, the probability of one of these nightclub events leading to the infection of an unvaccinated person is, all things considered, not insignificant.

On their own, then, what vaccine passports will do is provide a false sense of security that will lead to more infections and a higher probability of new variants. I don't want to overstress the probability of new variants arising in this scenario, especially when compared to the lunatic actions of the government in looking like they're trying to generate a viral menagerie, but they're not inconsiderable. That aside, we could combine it with testing, and say a vaccine passport and a negative test. That's not without significant pitfalls.

A PCR test takes anywhere from 24 hours to two days to return. As we've already seen, even discounting the possibility of the sampling error I began with, you can get your swab done, get infected later that day, get your negative PCR test results on day three and go out to a nightclub just as you hit peak infectiousness.

Lateral flow tests are a much quicker option, of course, but quite prone to false negatives. That makes them very useful when used repeatedly over time, but they're not robust enough to have ruled out infection. 

Now, that's not to say that there aren't benefits to vaccine passports. The first and most obvious is the possibility they might encourage otherwise hesitant people to get vaccinated, which is very much a good thing and I encourage any move to that wholeheartedly. Given what's gone before, though, as detailed in recent outings, I'm disinclined to give the government the benefit of any unicorn of doubt in terms of their motivation.

What the vaccine passport does do, in real terms, is provide a comforting allusion to the perfectly reasonable notion that the government cares for your safety. It's hardly surprising now, in a time when almost the entire engagement of society with politics is conducted by dead cat and dog-whistle, that the government are limbering up their Mary Whitehouse routine once again, nor that they're lying. It's pure flim-flam; the instruction to pay close attention to this hand.

It's a super-spreader disguised as benevolent concern.

For these reasons, I oppose them.

[1]MIT Med School comparison

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