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Tag: Omicron

Vaccines, Breakthroughs, and Omicron: A Summary

Graziani, Carlo J. 0 Comments

What Was This Thread About?

I began writing this series of posts as a way of systematizing a number of ideas—some of them mere discomforts—that I’ve been accumulating as I’ve learned to to do technical/statistical/data-driven work in COVID-19 epidemiology over the course of the past year or so. I don’t exactly know what to do with these ideas: not being a trained life scientist, I don’t have a great track record at writing life science papers, and in any event I’m not certain that the things that I’ve discussed in the past few posts could be fit comfortably in a “real” scientific paper. There isn’t a lot of data in what I’ve discussed, for one thing (which makes it a weird thing for a “data scientist” to be trafficking in!). On the other hand, I do think that I have seen a few things that have value, and uncovered some unexamined assumptions that really need to be held up to sunlight. So the best I can think to do for now is blog them, and hopefully get the parts of the ideas that turn out not to be wrong into scientific discussions.

I’ve pretty much emptied the sack at this point, so I’m not planning to keep on writing more of these, unless I notice anything else. What I’d like to do today is draw up a coherent summary of where we stand with respect to breakthroughs, vaccines, Omicron, and the state of epidemic surveillance, drawing on the last four posts.

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How To Detect a Real Vaccine-Escape Variant In Real Time, And Why We May Need To

Graziani, Carlo J. 0 Comments

Genome Dominance And Co-Infection

In my previous post, on Omicron’s actual status in the typology of breakthrough infections, I alluded near the end to a fact that strikes me as requiring much more of an explanation than is usually given. The fact in question is that in the SARS-CoV-2 epidemic, every time a new, rapidly-reproducing variant has burst on the scene, within a few months it has driven all its rival variants clean out of the community-spread genome.

Take a look at The Covariants.org Per-Country page, and let your mouse scroll over the United Kingdom chart—the UK has been consistently sequencing more specimens more assiduously, completely, and regularly and since far earlier than any other nation, as you can see from the number of sequences (the “num seq” pop-up figure), so it’s the best case study. You can see that until 12 October 2020 there was a variant winningly named “EU1” cruising to dominance over its competitors. But on 14 September something new had happened: 3 specimens had turned up with a new variant, named “Alpha”. By 8 March, Alpha has secured 98% of the circulating genome (34648/35670 specimens) and appeared on its way to crushing EU1 (173/35670 specimens), but again, something new had just happened: 6 specimens of a new variant, “Delta” had just shown up. You already know how this story goes: Delta swept the board. By Mid-August, Alpha sightings were as common as Elvis sightings (21/75887), and EU1 sightings were like unicorn sightings (2/75887). In the 1 November data—just prior to Omicron’s appearance—out of 96120 specimens only 9 were not Delta or some cousin of Delta. At that level, to explain the non-Delta signal, we’re really looking at accidents rather than spread: things that interfere with good mixing, such as small, isolated communities perhaps, or travel from distant areas. Natural alternatives to Delta had clearly been driven out of the larger circulating SARS-CoV-2 genome by the time Omicron showed up.

Why?

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Is Omicron A “Vaccine-Escape” Variant?

Graziani, Carlo J. 1 Comment

How Can We Know What Kind Of Breakthrough Infections Omicron Produces?

At the end of my previous post on breakthrough infections I suggested that there are in fact very good reasons to believe that the Omicron variant is not creating “dangerous” (to the patient) breakthrough infections, that is, it is not creating “Type 1 breakthrough infections”, in the typology that I set out in that post. The ability to create Type 1 breakthrough infections would make a variant very dangerous, because an infection by such a variant would evade vaccine-primed human immunity, and the patient’s immune system would have to start from scratch on the time-consuming process of learning to identify the virus, and to create the armament of antibodies and immune cells to fight it without the assistance of a vaccine. The “Type 3” breakthroughs (whether of the “false breakthrough” or “semi-breakthrough” sub-types) are much less dangerous. Neither sub-type actually evades vaccine-primed immune response: they merely appear to, because the rapid reproduction of the virus in the body leads to measurable, often infective levels of viral load despite neutralizing antibodies’ efforts to restrain that growth; but the infection’s early doom is already sealed, because the cellular part of the adaptive immune system—specifically the killer T-cells—are on their way, and will wipe it out in short order. So while the infected individual may be infective (Type 3b), he or she is not usually at risk of severe disease.

This is an orderly proceeding for an immune response to an infection, incidentally. Neutralizing antibodies are only the first layer of the adaptive immune system, and despite their prominence in media discussion of vaccines and therapies they are not responsible for either preventing severe disease or clearing an infection. Antibodies merely slow down the rate of growth of the infection, buying time for the real heavy hitters—the T-Cells—to be mobilized to fight off the infection. That’s the key difference between Type 1 and Type 3: if a variant can create Type 1 breakthroughs, the T-Cells can’t fight it, whereas if it can only create Type 3 breakthroughs, the T-Cells will kick the crap out of it.

So it actually matters what kind of breakthrough infections Omicron is producing, and that’s the reason I’m trying to create some badly-needed clarity in the discussion surrounding the wretchedly ill-chosen term “breakthrough”. What, then, is the evidence that Omicron is not a Vaccine Escape Variant of Concern?

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Omicron and a Typology of “Breakthrough Infections”

Graziani, Carlo J. 0 Comments

What Do You Mean, “Breakthough”?

It’s amazing to me how much damage a badly-chosen scientific term can do, in a high-consequence scientific field such as COVID-19 epidemiology. The term “Breakthrough infection”, which quickly filtered from journal literature on vaccine effectiveness to public media, turns out to be so poorly defined that it even confuses scientific discussions, and when it enters public discourse it engenders mostly misinformation and panic. It is downright daft terminology, which is unfortunately as ineradicable now as the virus itself. In this post, I’d like to at least try to fix it a little, so the damn term can do some useful work for a change.

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