I’ve said a few times now that virulence of SARS2 has been increasing steadily since the first Omicron wave.
And so what I want to do today is look at a new analysis, that looks at this subject. It finds what I told you, that every successive Omicron wave has had greater virulence.
I’m not very confident in their methodology however. Specifically, the numbers before Delta look like bunk to me, especially Wuhan. What goes on there is that most cases simply were not diagnosed, there was no mass testing. As a result the CFR looks awfully high.
There are other issues of course too. Omicron’s CFR looks artificially low, because unlike previous variants it’s much better at infecting young people. Wuhan in contrast was the worst variant at infecting a large share of the population, it mostly stuck around infecting the elderly and the sick and as a result its CFR looks inflated, along with the terrible treatment protocol we had at the time (intubation) inflating the death toll.
But all those arguments are hard to apply to the Omicron waves. In fact, because everyone should have some immunity, you’d expect the CFR to go down over time. But it doesn’t. It’s the same problem you see with long COVID. We now have multiple studies, showing reinfections have a higher risk of causing long COVID than the initial infection, because the damage leading to such symptoms builds up over time and the variants become more virulent.
The authors of this study argue that they can extrapolate the trend, resulting in the next major variant being four times deadlier than what we have now:
I personally don’t have much faith in this method of making predictions.
I have much more faith in the mouse passage studies, which show: Absent any sort of specific pressures, virulence steadily increases with time as it moves from one naive mouse to another.
So what sort of pressure reduces virulence? There’s a role to be played for antibodies against virulence associated epitopes, but the main selection against virulence is by NK cells. This has been proven for Influenza.
Most people don’t have proper NK cell immunity because they have antibodies instead, that prohibit NK cells from learning to do their job. In addition to this, the CD8+ T cells learned to kill infected cells, rather than the NK cells. The CD8+ T cells don’t select against virulence either. A CD8+ T cell just looks at whether a cell is expressing a specific antigen. Uniquely, an NK cell checks whether a cell looks healthy or not, as part of its calculation of whether it should kill the cell. And if you let healthy cells live, while killing the sick ones, you cause strains of SARS2 that damage your cells to go extinct, while allowing milder strains to survive.
When everyone has such strong NK cell immunity, we select against virulence. We domesticate this virus and turn it into another hCov. As long as we keep provoking CD8+ T cell immunity and antibodies, we’re not discriminating against virulence. And in the absence of discrimination, the virulent strains better at suppressing Interferon take over.
So that’s why I expect virulence to increase. Right now it looks like the XBB.1.16 strain is failing to cause a wave in the Western world, as the population here developed a strong antibody response from XBB.1.5.
This is not a good thing, it means that it gets time to steadily improve its Interferon suppressing capacity, getting a growing share from a shrinking pie, before it then reaches sufficient fitness to cause the next wave of mass infection.
A new round of vaccination could delay such a wave, if the population goes along, but it would just further enable the stealth evolution of interferon suppressing virulent variants.
The problem is that we have triggered a strong antibody response through mass vaccination, along with a strong CD8 T cell response in the genetic vaccines that transform cells. These antibodies and CD8 T cells can’t select against virulence.
In fact, when you’re deploying CD8 T cells against a virus known to deplete CD8 T cells, you’re simply opening up new roads towards greater virulence. You don’t suffer this problem with the NK cells as they recognise infected cells early.
So to summarise, I agree with the observation of increasing Omicron virulence. In fact their method underestimates the severity of the problem, as they look at observed rather than intrinsic virulence and don’t account for increased immunity and improving treatments.
I don’t think their method of predicting future virulence has any validity though.